Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging
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- Journal of Radiopharmaceuticals and Molecular Probes
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- v.9 no.1
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- pp.9-16
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- 2023
Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.
The studies are to know how much cocoon crops is damaged by the stained leaf with nicotine produced from the tobacco field cultivated in mulching system in spring season and by residual nicotine in autumn season. Furthermore, the new knowledges are to make both industries keep up with their development. In spring season mulberry Held is located higher on the West-North of tobacco held below 20 degrees of slope and with 36 per cent of East-South wind and 18 per cent of South wind blowing from tobacco fold to the mulberry fold. In addition, silkworm larvae are fed with the mulberry leaf produced in the different plots placing by the different distances, l0m, 25m, 50m, 80m, and loom far from the tobacco Held as a control and it is also considered that narcotic larvae including the dead larvae are not observed. On the other hand, it is noted that better leaf quality and abundant growth of mulberry tree is produced from the mulberry fold closer to the tobacco field and with a low slope. 1) Maximum weight of larval body at the 5th stage is damaged by the stained leaf with the nicotine up to 25m far from the tobacco held. 2) The larvae fed with the mulberry leaf in mulberry Held up to 25m far from the tobacco fold produce small number of the fresh cocoons per 1 liter. 3) Low single cocoon weight and low cocoon shell weight are produced by the poison damaged larvae fed with the mulberry. leaf up to 25m far from the tobacco field and weight of cocoon shell is damaged higher than the single cocoon weight. It is resulted in low percentage of cocoon shell. 4) Cocoon yield including the double cocoon from 10,000 larvae is decreased by the larvae fed with the stained leaf in the mulberry fold up to 25m far from the tobacco fold and 19 per cent of cocoon yield is decreased with 2.4kg of cocoon yield in l0m plot and with 2.5kg of cocoon yield in 25m plot at the first season and at the 2nd season with 1.8kg o( cocoon yield in l0m plot and with 11.5kg of cocoon yield in 25m plot, 11 per cent and 9 per cent of cocoon yield including double cocoon from 10,000 larvae is decreased, as compared with the control, respectively. With these results, it is observed that nicotine damage is occurred to the silkworm larvae if the larvae are fed with the leaf in the mulberry Held within 25m-50m far from the tobacco field.
Artificial intelligence (AI) is one of the main driving forces leading the Fourth Industrial Revolution. The technologies associated with AI have already shown superior abilities that are equal to or better than people in many fields including image and speech recognition. Particularly, many efforts have been actively given to identify the current technology trends and analyze development directions of it, because AI technologies can be utilized in a wide range of fields including medical, financial, manufacturing, service, and education fields. Major platforms that can develop complex AI algorithms for learning, reasoning, and recognition have been open to the public as open source projects. As a result, technologies and services that utilize them have increased rapidly. It has been confirmed as one of the major reasons for the fast development of AI technologies. Additionally, the spread of the technology is greatly in debt to open source software, developed by major global companies, supporting natural language recognition, speech recognition, and image recognition. Therefore, this study aimed to identify the practical trend of AI technology development by analyzing OSS projects associated with AI, which have been developed by the online collaboration of many parties. This study searched and collected a list of major projects related to AI, which were generated from 2000 to July 2018 on Github. This study confirmed the development trends of major technologies in detail by applying text mining technique targeting topic information, which indicates the characteristics of the collected projects and technical fields. The results of the analysis showed that the number of software development projects by year was less than 100 projects per year until 2013. However, it increased to 229 projects in 2014 and 597 projects in 2015. Particularly, the number of open source projects related to AI increased rapidly in 2016 (2,559 OSS projects). It was confirmed that the number of projects initiated in 2017 was 14,213, which is almost four-folds of the number of total projects generated from 2009 to 2016 (3,555 projects). The number of projects initiated from Jan to Jul 2018 was 8,737. The development trend of AI-related technologies was evaluated by dividing the study period into three phases. The appearance frequency of topics indicate the technology trends of AI-related OSS projects. The results showed that the natural language processing technology has continued to be at the top in all years. It implied that OSS had been developed continuously. Until 2015, Python, C ++, and Java, programming languages, were listed as the top ten frequently appeared topics. However, after 2016, programming languages other than Python disappeared from the top ten topics. Instead of them, platforms supporting the development