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Anti-diabetic Effect of Crude Polysaccharides from Grifola frondosa in $KK-A^{y}$ Diabetic Mouse and 3T3-L1 Adipocyte (3T3-L1지방세포 및 제2형 당뇨모델($KK-A^{y}$)에서 잎새버섯(Grifola frondosa) 조다당체 추출물의 항당뇨 효과)

  • Park, Kum-Ju;Oh, Young-Joo;Lee, Sang-Yun;Kim, Hyun-Su;Ha, Hyo-Cheol
    • Korean Journal of Food Science and Technology
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    • v.39 no.3
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    • pp.330-335
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    • 2007
  • This study was performed to investigate the anti-diabetic mechanism of crude polysaccharides isolated from the fruiting bodies of Grifola frondosa. We treated 3T3-L1 adipocyte cells to observe whether the crude polysaccharides isolated from Grifola frondosa would stimulate insulin sensitivity. Significant insulin sensitizing activity was observed in the 3T3-L1 adipocytes, and giving the crude polysaccharide of Grifola frondosa with 1 nM of insulin caused glucose uptake to increase to a similar level as giving 50 nM of insulin alone. To confirm the mechanism for the anti-diabetic effect of the crude polysaccharides, we performed further examinations within $KK-A^{y}$ mice, an animal model of type 2 diabetes. The crude polysaccharides reduced blood glucose levels in the $KK-A^{y}$ mice for 2 weeks after feeding, and also significantly lowered plasma insulin levels. These results suggest that the anti-diabetic mechanism of the crude polysaccharide of Grifola frondosa is related to the enhancement of insulin sensitivity.

A Study on Development of New Products by Old Chicken Meat (노폐계(老廢鷄)를 이용(利用)한 육제품(肉製品) 개발(開發)에 관한 연구(硏究))

  • Han, Sung Wook;Lee, Kyu Seung;Chang, Kyu Sup;Jeon, Chang Kie
    • Korean Journal of Agricultural Science
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    • v.7 no.2
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    • pp.87-102
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    • 1980
  • In order to investigate the utilization probability of two years old laying hen for W.L. and R.I.R. breeds, carcass weight and percentage were examined and dried old chicken meat products were manufactured for experiments. The results obtained are as follows. 1. Average living body weight were 1,635.40g for the W.L. breeds and 2,289.29g for the R.I.R. breeds and percentage carcass and lean meat for the W.L. were 58.73% and 43.95%, for the R.I.R. 60.34%, 41.98%, respectively. 2. In constitution percentage of carcass on different parts for W.L. and R.I.R. breeds, head were 4.13% and 3.94%, wing 9.97% and 8.62%, breast 32.54% and 20.94%, back 11.35% and 9.75%, thigh 30.75% and 31.34%, hypordermic fat 11.37% and 17.34%, respectively. 3. In constitution percentage of lean meat on different parts for W.L. and R.I.R. breeds, head were 4.03% and 3.95%, wing 9.47% and 9.79%, breast 39.37% and 38.14%, back 11.24% and 9.40%, thigh 36.16% and 38.74%, respectively. 4. In chemical composition of old chicken meat for W.L. breed, moisture was 68.18%, crude protein 22.80%, crude fat 2.70%, extract 5.15% and crude ash 1.18% and for R.I.R. breed, moisture was 68.04%, crude protein 22.18%, crude fat 3.13%, extract 5.45% and crude ash 1.21%. 5. Weight loss in steaming for W.L. at $121^{\circ}C$ for 30min., 60min., and 90min. were 54.91, 56.43 and 58.42%, respectively, and for R.I.R. were 45.23, 47.68 and 49.68%, respectively. 6. The yield of old chicken meat product per a hen were 253.01g for W.L. and 368.64g for R.I.R., the ratio for fresh meat weight and for carcass weight were 35.47% and 26.34% for W.L. breed and 38.25 and 26.83% for R.I.R. breed. 7. In chemical composition of old chicken meat product for W.L., moisture was 16.69%, crude protein 66.16%, crude fat 12.81%, crude ash 4.35%, and R.I.R., moisture 16.11%, crude protein 65.95%, crude fat 13.78% and crude ash 4.57%. 8. To investigate the physical properties which was main factor affecting the product quality, tensile strength, tear strength and elongation rate were measured. The adhesive force of the product made under pressure of $70kg/cm^2$ was similar to those of chipo which was the control product. 9. When measured the color of each protein product, lightness of the product pressed at $70kg/cm^2$ was better than that at $35kg/cm^2$, and the lightness of breast muscle product at $70kg/cm^2$ and chipo was not significant as 16.7% and 16.4%, respectively. Dominant wavelength of product pressed at $70kg/cm^2$ was very similar to chipo which was yellowish orange. 10. In the results of sensory evaluation test containing taste, color, chewing texture and oder of the meat product, when index of chipo as control product was 100, index of breast meat product was higher than that as 118.4, but miscellaneous product was 99.7 and thigh product was 96.2. 11. Summing up the results written above, the meat product utilizing two years old laying hen was compared favorably with its similar food such as chipo on the point of nutrition and physical properties as high protein food, therefore, it was thought that industrialization must be highly appropriate.

