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Effects of Site-Mutagenesis of an Amino Acid Triplet Repeat at $M_1$ and $M_2$ Muscarinic Receptors on Receptor Function ($M_1$$M_2$ 무스카린성 수용체에서 아미노산 Triplet Repeat의 Site-Mutagenesis가 수용체기능에 미치는 영향)

  • Lee, Seok-Yong;Lee, Sang-Bok
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.311-321
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    • 1996
  • Both $M_1$ and $M_2$ muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T) at C-terminus ends of the second putative transmembrane domains. This triplet is repeated as LYT-LYT in $M_2$ receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposed fashion (LYT-TYL) in the sequence of $M_1$ receptors. In this work, we employed site-directed mutagenesis to investigate the possible significance of this unique sequence diversity for determining the distinct differential cellular function at the two receptor subtypes. Mutation of the LYTTYL sequence of $M_1$ receptors to the corresponding $M_2$ receptor LYTLYT sequence did not result in a significant change in the binding affinity of the agonist carbachol. The reverse mutation at the $M_2$ receptor also did not modify agonist affinity. Surprisingly, the LYTLYT $M_1$ receptor mutant demonstrated markedly enhanced coupling to activation of phospholipase C without a change in its coupling to increased cyclic AMP formation. There was also an enhanced receptor sensitivity in transducing elevation of intracellular $Ca^{2+}$. On the other hand, the reverse $LYTLYT{\rightarrow}LYTTYL$ mutation in the $M_2$ receptor did not alter its coupling to inhibition of adenylate cyclase, but slightly enhanced its coupling to stimulation of phosphoinositide (PI) hydrolysis. Our data suggest that the LYTTYL/LYTLYT sequence differences between $M_1$ and $M_2$ muscarinic receptors are not important for specifying ligand binding and coupling of various subtypes of muscarinic receptors to different cellular signaling pathways although they might play a role in the modulation of muscarinic reseptor coupling to PI hydrolysis.

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The Effect of Welfare Recognition on the Utilization of Social Services and the Satisfaction of Social Welfare Policies for the Elderly (노인의 복지인식이 사회서비스 이용과 사회복지정책 만족도에 미치는 영향)

  • Seo, Bok Hyun;Hwang, Yoon Hee
    • The Journal of the Korea Contents Association
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    • v.20 no.8
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    • pp.583-597
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    • 2020
  • This study analyzed how elderly people's perception of social welfare affects social welfare service and social welfare policy satisfaction by paying attention to the use of social welfare services and satisfaction with social welfare policies. In order to achieve this research goal, 465 people aged 60 or older who completed responses to the additional survey were collected and analyzed as research targets based on data from the Korea Welfare Panel, which is accumulated by the Korea Institute for Health and Social Affairs and Seoul National University's Social Welfare Research Institute. The results of this study are as follows. First, "Awareness of welfare for the elderly (recognition of welfare expenditure, recognition of welfare targets, recognition of welfare tax increases)" was found to have a negative impact on "use of social services." Second, "Awareness of welfare for the elderly (recognition of welfare expenditure, recognition of welfare targets, recognition of welfare tax increases)" was found to have a negative impact on "satisfaction with social welfare policies." Third, the impact of the recognition of welfare for the elderly on the use of social services was found to be different according to the demographic characteristics (education level, income level, educational background, gender). Fourth, according to the "population statistical characteristics (education level, income level, educational background, gender)" the impact of the recognition of welfare for the elderly on the satisfaction of social welfare policy was shown to be different. The implications of this study are that we looked at multi-dimensional welfare awareness and social service use experience together as factors affecting social welfare policy satisfaction. In other words, it is meaningful that the government focused on welfare awareness based on individual values and subjective perceptions as an influence on social welfare policy satisfaction, and sought practical alternatives to welfare policies and welfare sites by examining whether the experience of using social services in relation to welfare awareness and social welfare policy satisfaction among the elderly.

Simultaneous Analysis for Veterinary Drug Residues in Honey by HPLC/MS/MS (HPLC-MS/MS를 이용한 벌꿀 중 동물용의약품 동시분석방법 연구)