of AI algorithms, such as TensorFlow and Keras, are showing high appearance frequency. Additionally, reinforcement learning algorithms and convolutional neural networks, which have been used in various fields, were frequently appeared topics. The results of topic network analysis showed that the most important topics of degree centrality were similar to those of appearance frequency. The main difference was that visualization and medical imaging topics were found at the top of the list, although they were not in the top of the list from 2009 to 2012. The results indicated that OSS was developed in the medical field in order to utilize the AI technology. Moreover, although the computer vision was in the top 10 of the appearance frequency list from 2013 to 2015, they were not in the top 10 of the degree centrality. The topics at the top of the degree centrality list were similar to those at the top of the appearance frequency list. It was found that the ranks of the composite neural network and reinforcement learning were changed slightly. The trend of technology development was examined using the appearance frequency of topics and degree centrality. The results showed that machine learning revealed the highest frequency and the highest degree centrality in all years. Moreover, it is noteworthy that, although the deep learning topic showed a low frequency and a low degree centrality between 2009 and 2012, their ranks abruptly increased between 2013 and 2015. It was confirmed that in recent years both technologies had high appearance frequency and degree centrality. TensorFlow first appeared during the phase of 2013-2015, and the appearance frequency and degree centrality of it soared between 2016 and 2018 to be at the top of the lists after deep learning, python. Computer vision and reinforcement learning did not show an abrupt increase or decrease, and they had relatively low appearance frequency and degree centrality compared with the above-mentioned topics. Based on these analysis results, it is possible to identify the fields in which AI technologies are actively developed. The results of this study can be used as a baseline dataset for more empirical analysis on future technology trends that can be converged.
At the initial stage of Internet advertising, banner advertising came into fashion. As the Internet developed into a central part of daily lives and the competition in the on-line advertising market was getting fierce, there was not enough space for banner advertising, which rushed to portal sites only. All these factors was responsible for an upsurge in advertising prices. Consequently, the high-cost and low-efficiency problems with banner advertising were raised, which led to an emergence of keyword advertising as a new type of Internet advertising to replace its predecessor. In the beginning of 2000s, when Internet advertising came to be activated, display advertisement including banner advertising dominated the Net. However, display advertising showed signs of gradual decline, and registered minus growth in the year 2009, whereas keyword advertising showed rapid growth and started to outdo display advertising as of the year 2005. Keyword advertising refers to the advertising technique that exposes relevant advertisements on the top of research sites when one searches for a keyword. Instead of exposing advertisements to unspecified individuals like banner advertising, keyword advertising, or targeted advertising technique, shows advertisements only when customers search for a desired keyword so that only highly prospective customers are given a chance to see them. In this context, it is also referred to as search advertising. It is regarded as more aggressive advertising with a high hit rate than previous advertising in that, instead of the seller discovering customers and running an advertisement for them like TV, radios or banner advertising, it exposes advertisements to visiting customers. Keyword advertising makes it possible for a company to seek publicity on line simply by making use of a single word and to achieve a maximum of efficiency at a minimum cost. The strong point of keyword advertising is that customers are allowed to directly contact the products in question through its more efficient advertising when compared to the advertisements of mass media such as TV and radio, etc. The weak point of keyword advertising is that a company should have its advertisement registered on each and every portal site and finds it hard to exercise substantial supervision over its advertisement, there being a possibility of its advertising expenses exceeding its profits. Keyword advertising severs as the most appropriate methods of advertising for the sales and publicity of small and medium enterprises which are in need of a maximum of advertising effect at a low advertising cost. At present, keyword advertising is divided into CPC advertising and CPM advertising. The former is known as the most efficient technique, which is also referred to as advertising based on the meter rate system; A company is supposed to pay for the number of clicks on a searched keyword which users have searched. This is representatively adopted by Overture, Google's Adwords, Naver's Clickchoice, and Daum's Clicks, etc. CPM advertising is dependent upon the flat rate payment system, making a company pay for its advertisement on the basis of the number of exposure, not on the basis of the number of clicks. This method fixes a price for advertisement on the basis of 1,000-time exposure, and is mainly