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The Diagnostic Value of Isocapnic Hyperventilation of Cold Air in Adults with Suspected Asthma (기관지 천식을 의심하는 성인환자에서 등탄산 찬공기 과호흡의 진단적 유용성)

  • Cho, Jae-Hwa;Ryu, Jeong-Seon;Lee, Ji-Young;Kwak, Seung-Min;Lee, Hong-Lyeol;Cho, Chul-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.3
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    • pp.232-239
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    • 2001
  • Background : Asthmatic patients frequently suffer cold-weather-associated respiratory symptoms. The sensitivity, specificity, accuracy and diagnostic value of isocapnic hyperventilation of cold air(IHCA) using a multistep method, was investigated in patients suspected to have asthma. Method : One hundred and 29 adult patients who had an IHCA performed between july 1999 and December 2000, had an methacholine bronchoprovocation test because of a clinical suspicion of asthma. Results : According to strict criteria, 50 were defined as asthmatics and 79 as symptomatic nonasthmatics. There were no differences in age, sex and smoking state between the asthmatic and symptomatic nonasthmatic groups. There was a significant decrease in the percentage reduction in the forced expiratory volume in 1 second($FEV_1$) after the IHCA between the asthmatics($-10.0{\pm}6.8%$) and the symptomatic nonasthmatics($-2.3{\pm}2.5%)$. The factors associated with a reactivity to IHCA were $FEV_1$/FVC, $FEF_{25-75}$%/FVC and $FEV_1$(% of predicted). The accuracy was highest using a 7% fall in $FEV_1$ ; the sensitivity was 76% and the specificity 96%. Conclusion : IHCA is a specific, although not a sensitive, test for diagnosing asthma in adult patients. Furthermore, the diagnostic cut-off value of the different methods of IHCA need to be determined.

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Oestrus Induction, Plasma Steroid Hormone Profiles and Fertility Response after CIDR and eCG Treatment in Acyclic Sahiwal Cows