  • Kim, Jong-Hwa;Moon, Sun-Ea;Kim, Ki-Yu;Jung, You-Jung;Lee, Chang-Hee;Ku, Eun-Jung;Yoon, Mi-Hye;Lee, Jong-Bok
    • Journal of Food Hygiene and Safety
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    • v.31 no.2
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    • pp.94-98
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    • 2016
  • This study was conducted to establish the simultaneous analysis method for veterinary drug residues in honey by high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). The eleven targeting veterinary drugs with honey test method in Korean Food Standards Codex were divided into Group 1 (streptomycine dihydrostreptomycine, neomycine) and Group 2 (oxytetracycline, enrofloxacin, ciprofloxacin, cymiazole, chloramphenicol, amitraz, coumaphos, fluvalinate) to be analyzed simultaneously. From the results, the retention time (RT) of the targeting drugs was within 15 min, the range of detection limits was 0.0056 to $0.0643{\mu}g/g$ and the range of quantification limits was 0.0169 to $0.1948{\mu}g/g$. The coefficients of determination ($R^2$) for Group 1 ($0.05{\sim}1.0{\mu}g/mL$) and Group 2 ($0.01{\sim}1.0{\mu}g/mL$) were 0.9917~0.9987 and 0.9923~1.000 respectively, and showed the good linearity. The recovery rates for Group 1 (final conc. $0.25{\mu}g/g$) and Group 2 (final conc. $1.0{\mu}g/g$) were 65.1~80.6% and 64.2~90.3% respectively. Also, the analysis results of inter day (n = 3) and intra day (n = 6) RSD (%) for area and retention time showed that the RSD (%) for area and retention time was below 10.92% and 1.57%. Therefore, the simultaneous analysis method of this study is evaluated to be a good test method for veterinary drug residues in honey.

Net Shapes of the Model Pound net according to Added Sinker - In case of the upperward flow with fish court net - (부가중량추에 따른 모형 정치망의 형상변화 - 운동장이 湖上側인 경우 -)

  • Yun, Il-Bu;Lee, Ju-Hee;Kwon, Byeong-Guk;Yoo, Jae-Bum;Cho, Young-Bok
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.41 no.1
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    • pp.17-26
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    • 2005
  • There are several problems in the commercial pound net in the heavy tide ; the breaking and loss of net, steeply variation of net shape and decreasing of fishing efficiency, etc. In order to solve these problems, we introduced method of added sinker used to coastal cultivating cage of Japan and investigated the possibility of application to the Korean pound net. The results are obtained as follows; 1. In case of the upperward flow with fish court net, tension of the frame line was increased about 10${\sim}$25% than that of prototype according to the added sinker from 1.3gf to 5.2gf. The tension of A-type and B-type was similar to the case of the prototype, the tension of C-type and D-type was increased about 10${\sim}$15% than that of prototype. 2. The variation of deformed angle of fish court net was from 0$^{\circ}$ to 70$^{\circ}$ and that of the slope net was from 0$^{\circ}$ to 64$^{\circ}$ and that of the second bag net was from 0$^{\circ}$ to 46$^{\circ}$ and the depth of the second bag net was increased about 10% when the added sinker was changed from 1.3gf to 5.2gf. The depth of the first bag net and the second bag net were decreased about 50% than that of initial depth. 3. For the deformed angle of fish court net according to the attached point of the added sinker, A-type and B-type were decreased about 25% and 10% than the prototype, respectively. C-type was similar to the case of the prototype and D-type was increased about 15% than that of the prototype. The depth of slope net became deep in turn of A-type, B-type, C-type and D-type. For the depth of the second bag net, A-type, B-type, C-type and D-type were increased about 10${\sim}$15% than that of prototype. The depth of the slope net was changed from 0$^{\circ}$ to 63$^{\circ}$ and that of the second bag net was changed from 0${\sim}$44$^{\circ}$ according to the increase of velocity. 4. The optimal weight of added sinker was about 2.6${\sim}$3.6gf and the optimal attached point of added sinker was the case of C-type and D-type.

In vitro and in vivo Effects of Extracts of Lentinus edodes on Tumor Growth in a Human Papillomavirus 16 Oncogenes-transformed Animal Tumor Model -Apoptosis-mediated Tumor Cell Growth Inhibition- (자궁경부암동물세포에서 표고버섯의 in vitro 및 in vivo 항암효과 -Apoptosis에 의한 종양세포주의 성장억제-)

  • Park, Jeong-Min;Lee, Sung-Hyun;Kim, Jung-Ok;Park, Hong-Ju;Park, Jae-Bok;Sin, Jeong-Im
    • Korean Journal of Food Science and Technology
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    • v.36 no.1
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    • pp.141-146
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    • 2004
  • Fungal products indirectly mediate anti-tumor effects in vitro and in vivo. To investigate whether Lentinus edodes might possess direct anti-tumor substance, L. edodes was extracted and tested on human papillomavirus (HPV) 16 oncogenes-associated animal tumor cells (TC-1) and in an animal tumor model. Only water extract displayed direct anti-proliferative effects in TC-1 tumor cells in vitro. This inhibition was dose-dependent, and inhibitory concentration ($IC_{50}$) was $800\;{\mu}g/mL$. Fungal extracts also showed growth inhibition to human cervical cancer cells (CaSki and HeLa) similarly to TC-1 tumor cells. When fungal extracts were added at a high dose (1.5 mg/mL), cell growth was inhibited within 6 hr following extract treatment. Cell growth inhibition was blocked by heat treatment, but not by low pH, which is indicative of heat sensitivity of this anti-proliferative substance. Cell growth suppression was mediated by apoptosis, as determined by Annexin V and propidium iodide staining. When challenged with TC-1 cells, direct intratumoral injection of fungal extracts resulted in some positive effect on tumor growth inhibition, as compared to oral delivery. Results suggest that heat labile substance of L. edodes suppresses growth of HPV oncogenes-associated tumor cells through apoptosis.

