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Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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경운성능(耕耘性能) 향상(向上)을 위한 쟁기 이체(犂體)의 적정(適正) 설계(設計)에 관(關)한 연구(硏究) -쟁기 이체곡면(犂體曲面)의 기하학적(幾何學的) 특성(特性)- (Optimum Design of Jaenggi(Korean plow) Bottoms to Improve the Tillage Performance(I) -The Geometrical Characteristics of the Jaenggi Bottoms-)

  • 정창주;한명범
    • Journal of Biosystems Engineering
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    • 제12권3호
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    • pp.30-41
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    • 1987
  • The geometrical shape of a plow bottom may be the most important factor affecting the performance of a plow for a given soil and operating conditions. There are various designs of the Jaenggi (Korean plow) available commercially, which may be different from each other and from the plow (Western plow) in respect to the shape and performance. This study was intended to investigate the geometrical characteristics of Jaenggi. The coordinate digitizer equipped with 3 potentiometers was designed and manufactured for measurement of the shape of curved plane of moldboard and share. The digitizer was connected to a microcomputer having the data acquisition system. This device was used to analyze the plow bottoms of 5 differently-made Jaenggis and one cylindrical plow. The results of the study are summarized as follows: 1. It was possible to measure easily and quickly the curved plane of plow bottom and to plot the view on three major plans using the coordinate digitizer electrically connected to a microcomputer system. 2. The shape of five Jaenggi bottoms analyzed could be characterized by the cutting angle having the range of $33-42^{\circ}$, the maximum share-lift angle of $41-50^{\circ}$, and the setting angle of moldboard wing of $46-70^{\circ}$. The most critical difference of the shape factors between the Jaenggi and the plow was found in the maximum share-lift angle, the former was more than twice as much as the latter. 3. The analysis of the shape of Jaenggi bottoms showed that the share projections on 3 major plans had a varied triangle, which was quite different from that of plow bottom. Especially, it was analyzed that the shape of furrow slice for the Jaenggi had a skewed rectangle, leaving a considerable height of the ridge at the furrow bottom. 4. The dihedral angle was similar range of $30-85^{\circ}$ for the all bodies investigated, but the directional angle was somewhat different from each other. The difference in directional angle was $5^{\circ}$ for the plow, $20^{\circ}$ for the Jaenggi A and $30^{\circ}$ for the Jaenggi B. 5. Area of the spherical representation region was 0.0328 for the plow, 0.1194 for the Jaenggi A and 0.1716 for the Jaenggi B. This may indicate that the plow came close to a working surface and the Jaenggi A and the Jaenggi B departed from a working surface to a somewhat greater extent.

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C대학교 대학생의 대학 몰입에 관한 탐색적 논의 (An Exploratory Study on Institutional Commitment of C-University Students)

  • 윤지원;이하정;박미라
    • 한국콘텐츠학회논문지
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    • 제21권8호
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    • pp.213-220
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    • 2021
  • 본 연구는 대학생의 대학 몰입에 영향을 주는 요인을 파악하여 재학생들의 대학 몰입을 높이기 위한 방안 모색의 기초자료를 마련하는 데에 목적이 있다. 자료 수집은 2020년 11월 19일부터 11월 26일까지 온라인 설문으로 진행하였고, 연구대상자는 경남 창원 소재의 C대학교 220명을 대상으로 하였다. 분석결과, 대학 몰입은 평균 3.30점이었고, 대학생활만족도는 평균 3.62점. 대학풍토는 평균 3.39점, 비교과프로그램만족도는 평균 3.48점으로 비교적 높게 나타났다. 대학 몰입은 대학생활만족도, 대학풍토, 비교과프로그램만족도와 순상관관계가 있었다(p<.001). 대상자의 대학 몰입에 가장 영향을 미치는 요인은 대학생활만족도였으며 그 다음으로 비교과프로그램만족도, 대학풍토 순이었다. 이 결과는 대학 몰입이 소속 전공 및 대학생활만족도, 대학풍토, 비교과프로그램만족도에 영향을 받으며, 특히 대학생활만족도의 영향력이 상대적으로 높아 대학 몰입을 높이기 위한 대학 차원의 노력이 필요함을 시사한다.

