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A Study of Microsatellite Instability in Primary Small Cell Lung Cancers by Microsatellite Analysis (원발성 소세포폐암에서 Microsatellite 분석을 이용한 Microsatellite 불안정화에 대한 연구)

  • Cho, Eun-Song;Chang, Joon;Park, Jae-Min;Shin, Dong-Hwan;Kim, Se-Hoon;Kim, Young-Sam;Chang, Yoon-Soo;Cho, Chul-Ho;Kwak, Seung-Min;Lee, Jun-Gu;Chung, Kyung-Young;Kim, Sung-Kyu;Lee, Won-Young;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.180-190
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    • 2000
  • Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

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Analysis of the Effects of Some Meteorological Factors on the Yield Components of Rice (수도 수량구성요소에 미치는 기상영향의 해석적 연구)

  • Seok-Hong Park
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.18
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    • pp.54-87
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    • 1975
  • The effects of various weather factors on yield components of rice, year variation of yield components within regions, and regional differences of yield components within year were investigated at three Crop Experiment Stations O.R.D., Suweon, Iri, Milyang, and at nine provincial Offices of Rural Development for eight years from 1966 to 1973 for the purpose of providing information required in improving cultural practices and predicting the yield level of rice. The experimental results analyzed by standard partial regression analysis are summarized as follows: 1. When rice was grown in ordinary seasonal culture the number of panicles greatly affected rice yield compared to other yield components. However, when rice was seeded in ordinary season and transplanted late, and transplanted in ordinary season in the northern area the ratio of ripening was closely related to the rice yield. 2. The number of panicles showed the greatest year variation when the Jinheung variety was grown in the northern area. The ripening ratio or 1, 000 grain weight also greatly varied due to years. However, the number of spikelets per unit area showed the greatest effects on yield of the Tongil variety. 2. Regional variation of yield components was classified into five groups; 1) Vegetation dependable type (V), 2) Partial vegetation dependable type (P), 3) Medium type (M), 4) Partial ripening dependable type (P.R), and 5) Ripening dependable type (R). In general, the number of kernel of rice in the southern area showed the greatest partial regression coefficient among yield components. However, in the mid-northern part of country the ripening ratio was one of the component!; affecting rice yield most. 4. A multivariate equation was obtained for both normal planting and late planting by log-transforming from the multiplication of each component of four yield components to additive fashion. It revealed that a more accurate yield could be estimated from the above equation in both cases of ordinary seasonal culture and late transplanting. 5. A highly positive correlation coefficient was obtained between the number of tillers from 20 days after transplanting and the number of panicles at each(tillering) stage 20 days after transplanting in normal planting and late planting methods. 6. A close relationship was found between the number of panicles and weather factors 21 to 30 days, after transplanting. 7. The average temperature 31 to 40 days after transplanting was greatly responsible for the maximum number of tillers while the number of duration of sunshine hours per day 11 to 30 days after transplantation was responsible for that character. The effect of water temperature was negligible. 8. No reasonable prediction for number of panicles was calculated from using either number of tillers or climatic factors. The number of panicles could early be estimated formulating a multiple equation using number of tillers 20 days after transplantation and maximum temperature, temperature range and duration of sunshine for the period of 20 days from 20 to 40 days after transplantation. 9. The effects of maximum temperature and day length 25 to 34 days before heading, on kernel number per panicle, were great in the mid-northern area. However, the minimum temperature and day length greatly affected the kernel number per panicle in the southern area. The maximum temperature had a negative relationship with the kernel number per panicle in the southern area. 10. The maximum temperature was highly responsible for an increased ripening ratio. On the other hand, the minimum temperature at pre-heading and early ripening stages showed an adverse effect on ripening ratio. 11. The 1, 000 grain weight was greatly affected by the maximum temperature during pre- or mid-ripening stage and was negatively associated with the minimum temperature over the entire ripening period.

