Hyun-Jung Kim

Antioxidative iridoid glycosides and phenolic compounds from Veronica peregrina

Eight iridoid glycosides and four phenolic compounds were isolated from the EtOAc soluble fraction of Veronica peregrina MeOH extract as the radical scavengers for antioxidant activity. The compounds were identified as protocatechuic acid (1), luteolin (2), veronicoside (3), minecoside (4), specioside (5), amphicoside (6), catalposide (7), 6-O-cis-p-coumaroyl catalpol (8), p-hydroxy benzoic acid methyl ester (9), verproside (10), verminoside (11), and chrysoeriol 7-glucuronide (12) by spectroscopic analysis. All compounds except for 1 and 2 were isolated for the first time from this plant. The antioxidant activity was evaluated by the ORAC(Oxygen Radical Absorbance Capacity) assay, which measures scavenging activity against peroxy radicals induced by 2,2′-azobis (2-methoxypropion-amidine) dihydrochloride, and the ORAC value is expressed as relative trolox equivalent. Compounds 2, 4, 5, 6, 8, and 12 exhibited potent antioxidant activity, and compounds 1, 11 had similar activity with trolox, whereas the other compounds showed weaker activity than trolox.

A multifunctional mesoporous nanocontainer with an iron oxide core and a cyclodextrin gatekeeper for an efficient theranostic platform

We report on the dual function of a silica–iron oxide hybrid nanoparticle combined with a stimulus responsive gatekeeper on the surface. Multifunctional hybrid nanoparticles (Fe@Si–DOX–CD–PEG) composed of an Fe3O4 core, a mesoporous silica shell, and GSH-responsive CD gatekeepers are an excellent platform for anticancer drug delivery and MR imaging. In particular, the CD gatekeepers on the surface of the hybrid nanoparticle play a key role in accommodating anticancer drug molecules in the pore of the silica shell without premature release until CD gatekeepers are cleaved by GSH. We confirmed, from an in vitro study with the A549 cell line, that DOX was released from the internalized carriers due to GSH-mediated cleavage of the CD gatekeeper. Consequently, apoptotic and clonogenic death occurred in the cells treated with Fe@Si–DOX–CD–PEG. The accumulation of Fe@Si–DOX–CD–PEG in the tumors was detected by in vivo MR imaging. The growth of the tumor in vivo was effectively suppressed by the intravenously injected Fe@Si–DOX–CD–PEG. In addition, the results of the in vivo MR imaging reflected the in vivo inhibition of the cancer growth by Fe@Si–DOX–CD–PEG.

Effect of BRCA1 Haplotype on Survival of Non–Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy

PURPOSE To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. PATIENTS AND METHODS We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). RESULTS The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 x 10(-5)), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). CONCLUSION These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.

Differential Effect of Polymorphisms of CMPK1 and RRM1 on Survival in Advanced Non-small Cell Lung Cancer Patients Treated with Gemcitabine or Taxane/Cisplatinum

Introduction: To determine whether genetic variations in CMPK1 or RRM1, which impact the pharmacodynamics of gemcitabine, differentially affect the outcomes of non-small cell lung cancer (NSCLC) patients treated with gemcitabine or taxane/cisplatinum. Methods: We conducted retrospective study evaluating the associations between overall survival in 298 NSCLC patients at stages IIIA/IIIB (140) and IV (158), treated with gemcitabine (139) or taxane (159)/cisplatinum and 14 tagging single-nucleotide polymorphisms (tSNPs): 4 in CMPK1 and 10 in RRM1. Results: The wild-type genotypes of CMPK1 IVS1+1057 and IVS1−928 were associated with shorter overall survival in patients treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 1.97 and 1.89; Cox pBonferroni = 0.008 and 0.020), whereas this effect was not observed in patients treated with taxane/cisplatinum. No associations were observed for the other 2 CMPK1 or 10 RRM1 tSNPs. Analysis of the interaction between the CMPK1 and RRM1 genes showed that the survival of patients with CMPK1 IVS1+1057 CC and RRM1 IVS1−2374 TT, IVS7+25 AA, IVS7−425 AA, or IVS8+287 TT was significantly shorter when they were treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 3.00, 2.89, 3.14, and 3.00; Cox pBonferroni = 0.007, 0.012, 0.006, and 0.007). However, these effects were not observed in patients treated with taxane/cisplatinum. Conclusions: These findings suggest that polymorphisms of CMPK1 and their combination with those of RRM1 are helpful in identifying patients who will benefit less from a gemcitabine/cisplatinum as the first-line regimen.

MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma.

We aimed to investigate MYC expression and chromosomal aberration in mantle cell lymphoma (MCL), and the clinical significance of these factors.

