• EDISON SW 활용 경진대회 논문집
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• 제3회(2014년)
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• pp.237-249
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• 2014

Deposition of amyloid-${\beta}$ ($A{\beta}$) proteins is the conventional pathological hallmark of Alzheimer's disease (AD). The $A{\beta}$ protein formed from the amyloid precursor protein is predominated by the 40 residue protein ($A{\beta}40$) and by the 42 residue protein ($A{\beta}42$). While $A{\beta}40$ and $A{\beta}42$ differ in only two amino acid residues at the C-terminal end, $A{\beta}42$ is much more prone to aggregate and exhibits more neurotoxicity than $A{\beta}40$. Here, we investigate the molecular origin of the difference in the aggregation propensity of these two proteins by performing fully atomistic, explicit-water molecular dynamics simulations. Then, it is followed by the solvation thermodynamic analysis based on the integral-equation theory of liquids. We find that $A{\beta}42$ displays higher tendency to adopt ${\beta}$-sheet conformations than $A{\beta}40$, which would consequently facilitate the conversion to the ${\beta}$-sheet rich fibril structure. Furthermore, the solvation thermodynamic analysis on the simulated protein conformations indicates that $A{\beta}42$ is more hydrophobic than $A{\beta}40$, implying that the surrounding water imparts a larger thermodynamic driving force for the self-assembly of $A{\beta}42$. Taken together, our results provide structural and thermodynamic grounds on why $A{\beta}42$ is more aggregation-prone than $A{\beta}40$ in aqueous environments.

• The Korean Journal of Physiology and Pharmacology
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• 제13권4호
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• pp.273-279
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• 2009

The accumulation of ${\beta}$-amyloid (A${\beta}$) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit A${\beta}$ aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of A${\beta}$ depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of A${\beta}$, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of A${\beta}_{1-40}$ molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited A${\beta}_{1-40}$ aggregation and significantly protected SH-SY5Y cell line against A${\beta}_{1-40}$ aggregates-induced neurotoxicity. In details, we examined the effects of citrate on A${\beta}_{1-40}$ aggregation and on A${\beta}_{1-40}$ aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited A${\beta}_{1-40}$ aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in A${\beta}_{1-40}$ alone). In cytotoxicity and viability assays, citrate reduced the toxicity of A${\beta}_{1-40}$ in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with A${\beta}_{1-40}$ aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the A${\beta}_{1-40}$ aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed A${\beta}_{1-40}$ aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit A${\beta}_{1-40}$ aggregation and protect neurons from the apoptotic effects of A${\beta}_{1-40}$ aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.

• 한국토양비료학회지
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• 제4권1호
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• pp.55-66
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• 1971

가. 토양(土壤)의 전(全) ${\beta}$ 방사능(放射能)을 측정(測定)하여 전(全) ${\beta}$ 방사능(放射能) 중(中)에서 $^{40}K$의 기여(奇與)를 $^{40}K$의 ${\beta}$ 선(線) 포화(飽和) 방사능비율(放射能比率)을 사용(使用)하여 전(全) ${\beta}$ 선(線) 분석(分析)을 시도(試圖)한 결과(結果) 답토양(畓土壤)의 전(全) ${\beta}$ 방사능(放射能)은 $^{40}K$의 ${\beta}$ 방사능(放射能)에 기곤(起困)함을 알았다. 따라서 답(畓) 토양(土壤)의 전(全) ${\beta}$ 방사능(放射能)을 측정(測定)한다는 것은 실(實)은 $^{40}$의 ${\beta}$ 방사능(放射能)을 측정(測定)하는 것이다. 나. 전(全) ${\beta}$ 방사능(放射能)으로 부터 $^{40}K$의 핵종(核種) 동정(同定)을 행(行)하는 순서(順序)는 임의시료량(任意試料量)의 방사능측정(放射能測定)와 $^{40}K$의 포화(飽和) 방사능(放射能) 비율(比率)로 계산(計算)한 계산치(計算値)((4)식(式)에서 $G(t){\cdot}A_{\infty}$ 또는 A/G(t))와 비교(比較)하여 일치(一致)되는지를 Chauvenet 기준(基準) 따라서 검정(檢定)한다. 만약에 일치(一致)하지 않을 경우에는 $^{40}K$ 외(外)의 다른 핵종(核種)의 기여(寄與)를 의미(意味)하며 (7)식(式)에 의(依)하여 $^{40}K$과 다른 핵종(核種)을 분별(分別)하여 각각의 방사능(放射能) 붕양율(崩壤率)을 구(求)할 수 있다. 다. 한국(韓國) 답(畓) 토양(土壤)의 $^{40}K$ ${\beta}$ 방사능(放射能)은 $17.5{\sim}44.6{\mu}{\mu}ci/gr$. soil 사이에 있으며 이를 다시 모암(母岩) 별(別)로 보면 석회암(石灰岩)>화강암(花崗岩)>편암(片岩)>편마암(片麻岩)>반암(斑岩)>현무암(玄武岩)>섬녹암(閃綠岩)의 순(順)이다.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.343-347
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• 2014