adopted by Naver's Timechoice, Daum's Speciallink, and Nate's Speedup, etc, At present, the CPC method is most frequently adopted. The weak point of the CPC method is that advertising cost can rise through constant clicks from the same IP. If a company makes good use of strategies for maximizing the strong points of keyword advertising and complementing its weak points, it is highly likely to turn its visitors into prospective customers. Accordingly, an advertiser should make an analysis of customers' behavior and approach them in a variety of ways, trying hard to find out what they want. With this in mind, her or she has to put multiple keywords into use when running for ads. When he or she first runs an ad, he or she should first give priority to which keyword to select. The advertiser should consider how many individuals using a search engine will click the keyword in question and how much money he or she has to pay for the advertisement. As the popular keywords that the users of search engines are frequently using are expensive in terms of a unit cost per click, the advertisers without much money for advertising at the initial phrase should pay attention to detailed keywords suitable to their budget. Detailed keywords are also referred to as peripheral keywords or extension keywords, which can be called a combination of major keywords. Most keywords are in the form of texts. The biggest strong point of text-based advertising is that it looks like search results, causing little antipathy to it. But it fails to attract much attention because of the fact that most keyword advertising is in the form of texts. Image-embedded advertising is easy to notice due to images, but it is exposed on the lower part of a web page and regarded as an advertisement, which leads to a low click through rate. However, its strong point is that its prices are lower than those of text-based advertising. If a company owns a logo or a product that is easy enough for people to recognize, the company is well advised to make good use of image-embedded advertising so as to attract Internet users' attention. Advertisers should make an analysis of their logos and examine customers' responses based on the events of sites in question and the composition of products as a vehicle for monitoring their behavior in detail. Besides, keyword advertising allows them to analyze the advertising effects of exposed keywords through the analysis of logos. The logo analysis refers to a close analysis of the current situation of a site by making an analysis of information about visitors on the basis of the analysis of the number of visitors and page view, and that of cookie values. It is in the log files generated through each Web server that a user's IP, used pages, the time when he or she uses it, and cookie values are stored. The log files contain a huge amount of data. As it is almost impossible to make a direct analysis of these log files, one is supposed to make an analysis of them by using solutions for a log analysis. The generic information that can be extracted from tools for each logo analysis includes the number of viewing the total pages, the number of average page view per day, the number of basic page view, the number of page view per visit, the total number of hits, the number of average hits per day, the number of hits per visit, the number of visits, the number of average visits per day, the net number of visitors, average visitors per day, one-time visitors, visitors who have come more than twice, and average using hours, etc. These sites are deemed to be useful for utilizing data for the analysis of the situation and current status of rival companies as well as benchmarking. As keyword advertising exposes advertisements exclusively on search-result pages, competition among advertisers attempting to preoccupy popular keywords is very fierce. Some portal sites keep on giving priority to the existing advertisers, whereas others provide chances to purchase keywords in question to all the advertisers after the advertising contract is over. If an advertiser tries to rely on keywords sensitive to seasons and timeliness in case of sites providing priority to the established advertisers, he or she may as well make a purchase of a vacant place for advertising lest he or she should miss appropriate timing for advertising. However, Naver doesn't provide priority to the existing advertisers as far as all the keyword advertisements are concerned. In this case, one can preoccupy keywords if he or she enters into a contract after confirming the contract period for advertising. This study is designed to take a look at marketing for keyword advertising and to present effective strategies for keyword advertising marketing. At present, the Korean CPC advertising market is virtually monopolized by Overture. Its strong points are that Overture is based on the CPC charging model and that advertisements are registered on the top of the most representative portal sites in Korea. These advantages serve as the most appropriate medium for small and medium enterprises to use. However, the CPC method of Overture has its weak points, too. That is, the CPC method is not the only perfect advertising model among the search advertisements in the on-line market. So it is absolutely necessary that small and medium enterprises including independent shopping malls should complement the weaknesses of the CPC method and make good use of strategies for maximizing its strengths so as to increase their sales and to create a point of contact with customers.