  • Singh, Harpreet;Luthra, R.A.;Khar, S.K.;Nanda, Trilok
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.11
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    • pp.1566-1573
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    • 2006
  • The study was conducted on 30 true acyclic Sahiwal cows (15 cows, ${\geq}90$ days postpartum; 15 postpubertal heifers, ${\geq}30$ months of age) and a similar 20 untreated controls (10 cows, 10 heifers). An 'Eazi' breed Controlled Internal Drug Release (CIDR) device (containing 1.38 g progesterone) was inserted intravaginally for 7 days (days 0 to 7) followed by 500 IU eCG i.m. at CIDR removal in all the treated animals. Heifers also received 5 mg oestradiol valerate i.m at CIDR insertion. The reproductive performance of these animals was recorded in terms of oestrus induction response, conception and pregnancy rates. Plasma progesterone ($P_4$) and oestradiol-$17{\beta}$ ($E_2$) profiles of 4 representative animals from each treatment group before, during and after CIDR treatment were also monitored. An oestrus induction response of 100% was observed in treated cows and heifers. The majority of cows (53.3%) and heifers (60%) were induced to oestrus within 24-36 and 36-48 h, respectively after CIDR withdrawal; with mean intervals of $44{\pm}3.18$ and $48{\pm}2.35h$, respectively. The conception rate at induced oestrus was higher in cows (40%) than heifers (20%). The final pregnancy rates after 2 subsequent oestruses were 80 and 60% in cows and heifers, respectively (overall 70% for all treated animals). In comparison, only 10% of control animals (2 cows only, 2/20) showed oestrus and become pregnant (10%) during theentire study period. The pretreatment (day 0) mean plasma P4 levels were statistically (p>0.05) similar in cows and heifers ($0.40{\pm}0.04$ and $0.49{\pm}0.11ng/ml$, respectively). The peak $P_4$ levels were observed on day 1 in cows ($13.94{\pm}1.41ng/ml$) and day 2 in heifers ($19.15{\pm}3.30ng/ml$) with a progressive decline up to the day of CIDR withdrawal ($3.35{\pm}0.92$ and $8.79{\pm}1.71ng/ml$, respectively). Mean $P_4$ levels on day 9 and 10 in cows and heifers did not differ significantly from their respective day 0 values and the lowest values were recorded on day 10 both in cows and heifers ($0.13{\pm}0.03$ and $0.14{\pm}0.02ng/ml$, respectively). Wide variations in individual pretreatment $E_2$ levels were observed both in the cows (range = 4-26, mean = $13.00{\pm}4.65pg/ml$) and heifers (range = 10-14, mean = $11.50{\pm}0.96pg/ml$). Thereafter also, $E_2$ levels in cows showed variation and reached a peak level ($53.50{\pm}2.99pg/ml$) on day 8. In heifers, peak mean $E_2$ level ($111.25{\pm}39.81pg/ml$) was recorded on day 1, followed by a non-significant decline on day 2, a significant fall on day 6 and a non-significant increase on day 9 and 10. However, mean $E_2$ levels on days 7 (p<0.05), 8 and 9 (p<0.01) were significantly higher in cows compared to heifers. The post-CIDR withdrawal mean highest $P_4$ and lowest $E_2$ levels coincided with the period when the majority of animals were induced to oestrus. CIDR and eCG treatment resulted in effective induction of oestrus with satisfactory pregnancy rates in true acyclic Sahiwal cows and heifers.

Effect of 5-aza-2'-deoxycytidine on Cell Proliferation of Non-small Cell Lung Cancer Cell Line A549 Cells and Expression of the TFPI-2 Gene

  • Dong, Yong-Qiang;Liang, Jiang-Shui;Zhu, Shui-Bo;Zhang, Xiao-Ming;Ji, Tao;Xu, Jia-Hang;Yin, Gui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4421-4426
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    • 2013
  • Objective: The present study employed 5-aza-2'-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer (NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. Methods: Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR, a specific demethylating agent, for 24, 48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM) to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), real time polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 gene methylation status, mRNA expression and protein expression. Results: MTT assay showed that the growth of A549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group (0 ${\mu}mol/L$ 5-Aza-CdR). After treatment with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h, FCM showed their proportion in G0/G1 was $69.7{\pm}0.99%$, $76.1{\pm}0.83%$, $83.8{\pm}0.35%$, $95.5{\pm}0.55%$ respectively (P<0.05), and the proportion in S was $29.8{\pm}0.43%$, $23.7{\pm}0.96%$, $15.7{\pm}0.75%$, $1.73{\pm}0.45%$, respectively (P<0.05), suggesting 5-Aza-CdR treatment induced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 gene was detected in control group (0 ${\mu}mol/L$ 5-Aza-CdR), and demethylation appeared after treatment with 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were $1{\pm}0$, $1.49{\pm}0.14$, $1.86{\pm}0.09$ and $5.80{\pm}0.15$ (P<0.05) respectively. Western blotting analysis showed the relative expression levels of TFPI-2 protein were $0.12{\pm}0.01$, $0.23{\pm}0.02$, $0.31{\pm}0.02$, $0.62{\pm}0.03$ (P<0.05). TFPI-2 protein expression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration. Conclusions: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expression in the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation of TFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinical treatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be one molecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR.