The Effects of Aroma Self Massage in Hands on Pain, Depressive Mood and Anxiety in Breast Cancer Patients (유방암 환자의 통증, 우울 및 불안 증상 조절에 아로마 자가 치료의 효과)

  • Sohn, Keun-Joo;Kim, Myung-Ja;Lee, June-Young;Lee, Jae-Bok;Kim, Su-Hyun;Kim, Jong-A;Jung, Hoe-Hyun;Choi, Seung-Wan;Choi, Youn-Seon
    • Journal of Hospice and Palliative Care
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    • v.8 no.1
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    • pp.18-29
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    • 2005
  • Purpose: Aroma therapy is one modality of alternative medicine. It was well known to have an analgesic, antidepressive and anxiolytic effects. This study is designed to investigate the effect of aroma self hand massage on vital signs, pain, depression, anxiety and stress in breast cancer patients. Methods: 32 female patient over 20 years old were divided into two groups by a non-blinded randomized controlled method. Patient in the aroma group (n=15) massaged their hands twice a day using aroma oil by themselves in their home for 2 weeks. However, those in control group (n=17) had not received my intervention during the study periods. Pain intensity, state anxiety, depression and stress of subjects were evaluated three times (0, 1, 3 weeks) using Visual Analogue Scale (VAS, $0{\sim}10cm$), State Trait Anxiety Inventory (STAI), Beck Depression Inventory Scales (BDIS), Brief Encounter Psychosocial Instrument (BEPSI revised edition). Also the change of patients' accompanying symptoms after aroma massage were analyzed using a structured questionnaire. Results: Pain Intensity decreased in the aroma group compared with control group (VAS changes $-0.83{\pm}1.01\;vs\;0.38{\pm}0.86$, P=0.005). The numbers of accompanying symptoms (P=0.044), depression score (P=0.001) and anxiety score (P=0.008) were significantly decreased in the aroma group, while in control group they increased after 2 weeks. However, the stress score showed no significant changes in both groups ($0.05{\pm}0.85\;vs\;0.04{\pm}0.20$, P=0.1519). The depression, anxiety and stress score showed negative correlation with compliance of aroma massage, but statistically no significant. The systolic blood pressure was a little increased in aroma group ($4.53{\pm}14.43\;vs\;0.0{\pm}7.22$, P=0.026), but was not significant clinically. Patients in the aroma group complained of several symptoms such as headache (20%), paresthesia (6.75%) and nausea (6.7%). However, there were no drop-out patients for those side effects. Conclusion: Aroma self massage during two weeks in breast cancer patients alleviates the pain intensity, depression and anxiety significantly.

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Risk Factors for the Early Recognition of Cow's Milk Protein-induced Enterocolitis (우유 단백질 유발성 장염의 조기진단을 위한 위험인자)

  • Lee, Sung Hyuk;Choi, Seon Yun;Lee, Byung Cheol;Choi, Won Joung;Choe, Byung Kyu;Kim, Yeo Hyang;Kang, Una;Kam, Sin;Hwang, Jin-Bok
    • Clinical and Experimental Pediatrics
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    • v.48 no.9
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    • pp.991-997
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    • 2005
  • Purpose : Cow's milk protein-induced enterocolitis(CMPIE) is a symptom complex of vomiting and/or diarrhea caused by delayed hypersensitivity and may result in serious complications. This study was undertaken to identify high risk factors to facilitate the early recognition of CMPIE. Methods : We reviewed the data of 101 patients, aged 15 to 45 days, admitted due to vomiting and/or diarrhea between 2003 and 2004. After excluding 13 patients absolutely breast-fed and 2 patients transferred from other hospitals with the impression of CMPIE, the 86 study subjects were divided into three groups based on the underlying etiologies; CMPIE, infectious and non-infectious group. Results : CMPIE was diagnosed in 11 patients(12.8%). On admission, failure to gain weight(P=0.003), hypoalbuminemia(P=0.003), peripheral leukocytosis(P=0.015), and metabolic acidosis(P=0.014) were more significant in the CMPIE group than in the others. Multiple logistic regression analysis showed that the independent predictors of high risks for CMPIE were failure to gain weight <10 g/day(OR, 10.25[95% CI, 1.62-65.06]) and serum hypoalbuminemia <3.5 g/dL(OR, 9.18[95% CI, 1.69-49.74]). Cow's milk challenges were performed in the 11 CMPIE patients; vomiting(81.8%), abnormal stool test(80.0%), peripheral leukocyte count and absolute neutrophil count(ANC) increase(100.0%) (P<0.05), and enteropathy(100.0%). Conclusion : CMPIE is not a rare clinical disease in early infancy. The high risk factors of CMPIE were identified as follow : failure to gain weight below 10 g/day, hypoalbuminemia on admission and a rapid decrease during admission. Cow's milk challenge test with endoscopic duodenal biopsy was helpful to confirm CMPIE.

