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Combined Effect of Ganciclovir and Vidarabine on the Replication, DNA Synthesis, and Gene Expression of Acyclovir-resistant Herpes Simplex Virus (Acyclovir저항성 Herpes Simplex Virus의 복제, DNA합성 및 형질 발현에 미치는 Ganciclovir 및 Vidarabine의 병용효과에 관한 연구)

  • Yang, Young-Tai;Cheong, Dong-Kyun;Mori, Masakazu
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.115-134
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    • 1989
  • Combined effects of ganciclovir (GCV) and vidarabine (ara-A) on the replication, DNA synthesis, and gene expression of wild type-1 herpes simplex virus (HSV-1) and three acyclovir (ACV)-resistant HSV-1 mutants were studied. These mutants include a virus expressing no thymidine kinase $(ACV^r)$, a virus expressing thymidine kinase with altered substrate specificity $(IUdR^r)$, and a mutant expressing altered DNA polymerase $(PAA^r5)$. GCV, an agent activated by herpesvirus specific thymidine kinase, showed potent antiviral activity against the wild type HSV-1(KOS) and DNA polymerase mutant $(PAA^r5)$. The ACV-resistant mutants with thymidine kinase gene $(ACV^r\;and\;IUdR^r)$ were resistant to GCV. All tested wild type HSV-1 or ACV-resistant HSV-1 mutants did not display resistance to vidarabine (are-A). Combined GCV and ara-A showed potentiating synergistic antiviral activity against wild type KOS and $PAA^r5$, and showed subadditive combnined ativiral activity against thymidine kinase mutants. Combined GCV and ara-A more significantly inhibited the viral DNA synthesis in wild type KOS and $PAA^r5-infected$ cells to a greater extent than either agent alone, but the synergism was not determined in $ACV^r$ or $IUdR^r-infected$ cells. These data clearly indicate that combined GCV and ara-A therapy might be useful for the treatment of infections caused by wild type HSV-1 or ACV-resistant HSV-1 with DNA polymerase mutation. ACV-resistant viruses with the mutation in thymidine kinase gene are also, resistant to GCV, but susecptible to ara-A, indicating that ara-A would the drug of choice for the treatment of ACV-resistant HSV-1 which does not express thymidine kinase or expresses thymidine kinase with altered substrate specificity. While the synthesis of viral ${\alpha}-proteins$ of wild type HSV-1 was not affected by ACV, GCV, ara-A, or combined GCV and ara-A, the synthesis of ${\beta}-proteins$ was slightly but significantly increased at the later stage of viral infection by the antiviral agents. The synthesis of ${\gamma}-proteins$ of wild type HSV- 1 was significantly inhibited by ACV, GCV, ara-A, and combined GCV and ara-A. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ also significantly altered the expression of viral ${\beta}-and$ ${\gamma}-proteins$, of which efffct was similar to that of GCV $(10-{\mu}M)$ alone. Although ACV at the concentration of $10-{\mu}M$ did not alter the expression of ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ of ACV-resistant $PAA^r5$, GCV and ara-A significantly alter the epression of ${\beta}-and$ ${\gamma}-proteins$, not ${\alpha}-protein$, as same manner as they altered the expression of those proteins in cells inffcted with wild type HSV-1. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ altered the expression ${\beta}-and$ ${\gamma}-proteins$ in $PAA^r5$ infected cells, and the effect of combined regimen was comparable of that of GCV $(10-{\mu}M)$. These data indicate that the alteration in the expression of ${\beta}-and$ ${\gamma}-proteins$ in wild type HSV-1 or $PAA^r5$ infected cells could be more significantly affected by combined GCV and are-A than individual GCV or ara-A. In view of the fact that (a) viral ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ are synthesized in a cascade manner; (b) ${\beta}-proteins$ are essential for the synthesis of viral DNA; (c) the synthesis of ${\beta}-proteins$ are inhibited by ${\gamma}-proteins$; and (d) most ${\gamma}-proteins$ are made from the newly synthesized progeny virus, it is suggested that GCV and ara-A, alone or in combination, primarily inhibit the synthesis of viral DNA, and by doing so might exhibit their antiherpetic activity. The alteration in viral protein synthesis in the presence of tested antiviral agents could result from the alteration in viral DNA synthesis. From the present study, it can be concluded that (a) combined GCV and ara-A therapy would be beneficial for the control of inffctions caused by wild type HSV-1 or ACV-resistant DNA polymerase mutants; (b) the combined synergistic activity of GCV and ara-A is due to further decrease in the viral DNA by the combined regimen; (c) ara-A is the drug of choice for the infection caused by ACV-resistant HSV-1 with thymidine kinase mutation; and (d) the alteration in viral protein synthesis by GCV and ars-A, alone or in combination, is mostly due to the decreased synthesis of viral DAN.