A Study on the Continuing Education of Dental Technicians (치과기공사의 보수교육에 관한 연구(I) -보수교육 실태와 인식을 중심으로 -)

  • Moon, Je-Hyuk
    • Journal of Technologic Dentistry
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    • v.22 no.1
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    • pp.179-198
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    • 2000
  • Since dental prosthesis is made possible only when dental technicians give themselves to the study of knowledge and the acquisition of updated skills, continuing education is of great importance in that it makes up for the efforts of dental technicians. Accordingly, continuing education relates to a system designed to contribute to the enhancement of the talents of dental technicians and the dental health of the nation. Specialized knowledge and information may work as the best weapon to preserve their jbs. This is true of this modern society where no one can expecth to survive without acquiring knowledge and information constantly for work is getting more classified and more divirsifide. This paper is dedicated to take a look at the current condition of the continuing education of dental technicians and to come up with measure to make general evaluation and to improve continuing education. This research resorts to 609 questionnaires among 6433 copies save unfaithfully responded 34 copos with 6.431 dental technicians as the subjects enrolled in the Dental technician Association. The collected questionnaires consist of 365 dental technicians living in Seoul and of 244 ones, Which account for 11.8 percent of dental technicians enrolled in the association. Because dental technicians live more in local areas than Seoul, the generalization of this survey leaves something to be desired. I have come up with the following findings. 1. 6,431 dental technicians, or 36.3 percent of an total of 14,956 licensed dental technicians, were admitted as numbers of the Dental Tachnician Association as of October 31, 1999. In the '98 continuing education. 4,141 dental technicians among 4,711 dental technicians got relevant training, and in the '99 continuing education, 4,075 technicians, or 75.9 percent of 5,365 technicians got relevant training while 1,290 technicians or 24.2 percent, fail to get relevant training. 2. The survey has it that 38.1 percent of dental technicians are ignorant of the laws on continuing education, and that technicians staying in local communities(146 persons, or 61.6%) take more part in education than those living in the capital of Korea(159 persons, or 146%), and that the older they are, the more money they earn, the more carrer they have, the higher position they hold, the more part they take in education 3. According to the survey, those who have the experience of getting training more than three times account for 52 persons(16.8%) in Seoul and 47 persons(22.4%) in local districts(p<0.01). In terms of sanctions in relation to continuing education, 26 dental technicians(4.6%) say that they have ever gotten sanctions, and 533 dental technicians(95.4%) say that they haven't. And those who were absent from continuing education(72 technicians : 13.51%) didn't get any sanction. 4. In terms of the degree of understanding continuing education, local technicians(46.8% : 110 persons) have a higher understanding of continuing education than their countparts staying in Seoul(36.0% : 130). Continuing education is not the ultimate goal itself. It should be changed to motivate those who get education to be willing to take part in contunuing education, and to help dental technicians in a practical and specific way. And the branch societies should be developde to engage in more specialized and classified expert fields. Of course, the curriculum should be so selected that the conceptions of dental technicians may be reflected to the maximum extent, and the ultimate effores should be made to effect diversity in the ways of educational methods and to perfect the preparation of continuing education on the part of instructors. Regulations should be established in relation to continuing education with a veiew to enhancing the participation of continuing education and its effectiveness. The supervision of the Ministry of Health and Welfare is of great importance in this context. The regulation of continuing education is not administrative regulation, but the expression of national will to guarantee the medical service of the nation at highest level. Therefore, it is necessary that the Ministry of Health and Welfare should change their understanding of the needs for the continuing education of dental experts, and that the expertise of government employees in charge of continuing education should be expanded. It goes without saying that the government should suppory continuing education in a financial way so as to supply the person in charge of public welfare and control the quality of national medicine.