The present study investigated the effects of Vaccinium uliginosum L. (bilberry) on the learning and memory impairments induced by amyloid-${\beta}$ protein ($A{\beta}P$) 1-42. ICR Swiss mice were divided into 4 groups: the control ($A{\beta}40$-1A), control with 5% bilberry group ($A{\beta}40$-1B), amyloid ${\beta}$ protein 1-42 treated group ($A{\beta}1$-42A), and $A{\beta}1$-42 with 5% bilberry group ($A{\beta}1$-42B). The control was treated with amyloid ${\beta}$-protein 40-1 for placebo effect, and Alzheimer's disease (AD) group was treated with amyloid ${\beta}$-protein 1-42. Amyloid ${\beta}$-protein 1-42 was intracerebroventricular (ICV) micro injected into the hippocampus in 35% acetonitrile and 0.1% trifluoroacetic acid. Although bilberry added groups tended to decrease the finding time of hidden platform, no statistical significance was found. On the other hand, escape latencies of $A{\beta}P$ injected mice were extended compared to that of $A{\beta}40$-1. In the Probe test, bilberry added $A{\beta}1$-42B group showed a significant (P<0.05) increase of probe crossing frequency compared to $A{\beta}1$-42A. Administration of amyloid protein ($A{\beta}1$-42) decreased working memory compared to $A{\beta}40$-1 control group. In passive avoidance test, bilberry significantly (P<0.05) increased the time of staying in the lighted area compared to AD control. The results suggest that bilberry may help to improve memory and learning capability in chemically induced Alzheimer's disease in experimental animal models.

• 대한기계학회논문집A
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• 제38권4호
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• pp.371-377
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• 2014

조직 공학에 있어 인공지지체는 손상된 조직 및 기관의 기능을 재생하기 위한 거푸집으로 제공되며 3 차원 구조물이다. 인공지지체의 재료 중에서 폴리카프로락톤(Polycaprolactone, PCL)과 삼인산칼슘(${\beta}$-tricalcium phosphate, ${\beta}$-TCP)은 생분해성과 생체적합성을 가지고 있다. 본 연구에서는 다축 인공지지체 제작 시스템을 이용하여 3 차원 PCL, blended PCL(60 wt %)/${\beta}$-TCP(40 wt %), 그리고 ${\beta}$-TCP 인공지지체를 제작하였다. 제작된 인공지지체는 주사전자현미경 분석을 통해 $600{\pm}20{\mu}m$의 공극 크기로 잘 제작되었다. 기계적 특성 평가를 통해 3 차원 PCL, blended PCL(60 wt %)/${\beta}$-TCP(40 wt %), 그리고 ${\beta}$-TCP 인공지지체의 효과는 분석되었다. 게다가 Saos-2 세포를 이용한 in vitro 연구를 수행하여 세포 증착 및 증식과 같은 세포 거동에 의한 3 차원 인공지지체의 효과를 확인하였다. 요컨대 3D blended PCL(60 wt %)/${\beta}$-TCP(40 wt %) 인공지지체가 압축 강도와 생체적합성 그리고 골전도성에 있어서 인체의 해면골에 더욱 적합하였다. 따라서 3D 인공지지체의 제작에 있어 PCL과 ${\beta}$-TCP를 혼합하는 것은 효과적인 골 재생을 위해 촉망되는 전략이 될 것이다.

• EDISON SW 활용 경진대회 논문집
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• 제5회(2016년)
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• pp.55-61
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• 2016

$A{\beta}_{40}$ peptides form oligomers that later aggregate into a plaque, which is deemed to be a leading cause of Alzheimer's Disease. Its non-crystalline morphology has limited an understanding of comprehensive structural study. In this research, computational biomolecular simulations were performed in the following order: solvent and ion addition in a box, energy minimization of protein, equilibration, and periodic boundary condition disaggregation of a monomer from fibril. The result founded the two-fold model is 25% more stable in the simulation environment, and the steric zippers held on most tightly until 220 ps of simulation. The study supports the previous findings that two-fold aggregate $A{\beta}_{40}$ is more stable at 310 K and discusses further how much contribution steric-zipper and hydrogen bonding are making.

• 한국식품과학회지
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• 제22권2호
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• pp.134-139
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• 1990

누룩으로부터 ${\beta}-galactosidase$ 활성을 가지는 균주를 순수분리하여 분리된 균주(NY-15)의 ${\beta}-galactosidase$를 정제하였다. 다량배양하여 모은 균체를 8%(v/v) toluene 처리에 의한 추출액을 정제의 출발 물질로 하여 acetone 침전에 의해서 탈지처리를 한 후 40-60%포화의 ammonium sulfate 분획을 하고 DEAE-cellulose, DEAE-Sephadex A-50의 이온교환 chromatography를 한 후 Agarose-PAPT를 이용한 affinity chromatography에 의해서 정제하였다. 이 정제법에 의해서 ${\beta}-galactosidase$는 조효소 추출액으로부터 40배 정제되었으며 회수율은 7.7%였나. 누룩 yeast의 ${\beta}-galactosidase$는 2개의 subunit로 되어 있으며, 각 subunit 분자량은 각각 96,000과 130,000이었다. 효소활성에의 최적 pH는 7.5이었고, 최적온도는 $40^{\circ}C$이었다.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Spring Conference
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• pp.75-90
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• 2006

Both synthetic and endogenous $A{\beta}$ are degraded by peptidase G. Both $A{\beta}40$ and 42 are cleaved by peptidase G. Peptidase G cleaves $A{\beta}40$ into small fragments ($A{\beta}18$) which lacks aggregation property and are not toxic to neuron. Peptidase G seems to degrade multimeric $A{\beta}$ more efficiently than monomeric $A{\beta}$. Peptidase G protects neurons from toxicity induced by $A{\beta}$ by cleaving it into smaller fragments. Thus, dis-regulation of peptidase G could contribute amyloid deposit found in AD brain.

• 대한수학회보
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• 제40권4호
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• pp.649-661
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• 2003

The ($\alpha,\;\beta$)-metric is a Finsler metric which is constructed from a Riemannian metric $\alpha$ and a differential 1-form $\beta$. In this paper, we discuss the projective flatness of Finsler spaces with certain ($\alpha,\;\beta$)-metrics ([5]) in a locally Minkowski space.

• EDISON SW 활용 경진대회 논문집
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• 제4회(2015년)
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• pp.14-23
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• 2015

Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.