According to Soil Taxonomy which has been developed over the past 20 years in the soil conservation service of the U. S. D. A, Soils in Korea are classified. This system is well suited for the classification of the most of soils. But paddy field soils have some difficulties in classification because Soil Taxonomy states no proposals have yet been developed for classifying artificially irrigated soils. This paper discusses some problems in the application of Taxonomy and suggestes the classification of paddy field soils in Korea. Following is the summary of the paper. 1. Anthro aquic, Aquic Udipsamments : The top soils of these soils are saturated with irrigated water at some time of year and have mottles of low chroma(2 or less) more than 50cm of the soil surface. (Ex. Sadu, Geumcheon series) 2. Anthroaquic Udipsamments : These sails are like Anthroaquic, Aquic Udipsamments except for the mottles of low chroma within 50cm of the soil surface. (Ex. Baegsu series) 3. Halic Psammaquents : These soils contain enough salts as distributed in the profile that they interfere with the growth of most crop plants and located on the coastal dunes. The water table fluctuates with the tides. (Ex. Nagcheon series) 4. Anthroaquic, Aquic Udifluvents : They have some mottles that have chroma of 2 or less in more than 50cm of the surface. The upper horizon is saturated with irrigated water at sometime. (Ex. Maryeong series) 5. Anthro aquic Udifluvents : These soils are saturated with irrigated water at some time of year and have mottles of low chroma(2 or less) within 50cm of the surface soils. (Ex. Haenggog series) 6. Fluventic Haplaquepts : These soils have a content of organic carbon that decreases irregularly with depth and do not have an argillic horizon in any part of the pedon. Since ground water occur on the surface or near the surface, they are dominantly gray soils in a thick mineral regolith. (Ex Baeggu, Hagseong series) 7. Fluventic Thapto-Histic Haplaquepts : These soils have a buried organic matter layer and the upper boundary is within 1m of the surface. Other properties are same as Fluventic Haplaquepts. (Ex. Gongdeog, Seotan series) 8. Fluventic Aeric Haplaquepts : These soils have a horizon that has chroma too high for Fluventic Haplaquepts. The higher chroma is thought to indicate either a shorter period of saturation of the whole soils with water or some what deeper ground water than in the Fluventic Haplaquepts. The correlation of color with soil drainage classes is imperfect. (Ex. Mangyeong, Jeonbug series) 9. Fluventic Thapto-Histic Aeric Haplaquepts : These soils are similar to Fluventic Thapto Histic Haplaquepts except for the deeper ground water. (Ex. Bongnam series) 10. Fluventic Aeric Sulfic Haplaquepts : These soils are similar to Fluventic Aeric Haplaquepts except for the yellow mottles and low pH (<4.0) in some part between 50 and 150cm of the surface. (Ex. Deunggu series) 11. Fluventic Sulfaquepts : These soils are extremely acid and toxic to most plant. Their horizons are mostly dark gray and have yellow mottles of iron sulfate with in 50cm of the soil surface. They occur mainly in coastal marshes near the mouth of rivers. (Ex. Bongrim, Haecheog series) 12. Fluventic Aeric Sulfaquepts : They have a horizon that has chroma too high for Fluventic Sulfaquepts. Other properties are same as Fluventic Sulfaquepts. (Ex. Gimhae series) 13. Anthroaquic Fluvaquentic Eutrochrepts : These soils have mottles of low chroma in more than 50cm of the surface due to irrigated water. The base saturation is 60 percent or more in some subhroizon that is between depth of 25 and 75cm below the surface. (Ex. Jangyu, Chilgog series) 14. Anthroaquic Dystric Fluventic Eutrochrepts : These soils are similar to Anthroaquic Fluvaquentic Eutrochrepts except for the low chroma within 50cm of the surface. (Ex. Weolgog, Gyeongsan series) 15. Anthroaquic Fluventic Dystrochrepts : These soils have mottles that have chroma of 2 or less within 50cm of the soil surface due to artificial irrigation. They have lower base saturation (<60 percert) in all subhorizons between depths of 25 and 75cm below the soil surface. (Ex. Gocheon, Bigog series) 16. Anthro aquic Eutrandepts : These soils are similar to Anthroaquic Dystric Fluventic Eutrochrepts except for lower bulk density in the horizon. (Ex. Daejeong series) 17. Anthroaquic Hapludalfs : These soils' have a surface that is saturated with irrigated water at some time and have chroma of 2 or less in the matrix and higher chroma of mottles within 50cm of the surface. (Ex. Hwadong, Yongsu series) 18. Anthro aquic, Aquic Hapludalfs : These soils are similar to Anthro aquic Hapludalfs except for the matrix that has chroma 2 or less and higher chroma of mottles in more than 50cm of the surface. (Ex. Geugrag, Deogpyeong se ries)