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An Empirical Study in Relationship between Franchisor's Leadership Behavior Style and Commitment by Focusing Moderating Effect of Franchisee's Self-efficacy (가맹본부의 리더십 행동유형과 가맹사업자의 관계결속에 관한 실증적 연구 - 가맹사업자의 자기효능감의 조절효과를 중심으로 -)

  • Yang, Hoe-Chang;Lee, Young-Chul
    • Journal of Distribution Research
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    • v.15 no.1
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    • pp.49-71
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    • 2010
  • Franchise businesses in South Korea have contributed to economic growth and job creation, and its growth potential remains very high. However, despite such virtues, domestic franchise businesses face many problems such as the instability of franchisor's business structure and weak financial conditions. To solve these problems, the government enacted legislation and strengthened franchise related laws. However, the strengthening of laws regulating franchisors had many side effects that interrupted the development of the franchise business. For example, legal regulations regarding franchisors have had the effect of suppressing the franchisor's leadership activities (e.g. activities such as the ability to advocate the franchisor's policies and strategies to the franchisees, in order to facilitate change and innovation). One of the main goals of the franchise business is to build cooperation between the franchisor and the franchisee for their combined success. However, franchisees can refuse to follow the franchisor's strategies because of the current state of franchise-related law and government policy. The purpose of this study to explore the effects of franchisor's leadership style on franchisee's commitment in a franchise system. We classified leadership styles according to the path-goal theory (House & Mitchell, 1974), and it was hypothesized and tested that the four leadership styles proposed by the path-goal theory (i.e. directive, supportive, participative and achievement-oriented leadership) have different effects on franchisee's commitment. Another purpose of this study to explore the how the level of franchisee's self-efficacy influences both the franchisor's leadership style and franchisee's commitment in a franchise system. Results of the present study are expected to provide important theoretical and practical implications as to the role of franchisor's leadership style, as restricted by government regulations and the franchisee's self-efficacy, which could be needed to improve the quality of the long-term relationship between the franchisor and franchisee. Quoted by Northouse(2007), one problem regarding the investigation of leadership is that there are almost as many different definitions of leadership as there are people who have tried to define it. But despite the multitude of ways in which leadership has been conceptualized, the following components can be identified as central to the phenomenon: (a) leadership is a process, (b) leadership involves influence, (c) leadership occurs in a group context, and (d) leadership involves goal attainment. Based on these components, in this study leadership is defined as a process whereby franchisor's influences a group of franchisee' to achieve a common goal. Focusing on this definition, the path-goal theory is about how leaders motivate subordinates to accomplish designated goals. Drawing heavily from research on what motivates employees, path-goal theory first appeared in the leadership literature in the early 1970s in the works of Evans (1970), House (1971), House and Dessler (1974), and House and Mitchell (1974). The stated goal of this leadership theory is to enhance employee performance and employee satisfaction by focusing on employee motivation. In brief, path-goal theory is designed to explain how leaders can help subordinates along the path to their goals by selecting specific behaviors that are best suited to subordinates' needs and to the situation in which subordinates are working (Northouse, 2007). House & Mitchell(1974) predicted that although many different leadership behaviors could have been selected to be a part of path-goal theory, this approach has so far examined directive, supportive, participative, and achievement-oriented leadership behaviors. And they suggested that leaders may exhibit any or all of these four styles with various subordinates and in different situations. However, due to restrictive government regulations, franchisors are not in a position to change their leadership style to suit their circumstances. In addition, quoted by Northouse(2007), ssubordinate characteristics determine how a leader's behavior is interpreted by subordinates in a given work context. Many researchers have focused on subordinates' needs for affiliation, preferences for structure, desires for control, and self-perceived level of task ability. In this study, we have focused on the self-perceived level of task ability, namely, the franchisee's self-efficacy. According to Bandura (1977), self-efficacy is chiefly defined as the personal attitude of one's ability to accomplish concrete tasks. Therefore, it is not an indicator of one's actual abilities, but an opinion of the extent of