• 한국환경보건학회지
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• 제39권2호
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• pp.130-137
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• 2013

Objectives: The OECD QSAR Application Toolbox was developed by the Organisation for Economic Cooperation and Development (OECD) to facilitate the practical use of QSAR approaches in regulatory contexts as well as to reduce the need for additional animal testing. In this study, human health and the ecotoxicity of chemicals were predicted by applying the OECD QSAR Application Toolbox and the results were compared with experimental data in order to evaluate the applicability of this program. Methods: Read-across, trend analysis, and QSAR of OECD QSAR Application Toolbox were used for the prediction of toxicity. Results: The toxicity prediction was conducted on 6,354 chemicals for which toxicity data have been produced on the six endpoints of skin sensitization, skin irritation, eye irritation, mutagenicity, and acute toxicities of fish and Daphnia. From the total of 6,354, we obtained prediction results for 1,621 chemicals (25.5%). Conclusions: The predicted properties of mutagenicity, skin sensitization, and acute aquatic toxicities were reasonably good when compared with experimental data, but other endpoints were not due to the limitation of applicable chemical groups.

• Safety and Health at Work
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• 제2권2호
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• pp.105-121
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• 2011

Objectives: This paper presents the framework and protocol design for a construction industry risk management toolbox. The construction industry needs a comprehensive, systematic approach to assess and control occupational risks. These risks span several professional health and safety disciplines, emphasized by multiple international occupational research agenda projects including: falls, electrocution, noise, silica, welding fumes, and musculoskeletal disorders. Yet, the International Social Security Association says, "whereas progress has been made in safety and health, the construction industry is still a high risk sector." Methods: Small- and medium-sized enterprises (SMEs) employ about 80% of the world's construction workers. In recent years a strategy for qualitative occupational risk management, known as Control Banding (CB) has gained international attention as a simplified approach for reducing work-related risks. CB groups hazards into stratified risk 'bands', identifying commensurate controls to reduce the level of risk and promote worker health and safety. We review these qualitative solutions-based approaches and identify strengths and weaknesses toward designing a simplified CB 'toolbox' approach for use by SMEs in construction trades. Results: This toolbox design proposal includes international input on multidisciplinary approaches for performing a qualitative risk assessment determining a risk 'band' for a given project. Risk bands are used to identify the appropriate level of training to oversee construction work, leading to commensurate and appropriate control methods to perform the work safely. Conclusion: The Construction Toolbox presents a review-generated format to harness multiple solutions-based national programs and publications for controlling construction-related risks with simplified approaches across the occupational safety, health and hygiene professions.

• 한국환경보건학회지
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• 제45권5호
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• pp.457-464
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• 2019

Objectives: Quantitative structure-activity relationship (QSAR) is one of the effective alternatives to animal testing, but its credibility in terms of toxicity prediction has been questionable. Thus, this work aims to evaluate its predictive capacity and find ways of improving its credibility. Methods: Using $TOPKAT^{(R)}$, OECD toolbox, and $Derek^{(R)}$, all of which have been applied world-wide in the research, industrial, and regulatory fields, an analysis of prediction credibility markers including accuracy (A), sensitivity (S), specificity (SP), false negative (FN), and false positive (FP) was conducted. Results: The multi-application of QSARs elevated the precision credibility relative to individual applications of QSARs. Moreover, we found that the type of chemical structure affects the credibility of markers significantly. Conclusions: The credibility of individual QSAR is insufficient for both the prediction of chemical toxicity and regulation of hazardous chemicals. Thus, to increase the credibility, multi-QSAR application, and compensation of the prediction deviation by chemical structure are required.

