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Genenation of structural diversity in polyketides by combinatorial biosynthesis of polyketides: Part I. Generation of multiple bioactive macrolides by hybrid modular polyketide synthases in Streptomyces venezuelae, Part II. Production of novel rifamycins by combinatorial biosynthesis

  • Yoon, Yeo-Joon
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2002.10a
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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.

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The History of the History of Religions and Intellectual History : Concerning with the Work of Hans G. Kippenberg (서구 종교학의 역사에 대한 지성사적 재조명: 키펜베르크의 논의를 중심으로)

  • Jo, Hyeon-Beom
    • Journal of the Daesoon Academy of Sciences
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    • v.17
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    • pp.113-134
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    • 2004
  • According to Hans Kippenberg, the foundation of an academic study of religions coincided with the beginnings of modernization. Since the second half of the nineteenth century most European countries were involved in a process of rapid social change. The repercussions that this had for daily life were momentous. Instead of working for their traditional needs, people now had to produce goods for a market. Old customs ceded to private contracts and political laws. The superior knowledge of science replaced the inherited worldview. This deep changed severed societies from their ties to the past. Many educated people in Europe believed in an imminent end of all religions. Had not the scientific progress superseded the religious worldview? Historians had to come to terms with that expectation when they directed their attention to historical religions. Friedrich Max Muller introduced a new science, so-called Religionswissenschaft through the study of the ancient Vedic sources. He thought that genuine religion was a taste for, and sense of, the infinite. From his point of view, the Indian sources confirm that nature is more than mechanical laws. Thus his interpretation sought to contradict the materialist ideology of his day. Edward Burnett Tylor described religions as a kind of natural philosophy. His notion of 'soul' functioned to explain natural events. This legacy of the past cannot be missed even in modern society. Only the concept of the soul may preserve human dignity in an age of materialism. Gerardus van der Leeuw, also tried to perform the same function of the cultural critique for the renewal of the religious imagination in modern, rationalized Europe imprisoned in the iron-cage. In this respect, we could think that the interpretations of the history of the History of Religions in the light of the intellectual history are very suggestive for the korean student of religion. It helps them to describe the early history of the study of religion in Korea. For example, Yi Neung Wha(李能和) is regarded as 'a father of korean religious studies, but no one could present a proper answer for the question of why and through which connection of his intellectual milieu he was interested in the religious history and the study of religion. We would discover its signification in his confrontation of the prevailing social thought, such as social evolutionism.

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A Study on the Job Transfer of Dental Technicians (치과기공사의 이직에 관한 연구)

  • Kwon, Eun-Ja;Bae, Sang-Mok
    • Journal of Technologic Dentistry
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    • v.25 no.1
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    • pp.173-185
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    • 2003
  • This study mainly intends to determine the factors for which dental technicians are satisfied with their jobs and how much the resulting job transfer rate is and thus to identify the correlation between them. For these purpose, 200 subjects were sampled out of dental technicians in Seoul and Incheon, and the survey was performed from July 19, 2002 to August 15 (for 25 days) with self-administered questionnaire. Out of all collected questionnaires, 131 pieces(65.5%) were addressed for this study. As for the tools for this study, the structured questionnaire was used with its proven reliability and feasibility, and the contents of questionnaire consisted of 32 questions on the basis of related references. The contents of questionnaire were categorized into 3 sections: General attribute of subjects; Factors for which dental technicians are satisfied with their jobs; and their intention of job transfer. The questionnaire consisted of total 32 questions which included general attribute of subjects(10 questions), factors of their satisfaction with jobs(17 questions) and intention of job transfer(5 questions). The data analysis was processed by computerized system with SPSS(Statistical Package for Social Sciences). Statistical analysis techniques included frequency, percentage, T-test, F-test analysis and regression analysis. As a result of those analyses, the conclusion can be summarized as follows: 1. As a result of analyzing the factors for which the subjects were satisfied with their jobs, it was found that there were significant differences in career and job title out of question items(P<0.001). It was also shown that the factors of subjects' satisfaction averaged 3.43, which was considerably higher value than I expected. It was found that job and management factors were major job satisfaction factors. 2. As a result of analyzing the intention of subjects to decide their job transfer, it was found that there were significant differences in job title and marital status out of question items(P<0.001). It was shown that the total average of the intention of their job transfer amounted to 3.06. It was shown that dental technicians have relatively higher intention of job transfer from their current work place. 3. It was found that there was inverse correlation between the factors of subjects' satisfaction with their jobs and their intention of job transfer(r=-0.490, P<0.05). Likewise, it was also found that there was inverse correlation mostly between the evaluation value for each independent variable region in term of each factor of job satisfaction and the value for the intention of job transfer. In view of these correlations, it was concluded that higher job satisfaction likely led to lower job transfer. 4. As a result of regression analysis so as to determine the influences of job satisfaction factors on the intention of job transfer, it was found that the highest influential factor was management factor. And it was shown that the test values of model were statistically significant and its explanatory power amounted to 54.6%.