how one can use that ability. Thus, the judgment of maintain franchisee's commitment depends on the situation (e.g., government regulation and policy and leadership style of franchisor) and how it affects one's ability to mobilize resources to deal with the task, so even if people possess the same ability, there may be differences in self-efficacy. Figure 1 illustrates the model investigated in this study. In this model, it was hypothesized that leadership styles would affect the franchisee's commitment, and self-efficacy would moderate the relationship between leadership style and franchisee's commitment. Theoretically, quoted by Northouse(2007), the path-goal approach suggests that leaders need to choose a leadership style that best fits the needs of subordinates and the work they are doing. According to House & Mitchell (1974), the theory predicts that a directive style of leadership is best in situations in which subordinates are dogmatic and authoritarian, the task demands are ambiguous, and the organizational rule and procedures are unclear. In these situations, franchisor's directive leadership complements the work by providing guidance and psychological structure for franchisees. For work that is structured, unsatisfying, or frustrating, path-goal theory suggests that leaders should use a supportive style. Franchisor's Supportive leadership offers a sense of human touch for franchisees engaged in mundane, mechanized activity. Franchisor's participative leadership is considered best when a task is ambiguous because participation gives greater clarity to how certain paths lead to certain goals; it helps subordinates learn what actions leads to what outcome. Furthermore, House & Mitchell(1974) predicts that achievement-oriented leadership is most effective in settings in which subordinates are required to perform ambiguous tasks. Marsh and O'Neill (1984) tested the idea that organizational members' anger and decline in performance is caused by deficiencies in their level of effort and found that self-efficacy promotes accomplishment, decreases stress and negative consequences like depression and emotional instability. Based on the extant empirical findings and theoretical reasoning, we posit positive and strong relationships between the franchisor's leadership styles and the franchisee's commitment. Furthermore, the level of franchisee's self-efficacy was thought to maintain their commitment. The questionnaires sent to participants consisted of the following measures; leadership style was assessed using a 20 item 7-point likert scale developed by Indvik (1985), self-efficacy was assessed using a 24 item 6-point likert scale developed by Bandura (1977), and commitment was assessed using a 6 item 5-point likert scale developed by Morgan & Hunt (1994). Questionnaires were distributed to Korean optical franchisees in Seoul. It took about 20 days to complete the data collection. A total number of 140 questionnaires were returned and complete data were available from 137 respondents. Results of multiple regression analyses testing the relationships between the each of the four styles of leadership shown by the franchisor as independent variables and franchisee's commitment as the dependent variable showed that the relationship between supportive leadership style and commitment ($\beta$=.13, p<.001),and the relationship between participative leadership style and commitment ($\beta$=.07, p<.001)were significant. However, when participants divided into high and low self-efficacy groups, results of multiple regression analyses showed that only the relationship between achievement-oriented leadership style and commitment ($\beta$=.14, p<.001) was significant in the high self-efficacy group. In the low self-efficacy group, the relationship between supportive leadership style and commitment ($\beta$=.17, p<.001),and the relationship between participative leadership style and commitment ($\beta$=.10, p<.001) were significant. The study focused on the franchisee's self-efficacy in order to explore the possibility that regulation, originally intended to protect the franchisee, may not be the most effective method to maintain the relationships in a franchise business. The key results of the data analysis regarding the moderating role of self-efficacy between leadership behavior style as proposed by path-goal and commitment theory were as follows. First, this study proposed that franchisor should apply the appropriate type of leadership behavior to strengthen the franchisees commitment because the results demonstrated that supportive and participative leadership styles by the franchisors have a positive influence on the franchisee's level of commitment. Second, it is desirable for franchisor to validate the franchisee's efforts, since the franchisee's characteristics such as self-efficacy had a substantial, positive effect on the franchisee's commitment as well as being a meaningful moderator between leadership and commitment. Third, the results as a whole imply that the government should provide institutional support, namely to put the franchisor in a position to clearly identify the characteristics of their franchisees and provide reasonable means to administer the franchisees to achieve the company's goal.