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Effects of Organic TMR with Whole Barley Silage on Feed Intake, Nutrient Digestibility and Blood Characteristics in Korean Black Goats (총체 보리사일리지를 첨가한 유기 TMR 급여가 흑염소의 사료섭취량, 영양소 소화율 및 혈액성상에 미치는 영향)

  • Kim, Kwang-Kook;HwangBo, Soon;Jo, Ik-Hwan
    • Korean Journal of Organic Agriculture
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    • v.15 no.4
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    • pp.413-424
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    • 2007
  • This trial was carried out to determine effects of TMR(Total Mixed Ration) in comparison to conventional diet on feed intake, digestibility, and nitrogen retention in Korean black goats. Twelve Korean black goats were allotted to treatments in four groups of three goats and the they were housed in separate metabolism cages for 21 days. Treatments included conventional diet(A: rice straw and commercial concentrates) as a control group and three TMR groups(B: rice straw and commercial TMR; C: 30% organic whole barley silage and rice straw with organic grain; D: 60% organic whole barley silage with organic grain). The results obtained are summarized as follows. Dry matter intake, fecal excreta, digestible dry matter, metabolic intake and feed intake of BW were significantly higher(p<0.05) compared with A, B, C treatment. The digestibility for most of nutrients except NFC was significantly higher(p<0.05) for D treatment than the others. On the other hand, the digestibility of NFC was higher for B treatment than for the others, even if it was not significantly different across treatments. Nitrogen intake was lower for D treatment, but the significant differences were not found across treatments. N retention rate was higher for B treatment with significant difference. For the blood composition, HDL cholesterol and Immunoglobulin G were significantly higher(p<0.05) for C, D treatment than the others. The results showed that, in comparison with A treatment(conventional diet) and B treatment(commercial TMR), dry matter intake, nutrient digestibility and N retention rate were not lower in C treatment(30% organic whole barley silage) and HDL cholesterol was increased after experiment. Therefore, it could be concluded that TMR with organic whole barley silage might contribute to the production of a high quality and safer meat in goat production.

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Assessing Productivity of Elementary School Lunch Foodservices in Daegu and Gyeongsangbuk-do Area (대구ㆍ경북지역 초등학교 급식소의 급식생산성 분석)

  • 박영숙
    • Korean journal of food and cookery science
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    • v.19 no.3
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    • pp.286-294
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    • 2003
  • The purpose of this study was to analyze the food service management practices and productivity in 49 elementary schools in the Daegu and Gyeongsangbuk-do areas. Survey questionnaires were used to obtain a variety of quantitative and qualitative information, including general food service management and productivity, on elementary school food service systems. Descriptive analysis, $\div$2-test, t-test and one-way ANOVA analysis were used as the statistical methods in this study. Eighteen elementary schools were located in urban areas, 13 in provincial areas and 18 in isolated areas. The average number of meals was 565.1, with a significant difference (p=0.001) between the areas. The average cost per a meal was 1151.0 Won, with a significant difference (p=0.001) between the areas. The productivity Index (meal/hour) was 13.5, with a significant difference (p=0.001) between the areas. There was a significant positive correlation of the productivity Index between the total number of meal, the number of employees, the total food cost, meals per employee and the employee's working period. There was a significant negative correlation between the productivity Index and the number of side dishes, the lost per meal, the labor cost per meal and the employee's job satisfaction degree index (JDI).

Dietary behaviors and nutritional status according to the bone mineral density status among adult female North Korean refugees in South Korea (한국에 거주하고 있는 북한이탈주민 여성의 골밀도에 따른 식생활과 영양상태)