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Attitudinal Study of Korean Oriental Medical Doctors toward the Educational Necessity of Human Social Medical Study in the Curriculum of Korean Oriental Medicine (한의학 교육과정의 인문사회의학 교육필요성에 대한 한의사의 태도 연구)

  • Lee, Hyun-Ji;Hong, Jin-Woo;Hong, Seung-Pyo;Lim, Young-Kyu;Kim, Dong-Ki;Jung, Jae-Geol;Lee, Sung-Yeon;Kwon, Young-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.1134-1141
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    • 2010
  • The standardized education for medical college students not only provides the opportunity to get the exclusive knowledge as a professional but also is the basis of strong professional authority. Korean Oriental medicine has pursued to standardize the education system and curricula away from the traditional education system since the modernization started. And this standardization has worked as the basis of the status advancement of Korean Oriental medicine. Through the standardization of education system and curricula, Korean Oriental medicine has been professionalized and its social status has been heightened, stabilizing itself within the establishment of institution. After this, Korean Oriental medicine has kept pursuing standardization and professionalization in the educational area. It has achieved the professionalization of curricula reflecting the specificity of Korean Oriental medicine, following the model of western medical education. This paper investigated the attitude of Korean Oriental medical doctors toward the current Korean Oriental medical education. In the survey conducted in this study, how the Korean Oriental doctors view the education of Korean Oriental college in the areas such as 'standardization', 'specificity', 'Korean Oriental medical philosophy', 'responsibility', and 'professional ethics'. And the relationship between the demographic variables of Korean Oriental medical doctors and the educational contents which should be emphasized in Korean Oriental medical school has been examined. The subjects of this study were Korean Oriental medical doctors who work as professionals after graduation of Koran Oriental Medical School and, thus, this is a meaningful study in that the contents of education which the Korean Oriental medical doctors think are needed in practice are discussed.

A Study on Pauperization Process of Low-Income Woman Head of Household (저소득 여성가구주의 빈곤화 과정에 대한 연구)

  • Chung, Mi-Suk
    • Korean Journal of Social Welfare
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    • v.59 no.4
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    • pp.191-216
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    • 2007
  • This study focuses on the problem of feminization of poverty that is formed within family relations. In order to approach this question, this study analyses the process of becoming poor through the life stories of ten woman are now heads of a household. There are differences among the study participants in the process of becoming a member of a low-income class. I have classified them into two groups depending on the routes they are led into the low-income class; one is the continuation of poverty group, and the other is the new members of the low-income class group. The continuation of poverty group is the case where they have been poor since their childhood and are still poor in their adulthood. The new members of the low-income class group is the case where you have become a low-income class sometime around divorce. The difference of the groups are related to the differences of the ways the power relationships work within a family. Women head of a household are prone to poverty because of the discrimination in formation, distribution and control of resources in their original family and their family formed by marriage. The norm of male breadwinner worked as a discrimination device. But this kind of discrimination device showed differences in their workings according to class. The continuation of poverty group experienced exclusion in the gendered responsibility of supporting the family and maintaining the family, whereas the other group experienced exclusion through the gendered nature of the distribution and control of resources. By showing that the presupposition of discussions on the poverty of woman head of a household is false, these findings challenge the existing view that as long as 'The Family' is maintained women will not be poor.

