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      • Methane Mitigation from Ruminants by Feed Additives in the trials of In Vitro and In Vivo Using the Automated Head Chamber

        Ashraf Ali Biswas The Graduate School Sunchon National University 2016 국내박사

        RANK : 247375

        EXPERIMENT I : This study was conducted to evaluate the effects of feeding supplemental illite to Hanwoo steers on methane (CH4) emission and rumen fermentation parameters. An in vitro ruminal fermentation technique was conducted using a commercial concentrate as substrate and illite was added at different concentrations as treatments: 0%, 0.5%, 1.0%, and 2.0% illite. Total volatile fatty acids (VFA) were different (p<0.05) at 24 h of incubation where the highest total VFA was observed at 1.0% of illite. Conversely, lowest CH4 production (p<0.01) was found at 1.0% of illite. In the in vivo experiment, two diets were provided, without illite and with addition of 1% illite. An automated head chamber (GreenFeed) system was used to measure enteric CH4 production. Cattle received illite supplemented feed increased (p<0.05) total VFA concentrations in the rumen compared with those fed control. Feeding illite numerically decreased CH4 production (g/d) and yield (g/kg DMI). Rumen microbial population analysis indicated that the population of general 29 bacteria, protozoa, and methanogens were lower (p<0.05) for illite compared with the control. Accordingly, overall results suggested that feeding a diet supplemented with 1% illite can have positive effects on feed fermentation in the rumen and enteric CH4 mitigation in beef cattle. EXPERIMENT II The studies were conducted to evaluate the effects of garlic powder-allicin mixture in cattle on rumen fermentation, and methane emissions in vitro and in vivo. There were two diets, one was without garlic powder-allicin mixture (control) and another was in addition of garlic powder-allicin mixture at 0.1% inclusion rate (T1). Commercial late fattening concentrate pellet feed (1%) on dry matter (DM) basis was used as substrates for in vitro rumen fermentation. In this experimental trial, in vitro result showed that garlic powder-allicin mixture supplemented diet contributes significantly (p<0.05) higher butyric acid and lower methane (CH4) production at 24 h of incubation period but no significant difference was observed in pH, total gas, acetic acid, propionic acid, acetic acid/propionic acid (A/P) ratio and total volatile fatty acid (VFA). The in vivo experiment was conducted using automated head chamber (GreenFeed). In case of in vivo experiment with GreenFeed, higher value of acetate was observed in garlic powder-allicin mixture supplemented diet but no significant difference was observed on propionate, butyrate, total VFA with CH4. Though there was significantly higher total bacterial DNA copies of garlic powder-allicin mixture group but there were no significant difference of protozoal and methanogens DNA copies. Therefore it is presumed that 0.1% garlic powder-allicin mixture has no effect on productivity and CH4 reducing potentiality. EXPERIMENT III This study was conducted to determine the effect of lysozyme addition on in vitro rumen fermentation and to identify the lysozyme inclusion rate for abating methane (CH4) production. An in vitro ruminal fermentation technique was done using a commercial concentrate to rice straw ratio of 8:2 as substrate. The following treatments were applied wherein lysozyme was added into 1 gm dry matter (DM) substrate at different levels of inclusion: without lysozyme, 2000, 4000, and 8000 U lysozyme. Results revealed that lysozyme addition had a significant effect on pH after 24 h of incubation with the highest pH (p<0.01) observed in 8000 U lysozyme, followed by the 4000 U, 2000 U, and without lysozyme. The highest amounts of acetic acid, propionic acid (p<0.01) and total volatile fatty acid (TVFA) (p<0.05) were found in 8000 U after 24 h of incubation. The CH4 concentration was the lowest in the 8000 U and the highest in the without lysozyme addition after 24 h of incubation. There was no significant differences in general bacteria, methanogen, or protozoan DNA copy number. So far, addition of lysozyme increased the acetate, propionate, TVFA, and decreased CH4 concentration. These results suggest that lysozyme supplementation may improve in vitro rumen fermentation and reduce CH4 emission.