• 자원환경지질
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• 제40권4호
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• pp.419-443
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• 2007

최근 국내에서는 외국기업의 국내진출에 따른 M&A, 미국과의 자유무역협정에 따른 시장개방에 따라 부지환경평가 (토양환경평가)의 결과를 반영할 필요성이 점차 증가되어 왔다. 따라서 이 연구에서는 연안매립지역에 위치한 대규모 화학공장부지에 대한 실제적인 부지환경평가를 통하여 국내의 토양환경평가 지침의 문제점을 보완하고 효율적, 경제적 평가를 위한 복합적 조사기법들을 이용하였다. 이 연구는 기초조사, 부지현황조사, 시료채취와 분석, 관측정 설치와 수리지질 조사, 자료 분석의 6단계로 진행되었다. 각각의 조사단계에서는 기존자료조사, 선구조분석, 지표지질조사, 지구물리탐사, 시추조사, 수리전도도, 지하수의 유향유속측정, 시료채취 및 분석 결과를 조합하여 복합적으로 해석하였다. 연구결과, 부지환경평가를 위한 이러한 다양한 조사기법들의 적용은 부지의 오염현상, 지하매질에 대한 부지특성화에 매우 효과적이었다. 국내에서는 '토양환경평가 지침'에 의한 기초조사에 있어 기존자료의 이용, 가용한 자료의 보관상태, 평가를 위한 관계자 인터뷰 등에 있어 매우 열악한 여건을 가지고 있다. 따라서 '부지환경평가'를 수행하는데 있어 이러한 복합조사기법의 적용은 더욱 경제적이고 효율적이며, 토양과 지하수오염을 연계하여 평가하는데 있어서도 매우 유용할 것으로 기대된다.

• Interdisciplinary Bio Central
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• 제3권1호
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• pp.3.1-3.16
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• 2011

Investigation of the genetic functions in complex biological systems is a challenging step in recent year. Hence, several valuable and interesting research projects have been developed with novel ideas to find out the unknown functions of genes or proteins. To validate the applicability of their novel ideas, various approaches are built up. To date, the most promising and commonly used approach for discovering the target proteins from biological system using small molecule is well known a forward chemical genetics which is considered to be more convenient than the classical genetics. Although, the forward chemical genetics consists of the three basic components, the target identification is the most challenging step to chemical biology researchers. Hence, the diverse target identification methods have been developed and adopted to disclose the small molecule bound protein. Herein, in this review, we briefly described the first two parts chemical toolbox and screening, and then the target identifications in forward chemical genetics are thoroughly described along with the illustrative real example case study. In the tabular form, the different biological active small molecules which are the successful examples of target identifications are accounted in this research review.

• Korean Chemical Engineering Research
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• 제54권5호
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• pp.621-629
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• 2016

EU의 REACH 제도 도입에 따라 각종 화학물질에 대한 독성 및 활성 정보 확보를 위해 화학물질의 분자구조 정보를 기반으로 화학물질의 독성 및 활성을 예측하는 정량적구조활성관계(QSAR)에 대한 연구가 최근 활발히 진행되고 있다. QSAR 모델에 사용되는 분자표현자는 매우 다양하기 때문에 화학물질의 물성 및 활성을 잘 표현할 수 있는 주요한 분자표현자를 선택하는 과정은 QSAR 모델 개발에 있어 중요한 부분이다. 본 연구에서는 화학물질의 분자구조 정보를 나타내는 주요 분자표현자의 통계적 선택 방법과 부분최소자승법(Partial least square: PLS) 기반의 새로운 QSAR 모델을 제안하였다. 제안된 QSAR 모델은 130종의 폴리염화바이페닐(Polychlorinated biphenyl: PCB)에 대한 분배계수(log P)와 14종의 PCBs에 대한 반수 치사 농도(Lethal concentration 50%: $LC_{50}$) 예측에 사용되고, 제안된 QSAR 모델 예측 정확도는 기존의 OECD QSAR Toolbox에서 제공하는 QSAR 모델과 비교하였다. 관심 화학물질의 분자표현자와 활성정보 간의 높은 상관관계를 갖는 주요 분자표현자를 선별하기 위해서, 상관계수(r)와 variable importance on projections (VIP)기법을 적용하였으며, 화학물질의 독성 및 활성정보를 예측하기 위해 선별된 분자표현자와 활성정보를 이용해 부분최소자승법(PLS)를 사용하였다. 회귀계수($R^2$)와 prediction residual error sum of square (PRESS)을 이용한 성능평가결과, 제안된 QSAR 모델은 OECD QSAR Toolbox의 QSAR 모델보다 PCBs의 log P와 $LC_{50}$에 대하여 각각 26%, 91% 향상된 예측력을 나타내었다. 본 연구에서 제안된 계산독성학 기반의 QSAR 모델은 화학물질의 독성 및 활성정보에 대한 예측력을 향상시킬 수 있고 이러한 방법은 유독 화학물질의 인체 및 환경 위해성 평가에 기여할 것으로 판단된다.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2002년도 학술발표대회
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• pp.18-25
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• 2002

The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.