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Inhalation of Bacterial Cellulose Nanofibrils Triggers an Inflammatory Response and Changes Lung Tissue Morphology of Mice

  • Silva-Carvalho, Ricardo;Silva, Joao P.;Ferreirinha, Pedro;Leitao, Alexandre F.;Andrade, Fabia K.;da Costa, Rui M. Gil;Cristelo, Cecilia;Rosa, Morsyleide F.;Vilanova, Manuel;Gama, F. Miguel
    • Toxicological Research
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    • v.35 no.1
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    • pp.45-63
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    • 2019
  • In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

Sanitary Officials' Affairs State and Attitude about Transfer of Sanitary Affairs Control to Health Center (위생담당 공무원의 직무실태와 위생업무의 보건소 이관에 대한 태도)

  • Son, Sung-Ho;Kam, Sin;Park, Jae-Yong;Park, Ki-Soo;Han, Chang-Hyun;Cha, Byung-Jun
    • Health Policy and Management
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    • v.9 no.3
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    • pp.129-148
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    • 1999
  • This study was performed to investigate contents of affairs and job satisfaction of sanitary officials at sanitary department and health center. and to assess attitude about transfer of sanitary affairs control to health center and to devise Improving program of sanitary affairs. Four-hundred and fifty-five sanitary officials were sent a postal questionnaire and eighty-four percent completed and returned the questionnaire (382 persons). The major results are as follows: The major sanitary affairs performed by sanitary officials were permission and filing of restaurant business (15.1%), supervision and regulation of that (14.4%). Sanitary officials answered that supervision and regulation of insanitary and/or subquality foods, planning of food sanitary administration, and permission and filing of restaurant business were their important affairs. They replied that the most serious problem of sanitary affairs was 'lack of contribution to the public health' (40.9%), 'putting first in supervision' (26.4%), and 'lack of personnels' ( 19.1 %), and the most important thing to improve sanitary affairs was the substantial inherent affairs. And they indicated that the agency to be desired for sanitary affairs control was the sanitary department (51.6%), the health center (25.4%), For the degree of satisfaction in affairs, 29.1% of sanitary officials felt proud, 59.6% felt overwork, 59.3% hoped transferring to other worksite and the major reason of transferring was lack of promotion opportunity in officials of sanitary department. disciplinary punishment and social corrupt view in officials at health center. The 41.1 % of sanitary officials at sanitary department didn't know that sanitary affairs had been stated as affairs of the health center in Community Health Act. After transferring affairs control to the health center, 14.4% of them felt more proud of affairs but 20.0% less proud. 23.2% more satisfactory but 22.4% more dissatisfactory. and 64.8% answered that sanitary affairs did not change. The results indicate that sanitary affairs should be changed to supervise and control insanitary and/or subquality foods, so that they play an important role at health promotion, and make sanitary officials feel proud at their own work.

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The Effect of Knowledge Complementarity and PMO Implementation System on Performance of IT Project (지식 상호보완성과 PMO수행체계가 IT 프로젝트 성과에 미치는 영향)

  • Kim, Choong-Nyoung;Jang, Ji-Yeon;Choi, Kyu-Jin
    • Management & Information Systems Review
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    • v.37 no.4
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    • pp.141-156
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    • 2018
  • PMO(Project Management Office) has been considered as a general approach for the successful operation of IT project. The previous studies tended to emphasize on the roles and functions of PMO in a normative way. However, in practice, since PMO is operated as a joint structure in which client firms and professional PMOs work together, it seems to be important that the implementation system of PMO should be properly formed. In this paper, it is examined whether the competence of client firms and professional PMO influence on the setup of implementation system of PMO, and also whether implementation system of PMO influence of the performance of IT project. In addition, it is also analyzed if the competence of client firms and professional PMO influence differently on the setup of implementation system of PMO, according to the degree of knowledge complementarity. As a result of this study, it is found that the competence of client firms and professional PMO influence positively on the setup of implementation system of PMO, and governance factors such as clear definition of organizational roles, responsibility, and setup of standardized processes are also important in performance of IT project. It is also shown that, if knowledge complementarity is formed with a common knowledge base between client firms and professional PMOs, Project Management Office functions effectively. In summary, for the successful performance of IT project, it seems that it is required to approach from the view point of governance in forming the implementation system of PMO and it is also important to form knowledge complementarity between client firms and professional PMOs.