      • A Study on the Selection of Container Ports in Egypt's East Mediterranean Sea using Fuzzy-AHP

        Ahmed Ashraf Abdelfattah Mahmoud 순천대학교 대학원 2021 국내박사

        RANK : 247374

        The aim of this study is to examine a comparative assessment of criteria for container ports at four major container ports in Egypt’s Mediterranean Sea which are Alexandria, Al Dekheila, East Port-Said and Damietta. From previous studies personal “online” interviews and questionnaires, completed by top shipping companies, freight forwarders, logistics service providers and experts in Egypt, important container port selection criteria are established and comparisons between container ports are made. The theoretical hierarchy to validate the study model and the hypothesis process (AHP) system, in which attributes of scale are used to classify which port selection criteria are best for which ports are used and to pick the most suitable container port from the selected ports in Egypt’s Mediterranean Sea. This paper's other goal is to weigh the most dominant selection Analytic Hierarchy Method (AHP) collection of container port requirements. In 38 survey forms were distributed, 26 were returned, and 12 were not completed. And have therefore been discarded. CEOs or equivalents, senior managers and port masters (or) business managers, or similar ranks, were the 26 survey participants. Of the interview participants, 23 (88%) had five or more years of service. High-level expertise in the business related to shipping and logistics. Three (12%) of the respondents have at least 3 years of experience working in the industry. The first results indicate that the weight and priority vector figure of it can be shown that port efficiency has achieved the five primary requirements, the highest priority criterion, with port costs as the second priority. The geographical location requirements and accessible port facilities are the third and fourth most relevant, respectively, and the port hinterland is the last priority component. The significant factors among the 11 influential factors that could influence the choice of hub ports are: “port charges/ terminal handling charges/ pilotage/ towage”, “vessel turnaround time”, “depth of port” and “container handling equipment and CY & backup facilities”. They are followed by “near to the feeder port”, “close to the import/export area, “custom quality”, “ICD, free trade zone, and “Inter-modal link (rail, highway, and barge). Connectivity to rail, road installations “and” inland transshipment freight prices “are the least desirable components”. With respect to the relative rivalry between these ports, out of five factors, excluding the port hinterland, East Port-Said port obtained the highest priority in four influential factors for regional hub port choice. Alexandria, which has acquired the most important priority factors in port hinterland connectivity and second position in the other four factors, has a second priority. In all parameters, Damietta Port is the third priority rank and in all influential elements, Al Dekheila Port is the least priority place. In this analysis, there are certain limitations which will require future studies. First, the population-size sample group is relatively small. Better results could be given by a larger sample. Second, interviewees had limited experience responding to questionnaires using this technique in this sample, and there was a limited amount of time available for interviews per respondent. Lastly, applying a cost-benefit forecasting analysis to the outcome of possible potential regional hub ports might be a smart idea. Another objective of this study is proposing a method of performance measurement using the Fuzzy Analytic Hierarchy Process (FAHP) approach to determine the efficiency level of container ports. To show the applicability of the proposed structure, an empirical study was performed on Egypt’s Mediterranean container ports for the period from 2015 to 2019. More complex approaches by complementing the limits of this analysis further analysis is recommended with further data collection work to obtain further information and more convincing findings.

      • Development and implementation of a sympathetic decision model for renewable energy integrated power systems