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Characterization of Traits Related to Grain Shape in Korean Rice Varieties (국내 육성 벼 품종 입형 관련 특성 분석)

  • Lee, Chang-Min;Lee, Keon-Mi;Baek, Man-Kee;Kim, Woo-Jae;Suh, Jung-Pil;Jeong, Oh-Young;Cho, Young-Chan;Park, Hyun-Su;Kim, Suk-Man
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.65 no.3
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    • pp.199-213
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    • 2020
  • Grain size and shape are the two important components contributing to rice yield and quality. To analyze traits related to grain-shape, a total of 272 varieties derived from japonica, japonica black and Tongil-type rice accession in Korea were evaluated in this study. The traits, grain length (GL), grain width (GW), grain thickness (GT), length to width ratio (RLW), and 1000-grain weight (TGW) were measured and replicated 10 times. Genes (GW2, GS3, qGL3, qSW5, GS5, TGW6, GW7, and GW8) related to grain-shape were validated in the accessions using specific DNA marker sets. K-mean clustering of the accession based on phenotypic data revealed three groups: group 1 was classified by GW and GT and included most of japonica type, group 2 was classified by RLW and GL reached a medium size and possessed a half spindle-shaped type, and group 3 was classified by TGW, reached a long size and possessed a semi-round shape. In validation tests using the marker sets, both gw2 and tgw6 were validated in less than 1% of the tested accessions and two allelic types, qgl3 and gw8, were only verified in Tongil-type accessions. For GW8 and GW2, any different amplicons were not amplified in any japonica or Tongil-type accessions, respectively. In order to suggest the representative grain-shape gene combinations for each ecotype, the allelic combinations were evaluated by PCR analysis. Cj1 and 2 in japonica (Cj1-7), Cj_b1 and 2 in japonica-black (Cj_b1-3), and CT3 in Tongil-type (CT1-13) turned out to be the dominant combination in each ecotype, respectively. In addition, the results revealed that introgression of four genes (gw2, gs3, qSW5, and GS5) would expand the diversity of grain shape in Korean japonica varieties. The gene combinations information could be utilized practically to understand or enhance grain shape in japonica rice breeding program.

An Epidemiological Study on the Industrial Injuries among Metal Products Manufacturing Workers in Young-Dung-Po, Seoul (일부 금속 및 기계제품 제조업체 근로자들의 산업재해($1980{\sim}1981$)에 관한 조사)

  • Lee, Jung-Hee
    • Journal of Preventive Medicine and Public Health
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    • v.15 no.1
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    • pp.187-196
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    • 1982
  • The followings are the results of the study on industrial accidents occurred at 12 factories manufacturing metal products during the period of 2 years from January 1980 to December 1981 in the area of Yong-Dung-Po in Seoul. The results of the study are as follows: 1. The incidence rate of industrial injuries was 45.7 per 1,000 workers of the sample group and the rate of male (54.0) was three times higher than that of female (17.5). 2. In age groups, the highest rate was observed in the group of under 19 years old with 83.5, while the lowest in the group of 40s. 3. It was found that those who had short term of work experience produced a higher rate of injuries, particularly, the group of workers with less than 1 year of experience showed the highest rate of it as 48.1%. 4. In working time, the highest incidence rate occurred 3 and 7 hours after the beginning of their working showing the rate of 6.0 and 6.1 per 1,000 workers, respectively. 5. The highest incidence rate was observed on Monday as 8.4 per 1,000 workers, and it was 18.3% in aspect of the days of a week. 6. In aspect of the months of a year, the highest incidence was observed on July 1,000 workers and the next was on March as 4.8. These figures account for 11.8% of total occurrence in respective month. as 5. 4 per and 10.5% 7. In causes of injuries, the accident caused by power driven machinery showed the highest rate with 37.5%, the second was due to handling without machinery with 17.2%, and the third was due to falling objects with 14.2%, and striking against objects with 10.2%, and so on. 8. By parts of the body affected, the most injuries 84.3% of them occurred on both upper and lower extremities with the rate of 58.8% for the former and 25.5% for the latter. Fingers were most frequently injured with a rate of 40.3%. Comparing the sites of extremities affected, rate of injuries on the right side was 55.0% and 45.0% on the left side. 9. In the nature of injury, laceration and open wound were the highest with 34. 0%, the next was fracture and dislocation with 31. 9%, and sprain was the third with 8.1%. 10. On the duration of treatment, it lasted less than one month in 68.9% of the injured cases, of which 14.5% of the cases were recovered within 2 weeks, and 54.4% of them were treated more than 2 weeks. And the duration of the treatment tended to be prolonged in larger industries. 11. The ratio of insured accidents to uninsured accidents was 1 to 4.7.