The Knowledge Transfer of Tesco UK into Korea, in Terms of Retailer Brand Development and Handling Processes

  • Cho, Young-Sang
    • Journal of Distribution Science
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    • v.9 no.2
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    • pp.13-24
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    • 2011
  • With the increasing market share of retailer brands, many authors have paid considerable attention to retailer brands. Before market liberalisation in 1996 in Korea, retailer brand market was led by the supermarket retailing format, although the first retailer brand product was developed by the department store format. In parallel with the entry of foreign multiple retailers, the retailer brand market has experienced rapid growth. Particularly, the expansion of Tesco UK with well-established retailing know-how into Korea has encouraged Tesco Korea to actively get involved in retailer brand program. As a result, Tesco Korea has led retailer brand market in the Korean marketplace. The research starts with the question of why Tesco Korea has achieved such a higher retailer brand share. Accordingly, this study is to explore how Tesco UK has transferred its own retailing knowledge into Tesco Korea, in terms of retailer brand program development. In order to explore why the retailer brand share of Tesco Korea is higher than that of its counterparts, the author adopted in-depth interview with prepared-questions and store observation as a research methodology. To examine working process as well as information flows within Tesco Korea and from UK to Korea, in-depth interview method is one of the most suitable research methodologies, because of the difficulty of quantifying information or data related to work flows. In addition, to increase the validity of information, the researcher had interviews with Tesco Korea supplier and store personnel. Based on these research techniques, this research explored how Tesco UK has influenced or advised Tesco Korea, particularly, from the point of view of knowledge transfer. Since the entry of Tesco UK into Korea as a joint-venture, the retailer brand market share of Tesco Korea has continuously increased. It would be expected that Tesco UK has helped Tesco Korea to settle down in the Korean market. During interviews with Tesco and a Tesco supplier, the researcher found that Tesco Korea has obviously taken an advantage of retailing know-how created by Tesco UK. Furthermore, the retailer brand development and handling process of Tesco Korea has been operated with the help of Tesco UK. This might mean that Tesco UK has directly or indirectly an impact on the improvement of Korean retailer brand development skills. As a mechanism to transfer retailing knowledge developed in the home market into the host market, one of the international retailers, Tesco UK has adopted many different ways such as annual meeting, trading meeting to import or export own retailer brand products, offering of operation manual developed by Tesco UK and buyer cooperation between Tesco UK and Korea, in order to share information. Through these communication techniques, the knowledge of Tesco UK has been transferred to Tesco Korea. This research accordingly suggests that retailer brand market share is apparently related to how sophisticated or advanced the knowledge of the retailer brand development and handling process of retailers are. It is also demonstrated by this research that advanced development and handling skills make a considerable contribution to increasing retailer brand share in markets with a lower share or no presence of retailer brands.

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Resear cher & Coordinator, Canal Reseach & Development, japan (농업수리시설과 소수로굴착용 Trencher V형의 개발에 대하여)

  • 영목청
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.21 no.2
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    • pp.28-36
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    • 1979
  • One of most important problems in the Monsoon Asia today is the production of rice paddy to meet the needs of the ever increasing population. Diversemeans are being employed to meet this demand, both by increasing productivity of existing farm land and by bringing further areas into cultivation. The primary step in either field is to ensure that there is sufficient moisture in the soil to suit the paddy, and at the same this means that excess moisture has to be drained off the land, while in others irrigat ion has to be employed to bring sufficient water to an area. In view of the fact that the project comprises a huge amount of earthwork, it can be carried out by extensive use of construction machinery in order to shorten the period. As farm ditch has a comparatively small section with shallow cutting depth, inaddition, there is lack of access road in the field, the excavation equipment with bulldozer or tracter-shovel (backhoe) type are not applicable because there are mostly adapted for the excavation of deep and wide section. Mini-backhoe with its bucket width not larger than 0. 3m, and width of blade not larger than 1. 00m seems to be more adaptable. About 80% of excavation of ditch section will be done by the machinery while the other 20% of excavation together with the finishing of the section are supposed to be done by man-power. The embankment of ditch section can be compacted by the crawler of backhoe when it is moving along the ditch for excavation. However, Lowland paddy field in the Monsoon Asia are made particulary in rain season, therefore, heavy machinery is not easy excavation for ditch. It is very important to know exact ground support power of the working site and select machines with corresponding ground pressure. Ground support power is variable subject to quality and water content of soil and therefore selection of machines should be made duly considering ground condition of the site at the time of construction works. Farm ditches dug and compacted by mannual labar are of poor quality and subject to destruction after one or two years of operation. On the other hand, excavation and compaction by bulldozer is not practical for ditches. Backboe is suitable for slope land, but this is required cycle time of bucket excavation and dumped out. If a small-scale farm ditch trencher adaptable to lowland paddy field is invented, such a machine could greatly accelerate the massive construction work envisaged in many countries and thus significantly speed up the most difficult part of irrigation development and management in Monsoon Asia.

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