        Ashraf, Hafiz Muhammad Sungkyunkwan University 2024 국내박사

        RANK : 247359

        Climate change has a perceptible effect on the forecasting of renewable energy sources (RES). Because of the COVID-19 pandemic, the global weather showed diverted behavior from its normal data. In such situations, the forecasting of RES has become extremely challenging. To predict the level of uncertainty and its impact is also quite difficult. Probabilistic and statistical approaches to deal with this issue require huge amounts of data for the prediction and further planning of power system sources. It has been found that Information Gap Decision Theory (IGDT) found a better and more efficient alternative to deal with uncertainty. So, uncertainty is modeled with only available data and unknown data is predicted. Due to the rapid growth of the population and their needs has been a great rise in electrical demand. In this way the load is also uncertain and must predict the expected change. If the voltage of the power system is considered as the stability factor, then impact of RES output power sources must be found on spatial and temporal bases. Uncertainty modeling and prediction of expected RES and load values are considered as the first goal. About the planning and scheduling of RES and loads, it is better to set the second major goal to find the impact of RES and loads with the help of a sensitivity analysis (SA) technique. In this research the uncertainty level prediction is attained by making classes of the observed uncertainty based on the robust and opportunity concept of IGDT. Artificial Neural Networks (ANN) technique is found useful to find the class of uncertainty based on the large number of data provided at the training stage. Although many SA techniques have been found but the Rosenblatt based multivariate global sensitivity analysis (RMV-GSA) is found quite different and effect due to its simple use. For the application, RMV-GSA input and output correlation and impact data considering the voltage stability limit is also used for the training of ANN. Then a decision model is developed by deciding set of results obtained from IGDT and RMV-GSA through ANNs. This decision model is built on the Sympathetic impact concept of IGDT, that is why it is named the sympathetic decision model (SDM). The SDM helps to schedule or reschedule the RES input power to the power system and load connection. First the proposed model has been applied to the IEEE 30 and IEEE 123 bus test systems for the uncertainty modeling classification and quantification to support the penetration of RES along with the load rescheduling. The proposed SDM model performed in a very satisfactory manner which did not achieve the above-mentioned goals but also mitigated the voltage unbalance as per IEEE 1547 voltage standard for RES integration. Moreover, the proposed SDM model is also applied to deal with the economic dispatch and unit commitment for the IEEE 30 bus test system. For the successful implementation, the proposed SDM model has been embedded with the reinforcement learning (RL) algorithm as SDM-RL agent. Deep Deterministic Policy Gradient (DDPG) Agent has been chosen here as an RL agent. RL agent further improved the impact of proposed SDM to the applications for the RES integrated power systems. In Summary, the proposed methodology has five main parts; 1) Uncertainty classification using IGDT 2) Impact of RES and loads using RMV-GSA 3) Training the ANNs based on the results of 1) and 2), 4) Decision model formation: making decision set parameters obtained results from IGDT and RMV-GSA through DNN and decision about scheduling or rescheduling of RES and loads 5) The proposed SDM model embedded to apply for the UCED case. Application of the proposed methodology has shown a great impact in stabilizing voltage, penetration of RES, load adjustment thermal power economic dispatch. 기후 변화는 재생 에너지원(RES) 예측에 상당한 영향을 미칩니다. 코로나19 팬데믹으로 인해 전 세계 날씨는 정상적인 데이터와 다른 양상을 보였습니다. 이러한 상황에서는 RES의 출력을 예측하는 것이 매우 어려워졌습니다. 불확실성의 수준과 그 영향을 예측하는 것 또한 매우 어렵습니다. 이 문제를 해결하기 위한 확률적 및 통계적 접근 방식은 전력 시스템 내 발전원의 예측 및 계획을 위해 방대한 양의 데이터를 필요로 합니다. 정보 격차 의사 결정 이론(IGDT)은 불확실성을 처리하는 더 나은 효율적인 대안을 발견했습니다. 따라서 불확실성을 다루기 위해 이용 가능한 데이터로만 모델링하였으며 알려지지 않은 데이터는 예측을 통해 구성하였습니다. 인구의 급속한 증가와 그로 전력 수요가 크게 증가하였으며 부하량도 불확실성을 지니게 되고 예상되는 변화를 예측해야 합니다. 전력 시스템의 전압을 안정도 계수로 고려한다면, 공간적 및 시간적 기반에서 RES 출력 전원의 영향을 찾아야 합니다. 불확실성 모델링과 예상 RES 및 부하 값의 예측이 첫 번째 목표로 고려됩니다. RES 및 부하의 계획 및 스케줄링과 관련하여 민감도 분석(SA) 기법을 사용하여 RES 및 부하의 영향을 찾는 것이 두 번째 주요 목표로 설정하는 것이 좋습니다. 이 연구에서 불확실성 수준 예측은 IGDT의 견고성 및 기회 개념을 기반으로 관찰된 불확실성의 클래스를 만들어 달성합니다. 인공신경망(ANN) 기법은 훈련 단계에서 제공되는 많은 데이터를 기반으로 불확실성의 클래스를 찾는 데 유용합니다. 많은 SA 기법이 발견되었지만, 로젠블라트 기반의 다변량 글로벌 민감도 분석(RMV-GSA)은 사용이 간편하여 그 효과는 상당히 다른 것으로 밝혀졌습니다. 적용을 위해 전압 안정성 한계를 고려한 RMV-GSA입력 및 출력 상관관계와 영향 데이터를 ANN의 학습에도 사용합니다. 그런 다음 IGDT와 RMV-GSA에서 얻은 결과 집합을 ANN을 통해 결정하여 의사결정 모델을 개발합니다. 이 의사 결정 모델은 IGDT의 공감적 영향 개념을 기반으로 구축되었기 때문에 공감적 의사 결정 모델(SDM)이라고 명명되었습니다. SDM은 전력 시스템 및 부하 연결에 대한 RES 입력 전력을 예약하거나 다시 예약하는 데 도움이 됩니다. 먼저 제안된 모델은 불확실성 모델링 분류 및 정량화를 위해 IEEE 30 및 IEEE 123 버스 테스트 시스템에 적용되어 부하 스케줄링과 함께 RES의 침투를 지원했습니다. 제안된 SDM 모델은 위에서 언급한 목표를 달성하지 못했지만 RES 통합을 위한 IEEE 1547 전압 표준에 따라 전압 불균형을 완화하는 매우 만족스러운 방식으로 수행되었습니다. 또한, 제안된 SDM 모델은 IEEE 30 버스 테스트 시스템의 경제적인 디스패치 및 유닛 커밋을 처리하는 데에도 적용되었습니다. 성공적인 구현을 위해 제안된 SDM 모델에는 강화 학습(RL) 알고리즘이 SDM-RL 에이전트로 내장되어 있습니다. 여기서는 심층 결정론적 정책 그라데이션(DDPG) 에이전트가 RL 에이전트로 선택되었습니다. RL 에이전트는 RES 통합 전력 시스템 애플리케이션에 대한 제안된 SDM의 영향을 더욱 개선했습니다. 제안 방법론은 크게 5가지로 1) IGDT를 이용한 불확실성 분류, 2) RMV-GSA를 이용한 RES 및 부하의 영향 분석, 3) 1)과 2)의 결과를 바탕으로 ANN을 학습, 4) 의사결정 모델 형성: IGDT와 RMV-GSA에서 얻은 결과를 DNN을 통해 의사결정 세트 파라미터를 만들고, RES 및 부하의 스케줄링 또는 재스케줄링을 결정 5) UCED 사례 적용을 위해 내장된 SDM 모델 제안으로 구성됩니다. 제안한 방법론을 적용하여 전압 안정화, RES 보급, 부하조정 화력 경제급전에 큰 효과를 보였습니다.