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A Comparative Study on Buddhist Painting, MokWooDo (牧牛圖: PA Comparative Study on Buddhist Painting, MokWooDo (牧牛圖: Painting of Bull Keeping) and Confucian/Taoist Painting, SipMaDo (十馬圖: Painting of Ten Horses) - Focused on SimBeop (心法: Mind Control Rule) of the Three Schools: Confucianism, Buddhism and Taoism -nd Control Rule) of the Three Schools: Confucianism, Buddhism and Taoism - (불가(佛家) 목우도(牧牛圖)와 유·도(儒·道) 십마도(十馬圖) 비교 연구 - 유불도(儒佛道) 삼가(三家)의 심법(心法)을 중심으로 -)

  • Park, So-Hyun;Lee, Jung-Han
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.40 no.4
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    • pp.67-80
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    • 2022
  • SipWooDo (十牛圖: Painting of Ten Bulls), a Buddhist painting, is a kind of Zen Sect Buddhism painting, which is shown as a mural in many of main halls of Korean Buddhist temples. MokWooDo has been painted since Song Dynasty of China. It paints a cow, a metaphor of mind and a shepherd boy who controls the cow. It comes also with many other types of works such as poetry called GyeSong, HwaWoonSi and etc. That is, it appeared as a pan-cultural phenomenon beyond ideology and nation not limited to Chinese Buddhist ideology of an era. This study, therefore, selects MokWooDo chants that represent Confucianism, Buddhism and Taoism to compare the writing purposes, mind discipline methods and ultimate goals of such chant literatures in order to integrate and comprehend the ideologies of such three schools in the ideologically cultural aspect, which was not fully dealt with in the existing studies. In particular, the study results are: First, the SipWooDo of Buddhist School is classified generally into Bo Myoung's MokWooDo and Kwak Ahm's SimWooDo (尋牛圖: Painting of Searching out a Bull). Zen Sect Buddhism goes toward nirvana through enlightenment. Both MokWooDo and SimWooDo of Buddhist School are the discipline method of JeomSu (漸修: Discipline by Steps). They were made for SuSimJeungDo (修心證道: Enlightenment of Truth by Mind Discipline), which appears different in HwaJe (畫題: Titles on Painting) and GyeSong (偈頌: Poetry Type of Buddhist Chant) between Zen Sect Buddhism and Doctrine Study Based Buddhism, which are different from each other in viewpoints. Second, Bo Myoung's MokWooDo introduces the discipline processes from MiMok (未牧: Before Tamed) to JinGongMyoYu (眞空妙有: True Vacancy is not Separately Existing) of SsangMin (雙泯: the Level where Only Core Image Appears with Every Other Thing Faded out) that lie on the method called BangHalGiYong (棒喝機用: a Way of Using Rod to Scold). On the other side, however, it puts its ultimate goal onto the way to overcome even such core image of SsangMin. Third, Kwak Ahm's SimWooDo shows the discipline processes of JeomSu from SimWoo (尋牛: Searching out a Bull) to IpJeonSuSu (入鄽垂手: Entering into a Place to Exhibit Tools). That is, it puts its ultimate goal onto HwaGwangDongJin (和光同塵: Harmonized with Others not Showing your own Wisdom) where you are going together with ordinary people by going up to the level of 'SangGuBori (上求菩提: Discipline to Go Up to Gain Truth) and HaHwaJungSaeng (下化衆生: Discipline to Go Down to Be with Ordinary People)' through SaGyoIpSeon (捨敎入禪: Entering into Zen Sect Buddhism after Completing a Certain Volume of Doctrine Study), which are working for leading the ordinary people of all to finding out their Buddhist Nature. Fourth, Shimiz Shunryu (清水春流)'s painting YuGaSipMaDo (儒家十馬圖: Painting of Ten Horses of Confucian School) borrowed Bo Myoung's MokWooDo. That is, it borrowed the terms and pictures of Buddhist School. However, it features 'WonBulIpYu (援佛入儒: Enlightenment of Buddhist Nature by Confucianism)', which is based on the process of becoming a greatly wise person through Confucian study to go back to the original good nature. From here, it puts its goal onto becoming a greatly wise person, GunJa who is completely harmonized with truth, through the study of HamYang (涵養: Mind Discipline by Widening Learning and Intelligence) that controls outside mind to make the mind peaceful. Its ultimate goal is in accord with "SangCheonJiJae, MuSeongMuChee (上天之載, 無聲無臭: Heaven Exists in the Sky Upward; It is Difficult to Get the Truth of Nature, which has neither sound nor smell)' words from Zhōngyōng. Fifth, WonMyeongNhoYin (圓明老人)'s painting SangSeungSuJinSamYo (上乘修真三要: Painting of Three Essential Things to Discipline toward Truth) borrowed Bo Myoung's MokWooDo while it consists of totally 13 sheets of picture to preach the painter's will and preference. That is, it features 'WonBulIpDo (援佛入道: Following Buddha to Enter into Truth)' to preach the painter's doctrine of Taoism by borrowing the pictures and poetry type chants of Buddhist School. Taoism aims to become a miraculously powerful Taoist hermit who never dies by Taoist healthcare methods. Therefore, Taoists take the mind discipline called BanHwanSimSeong (返還心性: Returning Back to Original Mind Nature), which makes Taoists go ultimately toward JaGeumSeon (紫金仙) that is the original origin by changing into a saint body that is newly conceived with the vital force of TaeGeuk abandoning the existing mind and body fully. This is a unique feature of Taoism, which puts its ultimate goal onto the way of BeopShinCheongJeong (法身淸淨: Pure and Clean Nature of Buddha) that is in accord with JiDoHoiHong (至道恢弘: Getting to Wide and Big Truth).