Scheduling In-Line Multiple Cluster Tools

A cluster tool which is widely used for wafer fabrication processes consists of several processing modules (PMs), a transport robot, loadlocks, and an equipment front-end module (EFEM) in which a wafer cassette is loaded and unloaded. A wafer cassette with 25 identical wafers is transported by an overhead hoist transfer (OHT) between cluster tools and stored in a stocker when the corresponding tool is not available. Due to a large number of tools and wafer cassettes in a fab, it is extremely complicated to operate OHTs so as to minimize the idle times of the tools. Therefore, fabs tend to reduce the transportation tasks by arranging tools in a line with a buffer. In this paper, we introduce a new system called in-line multiple cluster tools which have many challenging operation issues for researchers and propose simple and practical methods to operate the system. We first develop mixed integer programming models to assign wafers to parallel PMs and derive a priority rule-based scheduling policy for the EFEM operation while minimizing the makespan of producing 25 wafers. We also propose multimode operation in which a component tool in the system processes multiple wafer types at the same time to improve the utilization rate of the tool.

Optimal Scheduling of Transient Cycles for Single-Armed Cluster Tools With Parallel Chambers

Cluster tools, widely used for wafer fabrication processes, have complex scheduling problems because a tool consists of several single-wafer processing chambers and a robot, and has a number of scheduling constraints. Most scheduling studies on cluster tools have focused on steady cyclic cycles where identical work cycles are repeated. However, as the lot size tends to be smaller, a tool has longer noncyclic operation cycles such as the start-up and the close-down. Therefore, we examine a way of scheduling for noncyclic cycles of single-armed cluster tools so as to minimize the makespan. To do this, we first analyse fundamental properties of tool behaviours including noncyclic transient cycles. Using the properties, we identify the workload of processing a lot with a number of wafers. Then, we develop the condition for which the conventional backward sequence, which is known to be optimal for cyclic work cycles, has the optimal makespan. Finally, we develop a linear programming model to find the minimum makespan of the backward sequence.

Schedulability Analysis for Noncyclic Operation of Time-Constrained Cluster Tools With Time Variation

We consider a scheduling problem of a robotized cluster tool for semiconductor manufacturing, which should control wafer delays within a chamber so as not to exceed a specified limit under time variation. The prior research has proposed a p+-time event graph, an extension of Petri nets, for modeling the scheduling problem and developed a method of verifying whether a cyclic p+-time event graph or a cluster tool, which repeats identical work cycles, can satisfy the time constraints under time variation. In this paper, we extend and simplify the schedulability analysis method in the prior research for a noncyclic event graph or a cluster tool which performs start-up and close-down operation for a lot or lot switching, and obtain specialized results. We assume that a robot task sequence or firing sequence of transitions is given. Based on the schedulability analysis, we also propose a way of modifying a not always schedulable noncyclic p+-time event graph with some qualifications to be always schedulable, that is, we prolong token holding times at some places or equivalently delay firings of some transitions so as to be always feasible.

Polysuccinimide Graft Copolymer Nano Aggregates Encapsulating Magnetites for Imaging Probe

AbstractPolysuccinimide (PSI) grafted with methylpoly(ethylene glycol) (MPEG) was synthesized and employed to encapsulate pre-synthesized magnetite using a co-precipitation method. This encapsulation was stabilized by the chemical bonding between PSI and magnetite via the introduction of a bridging compound, 3-aminopropylethoxysilane (APS). The morphology and properties of the magnetite-encapsulated polymer particles were widely characterized to investigate their applications as potential magnetic resonance (MR) imaging probes. The Fourier transform infrared and Fourier transform nuclear magnetic resonance spectroscopy confirmed the successful synthesis of the MPEG-g-PSI- and APS-coated magnetites in addition to X-ray diffraction of their crystalline structure. The size and distribution of the pure and polymer-coated magnetite aggregates were examined using transmission electron microscopy and light scattering analysis. The magnetite-encapsulated aggregates prepared in this study showed excellent superparamagnetic and biocompatible properties that enabled their successful use as MR imaging probes.

Synthesis of an Amphiphilic π-Conjugated Triblock Copolymer of Poly(9,9-didodecylfluorene-2,7-diyl) and Poly(hydroxyl ethyl methacrylate)

A novel amphiphilic, symmetric rod-coil, triblock copolymer (denoted as PHEMA-b-PF-b-PHEMA) of poly(9,9-didodecylfluorene-2,7-diyl) (PF) and poly(hydroxyl ethyl methacrylate) (PHEMA) was synthesized. A π-conjugated poly(9,9-didodecylfluorene-2,7-diyl) (PF) was used as a rodlike midblock segment and connected with hydrophilic end blocks of poly(hydroxyl ethyl methacrylate) (PHEMA) by using an ATRP technique. The chemical structure of PHEMA-b-PF-b-PHEMA was confirmed by 1H-NMR and GPC, and its PL properties were investigated in selected solvents. Due to the dissimilarities in molecular conformation and solubility between PHEMA and PF blocks, both block segments were segregated to display a phase-separated morphology on a Si wafer.