      • Numerical Investigation of the Convective Heat Transfer Coefficient for Cross Flow Tube Banks

        ASHRAF ALI MAJED ALFANDI University of Science and Technology 2014 국내석사

        RANK : 247359

        In designing compact heat exchangers, the tube bank arrangement is of high importance since the variation of the longitudinal and transverse pitches affects the heat transfer and pressure drop in a heat exchanger. Smaller pitches allow a high performance compact heat exchanger at the expense of a high pressure drop. Normally, the transverse tube pitch is determined by a given requirement on a pressure drop limit through a heat exchanger. The longitudinal pitch has a quite different effect on the heat transfer and pressure drop depending on inline and staggered tube banks, respectively. In this study, the effect on a shell-side heat transfer coefficient is investigated using the CFD code FLUENT with variation in a longitudinal pitch to diameter ratio, SL, in the range of 1.15 to 2.6 with a fixed transverse pitch to diameter ratio. For a benchmark purpose, typical thermal-hydraulic conditions for the Zukauskas correlation are assumed. Many sensitivity calculations for different mesh sizes and turbulent models are performed to check the accuracy of the numerical solution. As a result of the turbulence sensitivity study, for the staggered tube bank case, the Realizable κ-ε turbulence model was found to be in good agreement with the results of the Zukauskas correlation among the other investigated turbulence models. On the other hand, for the inline tube bank case, the SST κ-ω turbulence model predicted the average heat transfer coefficient better than the ε-based turbulence models. The results demonstrate that as the longitudinal pitch-to-diameter ratio, SL, decreases, the overall trend of the heat transfer coefficient is different. For a staggered arrangement, the profile of the calculated heat transfer coefficient is found to be in a good agreement with the Zukauskas correlation heat transfer coefficient in the longitudinal pitch-to-diameter ratio range of 1.15 – 2.6. For the inline tube arrangement, the average heat transfer coefficient is found to be decreasing with the decrease of SL rather than being constant as predicted by Zukauskas correlation.

      • Synthesis of e trifluoromethyl- and allyl-substituted tert-alcohols by environment-friendly radical strategies