• 마케팅과학연구
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• 제19권3호
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• pp.49-61
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• 2009

本文为执行官提供了他们在处理日常业务问题和市场机会时如何阐述自己思考过程的培训. 本研究建立在Schank提出的教学基础上, 包括: (1)经验学习和最好的指导提供给学习者从诸如全球背景, 团队项目和专家经历等的互动的故事提炼知识和技能的机会. (2) 告诉不会导致学习, 因为在学习需要的行动训练环境中, 应强调积极使用故事, 案例和项目. 每个培训案例包括执行官解释自己的决策系统分析(DSA, 还需要执行官做DSA简报. 在训练时要求执行官写DSA简报. 在执行官学员写书面报告的说明中包括(1) DSA路线图的本质的细节(2) 警告和机会的陈述, 读者的行政地图及图内的DSA解释. 该报告的最大长度为500字, 其规则就是使行政人员培训课程行之有效. 引言之后是第二部分文献综述, 简要地总结了有关人们在对问题和机会的背景下的想法及文献. 第三部分通过使用对不同的贴牌生产客户定价相同的化学产品的培训练习来解释DSA的起源和过程, 第四部分展示一个炼油设备公司订价决策的培训练习. 第五部分提供一个商业客户办公家具采购的市场策略案例. 第六部分是结论和建议. 这些建议是关于使用培训课程和发展其他培训课程来磨练执行官制定决策的能力. 文章引导读者利用工具箱研究综合的报告, (DSA)路线图根据生态合理性理论将战略与环境相匹配. 这三个案例的研究让学习者在意愿层面征求建议来作出决策. Todd and Gigerenzer 提出人们使用简单启发式,因为他们在自然的决策环境中通过探索信息的结构使适应性行为有可能产生. "简单是一种美德, 而不是诅咒", 有限理性理论强调了西蒙的命题中心, "人类理性的行为仿佛一把剪刀, 其刀片则是任务环境的结构和执行者的计算能力". Gigerenzer的观点和西蒙的环境的危害相关, 也和本文中三个环境结构的案例相关. "环境这个词, 在这里, 并不是指总的物理和生理的环境, 而只是指被给予需要和目标的重要有机体 本文关注了结合任务环境的结构和使用适应的工具箱启发的报告. (DSA)路线图根据生态理性理论将战略与环境相匹配. 渴望适应理论是这一方针的核心. 渴望适应理论将决策制定作为一个没有把目标整合的多目标问题模拟成一个把所有决策选项进行完全的优先顺序化. 这三个案例研究让学习者在意愿层面征求建议来作出决策. 渴望适应用一系列的调整步骤的形式. 一个调整步骤通过仅一个目标变量的变化就可以改变在渴望网格上邻近点当前的渴望水平. 上调步骤是目标变量的提高, 下调步骤是目标变量的下降. 创造和使用渴望适应水平是对有限理性理论的整合. 文章通过提供学习者经验和实践环节增加了意愿采纳和有限合理性的理解和特点. 利用DSA图排列CTSs和撰写TOP可以清晰和深化Selten的观点 "清晰, 意愿采纳必须作为研究的解决方案整合到整个蓝图中". 这些有限理性的研究许可了在现实生活中为什么, 如何作决策的理论和在自然的环境中利用启发式的学习训练两方面的发展. 本文中的练习鼓励根据不同使用目的学习快速而简洁的启发式技巧和原则. 这也正回应了Schank的思想 "从本质上来看, 教育不是让学生们知道发生了什么, 而是让他们感受到所发生的事情. 这不容易做到. 在如今的学校教育是没有情感的, 这是一个很大的问题". 这三个案例和附加的练习问题遵守了Schank的观点. "这种教育过程最好是通过参与他们其中来实现, 也可以这样认为, 精神层面的积极讨论".