제조기업의 시장지향성이 품질경영활동과 경영성과에 미치는 영향에 관한 연구 (A Study on the Effects of the Manufacturer's Market Orientation on Quality Management activity and Business Performance)

  • 원유영;박종우;송광석;신호철
    • 유통과학연구
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    • 제11권6호
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    • pp.81-89
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    • 2013
  • Purpose - The market orientation of a manufacturer is a very critical competitive advantage factor in the development of new markets and the sustainability and maintenance of existing ones, achieved through the design of customer-oriented products. This is recognized as a virtuous circle, in which firms grow by means of promoting quality management. However, though market-oriented activities are important in management and operations, they seem to be promoted mainly by large-scale enterprises rather than by small- and medium-scale firms, the latter having invested relatively few company resources. Furthermore, few studies and analyses have examined how market orientation relates to the expansion of quality programs within organizations or with business performance; the market orientation and customer-orientation concepts are mixed together when both are used in research. Given the current market situation in which the servitization of manufacturing firms is rapidly expanding, this study's analysis of the effect on market orientation of manufacturers is a significant contribution. From this perspective, this study has several objectives. First, is to analyze and suggest the relationship between market orientation and quality management activity for manufacturers, focusing on three sub-activities: products, process, and quality management activities. Second, it is intended to identify correlation between manufacturers' market oriented activity and their management performance and then to analyze how market orientation affects business performance. The results of a number of prior studies on the correlation between market orientation and management performance have indicated that market orientation does affect management performance. Third, this study also investigates whether any differences in the relationship among market orientation, quality management activity and business performance occur according to company size. The results are used to present operational suggestions for large- and small- and medium-size firms. Research design, data, methodology - This study seeks to analyze and identify the causal features of the organic relationship among market orientation, quality management, and management performance for Korean manufacturing companies using three years (2005-2007) of market orientation, quality management, and business performance data. Subsequently, structural equation modeling was used to analyze the causal features of related factors and it aims to identify the features of market orientation, quality management, and business performance. Results - The analysis examined how market orientation affected the quality management and management performance of 159 smalland medium-size companies. In particular, enterprise quality management was analyzed in relation to management performance with a focus on activities such as leadership, measurement and improvement, quality control, cost management, and process management. Conclusions - The result of the analysis show that market orientation significantly affected all of the quality management activities and that market orientation in turn significantly affected organizational performance. The result of analysis indicate that quality management activities have a significant effect on quality control and cost management.

Distinct Involvement of 9p21-24 and 13q14.1-14.3 Chromosomal Regions in Raw Betel-Nut Induced Esophageal Cancers in the State of Meghalaya, India

  • Rai, Avdhesh K.;Freddy, Allen J.;Banerjee, Atanu;Kurkalang, Sillarine;Rangad, Gordon M.;Islam, Mohammad;Nongrum, Henry B.;Dkhar, Hughbert;Chatterjee, Anupam
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권6호
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    • pp.2629-2633
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    • 2012
  • Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.

식물 지방산 생산량의 증진을 위한 생명공학 연구현황 (Current biotechnology for the increase of vegetable oil yield in transgenic plants)

  • 이경렬;최윤정;김순희;노경희;김종범;김현욱
    • Journal of Plant Biotechnology
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    • 제38권4호
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    • pp.241-250
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    • 2011
  • 식물유의 거의 대부분은 triacylglycerol (TAG) 형태로 종자에 축적되어있으며 이는 종자가 발아할 때에 필수적인 에너지공급원이자 동물과 인간들에게 필수지방산과 중요한 에너지원이다. 최근 식용유의 건강기능성으로 수요증가와 더불어 바이오디젤과 산업원료 등의 산업적 수요도 증가함에 따라 더욱 중요한 자원이 되고 있다. 그래서 생명공학기술로 종자유의 함량을 증진하고자 하면 지질 생합성에 탄소의 유입에 관여하는 조절 유전자를 과발현 또는 억제하는 것이 결정적으로 중요하다. 본 총설에서는 지질함량에 영향을 미치는 것으로 여겨지는 후보 유전자들에 대해 기술하고 이들의 지방 함량 증대 가능성을 조사하였다. 식물의 지방산의 생합성과 종자유의 축적에 관여하는 유전자들은 크게 구분하자면 첫째, TAG가 생합성되기 위해 필요한 전구체를 합성하는 유전자, 둘째, 지방산합성과 TAG 축적에 관여하는 유전자, 셋째, 종자 발달과 종자유 축적에 관여하는 전사인자 유전자가 있다. 종자유 함량을 결정하는 대사들은 앞에서 언급했듯이 매우 복잡하기 때문에 최근에 전사인자의 조절이 다수의 지방생산 대사 유전자를 동시 조작하여 형질전환 식물에서 종자유 함량이 증진하는 것보다 더 바람직한 접근법으로 여겨지고 있다. 그러나 전사조절유전자의 과발현에 의해 나쁜 농업형질의 유도 같은 문제점도 해결해야 한다.