        Ashraf, Muhammad Awais 중앙대학교 대학원 2022 국내석사

        RANK : 247359

        Trifluoromethylated 분자는 의약 및 제약 화학자 사이에서 주목을 받고 있습니다. 트리플루오로메틸 및 알릴 치환된 tert-알코올을 합성하기 위해 비교적 탐구가 잘 되어있지 않은 라디칼 교차 친전자체 커플링을 이용했으며, 이를 위해 지속 가능한 광산화환원 및 전기화학적 전략을 사용했습니다. 이 반응은 까다로운 교차 라디칼-라디칼 커플링을 거치는 트리플루오로메틸 케틸 라디칼 및 알릴 라디칼 중간체를 통해 진행됩니다. 개발된 방법은 온화한 반응 조건을 가지며, 교차 커플링된 생성물을 합성하는 화학적 선택성을 가지고, 가치 있는 3차 알코올을 포함하는 트리플루오로메틸 및 알릴들을 제공합니다. 이 방법들은 또한 아마이드 생동등체로 여겨지는 트리플루오로메틸 및 알릴 그룹을 둘러싼 아민 변이체들의 합성에 사용될 수 있습니다. Trifluoromethylated molecules have gained privileged recognition among medicinal and pharmaceutical chemists. Sustainable photoredox- and electrochemical strategies were used to facilitate the comparatively less explored radical cross electrophile coupling to synthesize trifluoromethyl- and allyl-substituted tert-alcohols. Reactions proceed through trifluoromethyl ketyl radical and allyl radical intermediates which go through challenging cross radical-radical coupling. The developed transformations are benign and chemo-selective to provide cross-coupled products and deliver several valuable trifluoromethyl and allyl containing tertiary alcohols. Both procedures can also be used for the synthesis of amine variants surrounding trifluoromethyl and allyl moiety which is contemplated as amide bioisostere.

      • Design, Synthesis and Biological Evaluation of Novel Quinoline and Benzothiazole Derivatives as Potential Anticancer Agents

        ASHRAF KAREEM AWAD MOHAMMED El-DAMASY University of Science and Technology 2016 국내박사