  • Kim, Su-Hyeon;Lee, Soo-Kyung;Kim, Sin-Gon
    • Journal of Nutrition and Health
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    • v.52 no.5
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    • pp.449-464
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    • 2019
  • Purpose: North Koreans could be at higher risk for their bone health because of previous periods of severe famine and the continuing low availability of food. This study determined the bone mineral density (BMD) status and its relationship with dietary behaviors and nutrient intake of North Korean refugees (NKR) in South Korea (SK). Methods: This cross-sectional study analyzed 110 female NKR from a NORNS cohort of a non-probability sample of adult NKR in Seoul. BMD examined by DEXA was used to divide participants into the normal group (NG) and the non-normal group (NNG) according to the WHO guideline. A self-administered questionnaire included questions on age, the socioeconomic situation in North Korea (NK) and SK, the food security in NK and SK, and the health behaviors, dietary behaviors, and food frequency questionnaire administered in SK. A one-day 24-hr recall was conducted and the results were analyzed by using CanPro. SPSS was used to analyze whether BMD and related dietary behaviors and nutrient intakes differed according to the groups. Results: NG (62.7%) was significantly younger and had a lower abdominal obesity score than NNG (p < 0.001). While 14.5% of NG reported experiencing menopause, all of NNG reported experiencing menopause. The NG more frequently consumed the dairy group of foods (9.6 times a week) than did the NNG (4.8 times a week) after the statistics were adjusted for age (p < 0.007). The NG consumed significantly more animal protein and animal calcium than did the NNG (p = 0.01, p = 0.009, respectively). Calcium intake was low with 49.3% of NG, and 78.0% of the NNG reported consuming calcium lower than the estimated average requirement. Only calcium showed an index of nutrient quality lower than one in both groups. Conclusion: These results showed that NKR women and possibly all North Korean women are at high risk for bone health and they consumed low levels of bone-related nutrients, and this should be considered for the nutrition policy for NKR and North Korea.

The Effectiveness of Fiscal Policies for R&D Investment (R&D 투자 촉진을 위한 재정지원정책의 효과분석)

  • Song, Jong-Guk;Kim, Hyuk-Joon
    • Journal of Technology Innovation
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    • v.17 no.1
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    • pp.1-48
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    • 2009
  • Recently we have found some symptoms that R&D fiscal incentives might not work well what it has intended through the analysis of current statistics of firm's R&D data. Firstly, we found that the growth rate of R&D investment in private sector during the recent decade has been slowdown. The average of growth rate (real value) of R&D investment is 7.1% from 1998 to 2005, while it was 13.9% from 1980 to 1997. Secondly, the relative share of R&D investment of SME has been decreased to 21%('05) from 29%('01), even though the tax credit for SME has been more beneficial than large size firm, Thirdly, The R&D expenditure of large size firms (besides 3 leading firms) has not been increased since late of 1990s. We need to find some evidence whether fiscal incentives are effective in increasing firm's R&D investment. To analyse econometric model we use firm level unbalanced panel data for 4 years (from 2002 to 2005) derived from MOST database compiled from the annual survey, "Report on the Survey of Research and Development in Science and Technology". Also we use fixed effect model (Hausman test results accept fixed effect model with 1% of significant level) and estimate the model for all firms, large firms and SME respectively. We have following results from the analysis of econometric model. For large firm: i ) R&D investment responds elastically (1.20) to sales volume. ii) government R&D subsidy induces R&D investment (0.03) not so effectively. iii) Tax price elasticity is almost unity (-0.99). iv) For large firm tax incentive is more effective than R&D subsidy For SME: i ) Sales volume increase R&D investment of SME (0.043) not so effectively. ii ) government R&D subsidy is crowding out R&D investment of SME not seriously (-0.0079) iii) Tax price elasticity is very inelastic (-0.054) To compare with other studies, Koga(2003) has a similar result of tax price elasticity for Japanese firm (-1.0036), Hall((l992) has a unit tax price elasticity, Bloom et al. (2002) has $-0.354{\sim}-0.124$ in the short run. From the results of our analysis we recommend that government R&D subsidy has to focus on such an areas like basic research and public sector (defense, energy, health etc.) not overlapped private R&D sector. For SME government has to focus on establishing R&D infrastructure. To promote tax incentive policy, we need to strengthen the tax incentive scheme for large size firm's R&D investment. We recommend tax credit for large size film be extended to total volume of R&D investment.

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