가금의 인공수정 (Artificial Insemination in Poultry)

  • Howarth, Birkett
    • 한국가축번식학회지
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    • 제7권2호
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    • pp.57-71
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    • 1983
  • 1. Diluted chicken semen can be preserved at 2 to 5$^{\circ}C$ for 24 to 48 hr with resultant fertility of greater than 90% of that of fresh semen. Turkey semen can be preserved at 10 to 15$^{\circ}C$ for 6 to 24 hr and provide economical fertility. 2. Frozen chicken semen has given variable results; a 21 to 93% fertility ranges as compared to 92 to 94% expected with fresh semen. Highest fertility levels obtained with frozen turkey semen intravaginally inseminated have been 61 and 63% using DMSO and glycerol, respectively, as cryoprotectants. 3. The use of glycerol as a cryoprotectant reauires that its concentration in semen be reduced to less than 2% either by dialysis or centrifugation after thawing and before intravaginal insemination if optimal fertility is to be obtained. 4. The temperature at which cryoprotectants are added to semen and the time allowed for equilibration are important for subsequent fertility pre- and post-freezing. 5. The type of container used for packaging the semen, freeze or cooling rates, thaw rates and level of cryoprotectant all interact in affecting cell survival. 6. Plastic freeze straws as a packaging device for semen offers the following advantages: easy to handle, require minimal storage space, offer a wide range of freeze and thaw rates, and insemination can be made directly from them upon thawing. 7. Controlled slow cooling rates of 1 to 8$^{\circ}C$/min have thus far provided the best results for cooling chicken semen throught the transition phase change (liquid to solid) or critical temperature range of +5 to -20 or -35$^{\circ}C$. 8. Highest fertilities have been achieved with frozen chicken semen where a slow thaw rate (2。 to 5$^{\circ}C$) has been used regardless of the freeze rate. 9. To maintain a constant high level of fertility throughout a breeding season with frozen semen, a higher absolute number of spermatozoa must be inseminated (2 to 3 times as many) as compared to fresh semen since a, pp.oximately 50% are destroyed during processing and freezing. 10. The quality of semen may vary with season and age of the male. Such changes in sperm quality could be accentuated by storage effects. Thus, the correct number of spermatozoa may very well vary during the course of a breeding period. 11. As to time of insemination, it is best to avoid inseminating chicken hens within 1-2 hr after or 3-5 hr before oviposition; and turkey hens during or 7-10 hr before oviposition. 12. The physiological receptiveness of the oviduct at the time of insemination is a very important biological factor influencing fertility levels throughout the breeding season.

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상, 하악골 유래 조골세포의 골형성 능: 일차 연구 (Osteogenic Response of Human Osteoblasts Derived from Mandible and Maxilla: A Preliminary Study)

  • 양훈주;송윤미;김리연;오지혜;조태형;김인숙;황순정
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제35권1호
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    • pp.31-37
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    • 2013
  • Purpose: Maxilla and mandible have different patterns of cortical and trabecular bone and different bone mineral densities, even though both are components of the jaw bone. However, cellular differences between maxilla- and mandible derived osteoblasts (OBs) have rarely been studied. We hypothesize that maxilla- and mandible-derived OBs show different responses to $17{\beta}$-estradiol (E2), which is one of the critical factors for bone formation. This study compares skeletal site-specific cell responses between maxilla- and mandible-derived human OBs to E2. Methods: Maxilla- and mandible-derived OBs derived from an identical donor were separately isolated from a total of five normal healthy subjects aged 18~44 years old, cultured with a treatment of 100 nM estrogen. The responses between maxilla- and mandible-derived OBs to E2 were evaluated and compared using cell proliferation, alkaline phosphatase (ALP) activity and gene expression of osteoprotegerin (OPG), ALP, insulin-like growth factor-1 (IGF-1), and estrogen receptor ${\alpha}$ ($ER{\alpha}$). Results: E2 did not have any distinct effects on the proliferation of both types of OBs. Mandible-derived OBs exhibited higher ALP activity than maxilla-derived OBs in the non-treated condition, which was common in all tested individuals. ALP activities of both types of OBs showed a minor increasing tendency with the treatment of E2, even though there was no statistical significance in some specimens. The gene expression of OB by E2 was diverse, depending on the individuals. There was increased expression of OPG, IGF-1, or $ER{\alpha}$ gene in the part of subjects, which was more repeated in maxilla-derived OBs. In particular, OPG or ALP induction by E appeared less frequently in mandible-derived OBs. Conclusion: Current results revealed that E2 affects maxilla- and mandible-derived OBs into facilitating the osteogenic process despite individual differences. Mandible-derived OBs are less sensitive to bone-forming gene expression by E2.