        RANK : 247359

        Part I. Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido-pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have been designed and synthesized as anticancer sorafenib congeners. Among the synthesized derivatives, fourteen compounds were selected for evaluation of their antiproliferative activity over a panel of 60 cancer cell lines at a single dose concentration of 10 M at National Cancer Institute (NCI, USA). Four compounds, I-11b–d and I-11f showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC50 values. The data revealed that 2,4-difluorophenyl (I-11b) and 4-chloro-3-trifluoromethylphenyl (I-11d) urea compounds are the most active derivatives with significant efficacies and superior potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging particularly to renal carcinoma cell (RCC), ovarian, and non-small cell lung (NSCL) cancer. Compound I-11b and I-11d were found to be six and two times more potent than sorafenib against A498 RCC line, with IC50 values of 0.42 M and 1.36 M, respectively. Accordingly, compound I-11d was screened over a panel of 41 oncogenic kinases at single dose of 10 M to profile its kinase inhibitory activity. Interestingly, the compound showed highly selective inhibitory activities (81.8% and 96.3%) against BRAFV600E and C-RAF kinases with GI50 values of 316 nM and 61 nM, respectively. Moreover, molecular docking, cell cycle analysis, compliance to Lipinski’s rule of five, and in silico toxicity assessment have been reported. Part II. Design and synthesis of new 2-anilinoquinolines bearing N-methylpicolinamide moiety as potential antiproliferative agents A series of new 2-anilinoquinolines II-3a–o possessing the substantial N-methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogues. The antiproliferative activities of the target compounds were preliminary appraised against a panel of 3 human cancer cell lines (MCF-7, SK-BR3 and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10 M concentration. Interestingly, compounds II-3c, II-3d, II-3j, II-3k and II-3l showed promising selective anticancer activities (growth inhibition > 80%) towards certain cancer cells at 10 M testing dose. Compounds II-3d and II-3j were advanced to 5-dose testing mode to determine their GI50 values, and compared with our previously reported ureidoquinoline B (I-11d) and sorafenib as reference compounds. The 4-chloro-3-trifluoromethylaniline derivative II-3j manifested superior potency than both compound B (I-11d) and sorafenib over 11 and 8 cell lines, respectively. It showed GI50 values of 0.36 M, 0.66 M, 0.68 M and 0.60 M against the breast MDA-MB-468, renal A498 and melanoma SK-MEL-5 and UACC-62 cell lines, respectively. Moreover, both II-3d and II-3j exerted low cytotoxic effects against HFF-1 normal cell line. In addition, both II-3d and II-3j exerted low cytotoxic effects against HFF-1 normal cell line. Furthermore, compounds II-3d and II-3j were tested against both B-RafV600E and C-Raf kinases, and displayed modest inhibitory activities, which were justified by molecular docking study. Taken together, compound II-3j could serve as a promising lead compound for further development of potent anticancer chemotherapeutics. Part III. Novel 5-substituted-2-anilinoquinolines with 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety as broad spectrum antiproliferative agents: Design, Synthesis, cell based assays and kinase screening A series of new 2-anilinoquinolines possessing 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety at C5 of quinoline has been designed and synthesized as potential anticancer agents. Their antiproliferative activities were evaluated against a panel of 60 cancer cell lines at NCI and compared with gefitinib as a reference compound. Most of the tested compounds displayed potent and broad spectrum antiproliferative activities. Compounds III-5d, III-5f and III-5g showed strong inhibitory and lethal effects at 10 M concentration. Moreover, they manifested superior potencies and efficacies than gefitinib across the most tested cell lines. Compound III-5d, with 4-chloro-3-trifluoromethylphenyl group, proved to be the most potent and efficacious derivative in this series, with mean GI50 and TGI values of 1.62 M and 3.47 M, respectively. Kinase screening of III-5d against a panel of 47 oncogenic kinases revealed its selective inhibitory effect (96% inhibition) towards TrkA kinase. Furthermore, the most potent compounds showed low cytotoxic effects against HFF-1 normal cell line. Part IV. Targeting ABL-1 and ABLT315I tyrosine kinases with a new potent series of picolinamide based benzothiazoles A series of novel picolinamide based benzothiazoles (17 final compounds), targeting both wild-type and the most resistant T315I mutant of Bcr-Abl kinase, has been designed and synthesized. Moreover, a selected array (8 compounds) was evaluated for its antiproliferative activity over a panel of 60 cancer cell lines. Compound IV-6l was the most potent derivative against both native and T315I mutant ABL with IC50 values of 18.2 nM and 39.9 nM, respectively, and showed highly selective inhibitory activity (89.8%) towards the Bcr-Abl dependent leukemia cell (K-562) at 10 M concentration. Moreover, CYP450 and hERG channel inhibitory profiles compound IV-6l disclosed its low potential to possess undesirable drug–drug interactions and cardiac side effects. Significance of C6-oxypicolinamide moiety and SAR study for the C2 aliphatic side chain of benzothiazole are discussed in detail. Part V. New potent anticancer benzothiazoles featuring pyridylamide moiety and possessing dual B-RafV600E and C-Raf kinase inhibitory activities A new series of benzothiazole amide and urea derivatives tethered with the privileged pyridylamide moiety by ether linkage at the 6-position of benzothiazole (22 final compounds) has been designed and synthesized as potent anticancer sorafenib analogs. A selected group of twelve derivatives was appraised for its antiproliferative activity over a panel of 60 human cancer cell lines at a single dose concentration of 10 M at National Cancer Institute (NCI, USA). Compounds V-3b, V-4a, V-4b and V-4d exhibited promising growth inhibitions and thus were further tested in advanced 5-dose testing assay to determine their GI50 values. The cellular based assay results revealed that 3,5-bis-trifluoromethylphenyl (V-4b) urea member is the best derivative with superior potency and efficacy compared to sorafenib as well as notable extended spectrum activity covering 57 human cancer cell lines. Kinase screening of compound V-4b showed its kinase inhibitory effect against both B-RafV600E and C-Raf. Moreover, the most potent derivatives in cells were investigated for their RAF inhibitory activities, and the results were rationalized with the molecular docking study. Profiling of CYP450 and hERG channel inhibitory effects for the active compounds revealed their low possibilities to exhibit undesirable drug–drug interactions and cardiac side effects. Part VI. Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad Spectrum of Antiproliferative Activity Herein, we report the discovery of compound VI-5 (KST016366) as a new potent multikinase inhibitor through minor structural modification of our previously reported RAF kinase inhibitor A (V-4a). Preliminary anticancer evaluation of KST016366 showed a substantial antiproliferative activity against the NCI-60 cancer cell lines at 10 M. Accordingly, it was selected for the advanced 5 dose assay, and exerted a broad spectrum antiproliferative activity with single digit micromolar GI50 values. Of special significance, it showed GI50 values of 51.8 nM and 19 nM against leukemia K-562 and colon carcinoma KM12 cell lines, respectively. Kinase screening of KST016366 displayed its remarkable multiple kinase inhibitory activity in nanomolar scale over certain oncogenic kinases implicated in tumorigenesis as well as angiogenesis. Interestingly, it displayed IC50 values of 0.82 nM, 3.81 nM and 53 nM over Tie2, TrkA and ABL-1 (wild and T315I mutant) kinases, respectively. Such findings could justify its broad spectrum anticancer activity over various cancer cells. Moreover, KST016366 is orally bioavailable with a favorable PK profile. Taken together, KST016366 may serve as a promising candidate for further development of potent anticancer chemotherapeutics.