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INFLUENCES OF DRY METHODS OF RETROCAVITY ON THE APICAL SEAL (치근단 역충전와동의 건조방법이 폐쇄성에 미치는 영향)

  • Lee, Jung-Tae;Kim, Sung-Kyo
    • Restorative Dentistry and Endodontics
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    • v.24 no.1
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    • pp.166-179
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    • 1999
  • Apical sealing is essential for the success of surgical endodontic treatment. Root-end cavity is apt to be contaminated with moisture or blood, and is not always easy to be dried completely. The purpose of this study was to evaluate the influence of dry methods of retrocavity on the apical seal in endodontic surgery. Apical seal was investigated through the evaluation of apical leakage and adaptation of filling material over the cavity wall. To investigate the influence of various dry methods on the apical leakage, 125 palatal roots of extracted human maxillary molar teeth were used. The clinical crown of each tooth was removed at 10 mm from the root apex using a slow-speed diamond saw and water spray. Root canals of the all the specimens were prepared with step-back technique and filled with gutta-percha by lateral condensation method. After removing of the coronal 2 mm of filling material, the access cavities were closed with Cavit$^{(R)}$. Two coats of nail polish were applied to the external surface of each root. Apical three millimeters of each root was resected perpendicular to the long axis of the root with a diamond saw. Class I retrograde cavities were prepared with ultrasonic instruments. Retrocavities were washed with physiologic saline solution and dried with various methods or contaminated with human blood. Retrocavities were filled either with IRM, Super EBA or composite resin. All the specimens were immersed in 2% methylene blue solution for 7 days in an incubator at $37^{\circ}C$. The teeth were dissolved in 14 ml of 35% nitric acid solution and the dye present within the root canal system was returned to solution. The leakage of dye was quantitatively measured via spectrophotometric method. The obtained data were analysed statistically using one-way ANOVA and Duncan's Multiple Range Test. To evaluate the influence of various dry methods on the adaptation of filling material over the cavity wall, 12 palatal roots of extracted human maxillary molar teeth were used. After all the roots were prepared and filled, and retrograde cavities were made and filled as above, roots were sectioned longitudinally. Filling-dentin interface of cut surfaces were examined by scanning electron microscope. The results were as follows: 1. Cavities dried with paper point or compressed air showed less leakage than those dried with cotton pellet in Super EBA filled cavity (p<0.05). However, there was no difference between paper point- and compressed air-dried cavities. 2. When cavities were dried with compressed air, dentin-bonded composite resin-filled cavities showed less apical leakage than IRM- or Super EBA-filled ones (p<0.05). 3. Regardless of the filling material, cavities contaminated with human blood showed significantly more apical leakage than those dried with compressed air after saline irrigation (p<0.05). 4. Outer half of the cavity showed larger dentin-filling interface gap than inner half did when cavities were filled with IRM or Super EBA. 5. In all the filling material groups, cavities contaminated with blood or dried with cotton pellets only showed larger defects at the base of the cavity than ones dried with paper points or compressed air.