Ni/4H-SiC Field Plate Schottky 다이오드 제작 시 과도 식각에 의해 형성된 Nickel_Titanium 이중 금속 Schottky 접합 특성과 공정 개선 연구 (Characteristics of Nickel_Titanium Dual-Metal Schottky Contacts Formed by Over-Etching of Field Oxide on Ni/4H-SiC Field Plate Schottky Diode and Improvement of Process)

  • 오명숙;이종호;김대환;문정현;임정혁;이도현;김형준
    • 한국재료학회지
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    • 제19권1호
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    • pp.28-32
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    • 2009
  • Silicon carbide (SiC) is a promising material for power device applications due to its wide band gap (3.26 eV for 4H-SiC), high critical electric field and excellent thermal conductivity. The Schottky barrier diode is the representative high-power device that is currently available commercially. A field plate edge-terminated 4H-SiC was fabricated using a lift-off process for opening the Schottky contacts. In this case, Ni/Ti dual-metal contacts were unintentionally formed at the edge of the Schottky contacts and resulted in the degradation of the electrical properties of the diodes. The breakdown voltage and Schottky barrier height (SBH, ${\Phi}_B$) was 107 V and 0.67 eV, respectively. To form homogeneous single-metal Ni/4H-SiC Schottky contacts, a deposition and etching method was employed, and the electrical properties of the diodes were improved. The modified SBDs showed enhanced electrical properties, as witnessed by a breakdown voltage of 635 V, a Schottky barrier height of ${\Phi}_B$=1.48 eV, an ideality factor of n=1.04 (close to one), a forward voltage drop of $V_F$=1.6 V, a specific on resistance of $R_{on}=2.1m{\Omega}-cm^2$ and a power loss of $P_L=79.6Wcm^{-2}$.

걷기 프로그램 '걷쥬' 참여자의 여가만족이 건강증진행위 및 삶의 질에 미치는 영향 (Effects of Leisure Satisfaction on Health Promotion Behavior and Quality of Life of Participants In the Walking Program "Geod-Jyu")

  • 한치섭;김성민
    • 대한통합의학회지
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    • 제12권2호
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    • pp.121-131
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    • 2024
  • Purpose : This study aimed to investigate the leisure satisfaction of participants in the Geod-Jyu walking program and to examine the relationship between health promotion behaviors and quality of life. In addition, we investigated the impact of leisure satisfaction with walking among program participants on health promotion behaviors and quality of life. By clarifying these relationships, we aimed to identify factors of leisure satisfaction with walking that could enhance participants' health promotion behaviors and quality of life. Methods : A survey was conducted among 301 participants enrolled in the Geod-Jyu walking program in Chungcheongnam-do, with 288 responses analyzed. Data analysis included Pearson's correlation, confirmatory factor analysis, and multiple regression analysis using SPSS 27.0. Result : Leisure satisfaction exhibited a positive correlation with health promotion behavior (r=.544, p<.01) and quality of life (r=.478, p<.01). Furthermore, health promotion behavior showed a positive correlation with quality of life (r=.636, p<.01). Leisure satisfaction positively influenced quality of life, with physiological satisfaction (β=.16, t=2.32) and relaxation satisfaction (β=.15, t=2.04) emerging as notable contributors. In addition, leisure satisfaction had a significant positive impact on health promotion behaviors, with psychological satisfaction (β=.24, t=3.09) and educational satisfaction (β=.20, t=3.09) playing key roles. Health promotion behavior had a positive impact on quality of life, with all sub variables exhibiting significant positive effects in the following order: self-actualization (β=.24, t=4.16), stress management (β=.22, t=3.97), exercise (β=.22, t=4.05), and health responsibility (β=.12, t=2.14). Conclusion : The findings indicate that factors related to physical and rest satisfaction, as well as health-promoting behaviors facilitated by walking, significantly affected the quality of life among Geod-Jyu participants. Thus, promoting leisure satisfaction and engaging in health-promoting activities through walking can enhance overall well-being. Encouraging participation in the Geod-Jyu walking program is critical for physical and psychological benefits, and for promoting healthier behaviors. Further development of Geod-Jyu is expected to enhance walking satisfaction, promote self-care skills for health management, and positively influence quality of life.