      • Energy efficient selection of re-encrypting nodes for TICK-based wireless sensor networks

        Ashraf, Muhammad Sungkyunkwan University 2019 국내석사

        RANK : 247359

        Communication cost is the most important factor in wireless sensor networks (WSNs), as sensor nodes in the network are tiny in size and are supplied with stringent energy resources. A large amount of energy is consumed in exchanging the control messages for keying or rekeying and also in the presence of a high false positive rate. A false positive rate is a ratio of dropping the healthy reports by intermediate forwarding nodes if the clock drift between two re-encrypting nodes is high. En-route filtering schemes have been proposed to handle these issues, but these schemes do not avoid the exchange of control keying messages among their nodes and thus increase the communication cost. Time-based Dynamic Keying and En-Route Filtering (TICK) and Secure Source-Based Loose Synchronization (SOBAS) have been proposed to reduce the communication cost by avoiding the exchange of control keying messages and exploit the local time values of the intermediate nodes to generate one-time dynamic keys. The generated dynamic keys are then used to encrypt the reports. Although these schemes are more energy efficient but cannot determine how to minimize the false positive rate, a valid message might be dropped because the clock drift between the two nodes is too large, and therefore the key falls outside of the time window of the forwarder. As the number of hops between the source and forwarding node increases, the clock drift is more unbounded, therefore the probability of a false positive increase. SOBAS address the false positive rate to some extent by employing selective re-encrypting nodes strategy in which fixed nodes are selected to encrypt the reports. But the selection of re-encrypting nodes is not efficient and dynamic network conditions (i.e., the residual energy of en-route nodes, hop count, and false positive rate) are also not focused in SOBAS. This dissertation presents energy efficient selection of re-encrypting nodes based on fuzzy logic in TICK-based wireless sensor networks. Fuzzy rule-based selection of re-encrypting nodes helps to improve the proximity and maintain the clock drift between two re-encrypting nodes. The proposed scheme potentially reduces the energy consumption of the forwarding nodes by considering the remaining energy level (REL) of the forwarding nodes, the hop counts (HC) between two consecutive re-encryption nodes, and the false positive ratio (FPR). In the presence of high FPR, the transmission energy can be saved by choosing encryption nodes closer to one another to filter false report earlier. In the absence of or low FPR, the computational energy can be saved by choosing lesser and relatively farther encryption nodes from one another. Genetic algorithm (GA)-based optimization technique is used to optimize the fuzzy membership functions, as membership functions optimization is equally important to improve the selection of re-encrypting nodes which further helps to reduce the communication cost and false positive rate in the network. The proposed method automatically optimizes the fuzzy membership functions with minimal human intervention and expertise and save much time in the optimization process.

      • Synergic effects of ammonia on secondary organic aerosol formation in laboratory and field measurements : 실험실 및 현장 측정에서 이차 유기 에어로졸 생성에 대한 암모니아의 상승 효과