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Multiple Daily Fractionated RT for Malignant Glioma (악성 성상세포종과 다형성 교아종 치료에 있어서 다분할 방사선 치료와 단순분할 방사선치료에 대한 성적비교)

  • Yang Kang Mo;Chang Hye Sook;Ahn Seoung Do;Choi Eun Kyung
    • Radiation Oncology Journal
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    • v.12 no.2
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    • pp.151-158
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    • 1994
  • Since Jan. 1992, authors have conducted a pilot study to treat malignant glioma with multiple daily fractionated(MDF) radiation therapy and this paper presents the outcome compared MDF to conventional factionated(CF) radiation therapy Between Sep. 1989 and Jan. 1993, forty three patients with high grade glioma of brain except brain stem glioma were treated: nineteen patients were treated with CF radiation therapy and 24 patients were treated with MDF radiation therapy. In CF radiation therapy, total dose was 6300cGy/35fx in 7 weeks, which 5040cGy was delivered to the initial target volume and 1260cGy to reduced target volume. And in MDF radiation therapy, total dose was 6400cGy/40fx in 4 weeks, which 3200cGy was delivered to the initial target volume as 160cGy 2 times daily 6hr apart. All patients had histologically confirmed anaplastic astrocytoma(AA) of glioblastoma multiforme (GBM) with stereotactic biopsy or craniotomy for subtotal or gross tumor resection. The range of follow-up was 7 months to 4 years with a median follow-up of 9 months. The Median survival from surgery was 9 months for all patients. The median survival was 9 months and 10 months for MDF group and CF group and 10 months and 9.5 months for glioblastoma multiforme and anaplastic astrocytoma, respectively. In 36 patients with follow-up CT scan or MRI scan, disease status was evaluated according to treatment groups, Four patients(GBM:3, AA:1) of 21 patients in MDF group, were alive with no evidence of disease, while none of patient was alive with no evidence of disease in CF group. The progression of disease had occurred in 20 patients, 11 patients and 9 patients in MDF group and CF group, respectively All of these patients showed in-field progression of disease, Four of 11 patients($27\%$) in MDF group showed the new leasion outside of the treatment field, while 5 of 9 patients($56\%$) in CF group. In our study the prognosis was not influenced by age, KPS, grade, extent of surgery and different fractional scheduled radiation therapy. Authors concluded that MDF regimen was well tolerated and shortened the treatment period from 7 weeks to 4 weeks without compromising results. We believe that further follow-up is needed to assess the role of MDF.

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Increased Peripheral NK Cell Fraction and Their Cytolytic activity in Patients with History of Recurrent Spontaneous Abortion (말초혈액 자연살해세포 분획 및 세포용해 활성도 분석을 통한 습관성 유산 위험군의 진단적 유용성에 관한 연구)

  • Choi, Ji-Young;Hwang, Su-Jin;Han, Ae-Ra;Yoo, Ji-Hee;Park, Dong-Wook;Park, Chan-Woo;Kim, Hye-Ok;Cha, Sun-Hwa;Kim, Jin-Young;Song, In-Ok;Koong, Mi-Kyoung;Kang, In-Soo;Yang, Kwang-Moon
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.2
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    • pp.115-124
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    • 2010
  • Objective: To testify whether the increased peripheral blood natural killer (pbNK) cells fraction and their cytolytic activity could coincide with patient's history of recurrent spontaneous abortion (RSA) and to evaluate these factors are can be valuable diagnostic markers in RSA. Methods: Women with a history of RSA comprised the patient group (n=35). Normal fertile women, who were experienced at least one healthy term birth without history of infertility or recurrent miscarriage, were included as the healthy control group (n=15). The pbNK cells of $CD3^-/CD56^+/CD16^+$ and their cytolytic activities against K562 cells were measured by flow cytometry and the values were compared between study and control groups. Results: Proportions of pbNK cells among peripheral blood monocytes (PBMC) ($14.2{\pm}5.2$ vs. $9.4{\pm}3.7%$, p=0.002, 95% confidence interval [CI], 1.8 to 7.8) was significantly higher in the patient group. The odds ratio of having RSA history was increased as 8.4 folds (59% of sensitivity, 80% of specificity, and 95% CI: 2.0 to 35.8) in patients who showed pbNK cells fraction above 12.1% which was determined as cut-off value by using ROC curve analysis. The cytolytic activities of pbNK cells which measured by three different ratio of effecter pbNK cells to target K562 cells and calculated by the percent of cytolytic K562 cells, were significantly higher in study group than that of control group (in 50:1 ratio, $48.3{\pm}19.0$ vs. $31.3{\pm}11.9%$, p=0.002; in 25:1 ratio, $37.0{\pm}18.1$ vs. $20.2{\pm}9.2%$, p<0.001; in 12.5:1 ratio, $23.5{\pm}12.7$ vs. $12.4{\pm}7.3%$, p=0.001). With the cut-off values of cytolytic activity of pbNK cells as 43.1% (50:1), 26.9% (25:1), and 17.4% (12.5:1) each, the risk of having RSA history was increased by 10.0, 11.4, and 15.0 folds in patients who had increased in each effector of pbNK to target of K562 cells ratio. Conclusion: The analysis of pbNK cells fraction and their cytolytic activity can be valuable diagnostic markers for RSA. We are going to planning the large scaled studies which include the data of obstetric outcomes in subsequent pregnancies to clarify our results of this study.