Bioequivalence of Burophil Capsule to Surfolase Capsule (Acebrophylline 100 mg) (설포라제 캡슐(아세브로필린 100 mg)에 대한 부로필 캡슐의 생물학적 동등성)

  • Cho, Hea-Young;Park, Eun-Ja;Kang, Hyun-Ah;Kim, Se-Mi;Park, Chan-Ho;Oh, In-Joon;Lim, Dong-Koo;Lee, Myung-Hee;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.35 no.3
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    • pp.179-185
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    • 2005
  • Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

Bioequivalence of SCD Zaltoprofen Tablet to Soleton® Tablet (Zaltoprofen 80 mg) (솔레톤 정(잘토프로펜 80 mg)에 대한 삼천당잘토프로펜 정의 생물학적동등성)

  • Kang, Hyun-Ah;Park, Sun-Ae;Kim, Dong-Ho;Kim, Hwan-Ho;Yun, Hwa;Kim, Kyng-Ran;Yoo, Hee-Doo;Park, Eun-Ja;Cho, Hye-Young;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.36 no.3
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    • pp.209-215
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    • 2006
  • Zaltoprofen, (2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid) is an NSAID with powerful anti-inflammatory effects as well as an analgesic action on inflammatory pain. The purpose of the present study was to evaluate the bioequivalence of two zaltoprofen tablets, $Soleton^{\circledR}$ (CJ Corp.) and SCD Zaltoprofen (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of zaltoprofen from the two zatoprofen formulations in vitro was tested using KP Vlll Apparatus ll method with various dissolution media. Twenty six healthy male subjects, $23.2{\pm}2.26$ years in age and$64.7{\pm}8.08$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 80 mg as zaltoprofen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of zaltoprofen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Soleton^{\circledR}$ were 6.33, 5.91 and 17.7% for $AUC_t$, $C_{max}$ and untransformed $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,log $1.01{\sim}1og\;1.11$ and log $0.928{\sim}1og\;1.18$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating SCD Zaltoprofen tablet was bioequivalent to $Soleton^{\circledR}$ tablet.

Studies on Characteristics of Natural Shell Sand as a Soil Amendment (자연패사(自然貝砂)의 특성(特性)과 토양산도(土壤酸度) 교정력(矯正力)에 관(關)한 연구(硏究) -(제주도(濟州道) 및 진도산(珍島産을) 중심(中心)으로)-)

  • Lee, Yun-Hwan;Han, Ki-Hak;Park, Young-Dae;Kim, Bok-Jin;Hur, Il-Bong
    • Applied Biological Chemistry
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    • v.15 no.3
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    • pp.241-249
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    • 1972
  • The characteristic and efficiency of natural shell sand in the coast of Cheju-Do and Jin-Do were studied to apply as agricultural lime for the soil acid adjustment. 1. The alkalinity of shell sand from Cheju coast was higher than that of Jindo and more weathered into fine particles. The particle size distributions of Cheju shell sand were condensed finer particles than 32 mesh in Cheju shell sands and in more coarser particles than 32 mesh in Jindo one. 2. The effect of Cheju shell sand on increasing soil pH value in the upland condition was low at the beginning but more gradually increased after 8 weeks from the treatment than ground lime, and Jindo was very dull during the period of treatment. The commercial lime crushed from Jindo was approximately equal to the ground lime. 3. In the submerged condition, the shell sand of Cheju reacted with soil acid more quickly than ground lime after 2 days, and Jindo was very slow. 4. The relative efficiency of various particle size fraction of the shell sand was superior to the ground lime. The lime particles between 9 to 14 mesh and 20 mesh had more remarkable difference of pH value than other fine particles. The efficiency among finer sizes than 20 mesh particle was approximately equal to each others. 5. The shell sand from the Cheju would be applied directly as agricultural lime without any treatment, and Jindo also can be expected to be effective as agricultural lime with crushing procedure.

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