        Ashraf, Fawad 경북대학교 대학원 2022 국내박사

        RANK : 247359

        Secondary organic aerosol (SOA) formation from the photo-oxidation of anthropogenic and biogenic volatile organic compounds (VOCs) were investigated in an indoor smog chamber at a relative humidity of about 60% in NOx/SO2/NH3 mixture, with HONO as a precursor of OH radical, and (NH4)2SO4 seed particles. A significant increase in SOA yield was observed in the presence of NH3 compared to that in the absence of NH3. SOA formed in the presence of NH3 showed higher fractions of oxidized organic functional group of carbonyl. SOA formation yields were well correlated with aerosol water content, indicating the possibility of heterogeneous SOA formation. An oxidation flow reactor was deployed to measure secondary aerosol formation potential of PM2.5 in NH3−rich conditions of agricultural areas. The chemical composition of ambient PM2.5 was dominated in the order of NO3- > OM > NH4+ > SO42-. A prominent effect of NH3 on the enhancement of secondary aerosol formation was observed when ambient air was aged at the condition of high NOx and high RH. Source apportionment of organic aerosol by positive matrix factorization (PMF) resulted in 4 factors in the order of oxidized organic aerosol >> cooking organic aerosol > hydrocarbon-like organic aerosol > biomass burning organic aerosol. Aerosol water content showed a positive correlation with oxidized organic aerosol apportioned by PMF, with substantial increase in the correlation at nighttime. Thermal gravimetric analysis/differential scanning calorimetry was used to estimate the molar heat capacity, melting point and enthalpy, and vaporization enthalpy (∆Hv) of SOA components. Heat capacity of benzoic acid, phthalic acid, ketopinic acid, cis-pinonic acid, and diaterpenylic acid acetate (DTAA) was 118.1, 169.4, 223.9, 246.1, and 524.1 J mol−1 K−1, respectively. The ∆Hv of benzoic acid, phthalic acid, ketopinic acid, DTAA, and 3-methylbutane-1,2,3-tricarboxylic acid was 93.2 ± 0.4, 131.6, 113.8, and 124.4 kJ mol−1, respectively. The melting enthalpies of the SOA components range from 7.3 to 29.7 kJ mol−1. A thermodenuder was used to measure the volatility properties of α-pinene SOA formed by a flow reactor. Using the single product model of integrated volume method (IVM) for α-pinene SOA at 25 oC, saturation vapor pressures were determined as 3.4.  10-4, 1.1  10-3, 8.0  10-3, 8.9  10-3 Pa, and ∆Hv values were 98.75, 74.83, 12.61, 20.31 kJ mol-1 at atmospheric chemistry equivalent OH exposure of 0.5, 2.0, 3.0 and 5.0 d, respectively. Two-product model using IVM method was examined to obtain the volatility data for low volatile and high volatile SOA products. 실내 스모그 챔버에서 인위적 및 생물 기원 휘발성 유기 화합물의 광산화 반응에 의한 이차 유기 에어로졸(secondary organic aerosol : SOA) 생성을 NOx/SO2/NH3 혼합가스에서 OH 라디칼의 전구체로 HONO, 핵 입자로 (NH4)2SO4를 사용하여 약 60% 상대습도에서 연구하였다. SOA 수율은 NH3가 있는 경우에 없는 경우에 비해 유의하게 증가하였다. NH3가 있는 조건에서 생성된 SOA는 산화된 작용기인 카보닐의 분율이 더 높게 나왔다. SOA 생성 수율은 에어로졸 물 함량과 좋은 상관 관계가 있었으며, 이것은 비균질상 SOA 생성의 가능성을 나타낸다. NH3가 풍부한 조건인 농촌지역에서 산화 흐름 반응기를 사용하여 PM2.5의 이차 에어로졸 생성 잠재력을 측정하였다. 대기 PM2.5의 화학 조성은 NO3- > OM > NH4+ > SO42- 순서로 나타났다. 고 NOx 및 고습도 조건에서 대기가 노화 반응했을 때 이차 에어로졸 생성의 증가에 대한 NH3의 효과가 두드러졌다. Positive matrix factorization (PMF)에 의한 유기 에어로졸의 오염원 산정에서 4개 오염원이 산화 유기에어로졸 >> 요리 유기에어로졸 > 유사 탄화수소 유기에어로졸 > 생체소각 유기에어로졸 순서로 확인되었다. 에어로졸 물 함량은 PMF로 산정된 산화 유기에어로졸과 양의 상관관계를 보였고, 야간에 더 높은 상관성을 보였다. 열중량분석/시차주사열량법을 이용하여 SOA 화학성분의 몰 열용량, 용해 온도 및 엔탈피, 기화 엔탈피(∆Hv)를 추정하였다. Benzoic acid, phthalic acid, ketopinic acid, cis-pinonic acid, and diaterpenylic acid acetate (DTAA)의 열용량은 각각 118.1, 169.4, 223.9, 246.1 및 524.1 J mol-1 K-1이었다. benzoic acid, phthalic acid, ketopinic acid, DTAA, and 3-methylbutane-1,2,3-tricarboxylic acid의 ∆Hv는 각각 93.2 ± 0.4, 131.6, 113.8 및 124.4 kJ mol-1이었다. SOA 성분들의 용해 엔탈피는 7.3 ~ 29.7 kJ mol-1 이었다. 열 디누더를 이용하여 흐름 반응기에서 생성된 α-피넨 SOA의 휘발 특성을 측정하였다. Integrated Volume Method (IVM)의 단일 생성물 모델을 사용하여 0.5, 2.0, 3.0, 5.0 d 대기화학 등가 OH 노출 조건에서 생성된 α-피넨 SOA의 25 ˚C에서 포화 증기압은 3.4  10-4, 1.1  10-3, 8.0  10-3, 8.9  10-3 Pa, ∆Hv 값은 각각 98.75, 74.83, 12.61, 20.31 kJ mol-1로 각각 결정되었다. IVM법에 기반한 2 생성물 모델을 사용하여 저휘발성 및 고휘발성 SOA 성분의 휘발 데이터를 구하는 시도를 하였다.

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