A Time Series Graph based Convolutional Neural Network Model for Effective Input Variable Pattern Learning : Application to the Prediction of Stock Market (효과적인 입력변수 패턴 학습을 위한 시계열 그래프 기반 합성곱 신경망 모형: 주식시장 예측에의 응용)

  • Lee, Mo-Se;Ahn, Hyunchul
    • Journal of Intelligence and Information Systems
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    • v.24 no.1
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    • pp.167-181
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    • 2018
  • Over the past decade, deep learning has been in spotlight among various machine learning algorithms. In particular, CNN(Convolutional Neural Network), which is known as the effective solution for recognizing and classifying images or voices, has been popularly applied to classification and prediction problems. In this study, we investigate the way to apply CNN in business problem solving. Specifically, this study propose to apply CNN to stock market prediction, one of the most challenging tasks in the machine learning research. As mentioned, CNN has strength in interpreting images. Thus, the model proposed in this study adopts CNN as the binary classifier that predicts stock market direction (upward or downward) by using time series graphs as its inputs. That is, our proposal is to build a machine learning algorithm that mimics an experts called 'technical analysts' who examine the graph of past price movement, and predict future financial price movements. Our proposed model named 'CNN-FG(Convolutional Neural Network using Fluctuation Graph)' consists of five steps. In the first step, it divides the dataset into the intervals of 5 days. And then, it creates time series graphs for the divided dataset in step 2. The size of the image in which the graph is drawn is $40(pixels){\times}40(pixels)$, and the graph of each independent variable was drawn using different colors. In step 3, the model converts the images into the matrices. Each image is converted into the combination of three matrices in order to express the value of the color using R(red), G(green), and B(blue) scale. In the next step, it splits the dataset of the graph images into training and validation datasets. We used 80% of the total dataset as the training dataset, and the remaining 20% as the validation dataset. And then, CNN classifiers are trained using the images of training dataset in the final step. Regarding the parameters of CNN-FG, we adopted two convolution filters ($5{\times}5{\times}6$ and $5{\times}5{\times}9$) in the convolution layer. In the pooling layer, $2{\times}2$ max pooling filter was used. The numbers of the nodes in two hidden layers were set to, respectively, 900 and 32, and the number of the nodes in the output layer was set to 2(one is for the prediction of upward trend, and the other one is for downward trend). Activation functions for the convolution layer and the hidden layer were set to ReLU(Rectified Linear Unit), and one for the output layer set to Softmax function. To validate our model - CNN-FG, we applied it to the prediction of KOSPI200 for 2,026 days in eight years (from 2009 to 2016). To match the proportions of the two groups in the independent variable (i.e. tomorrow's stock market movement), we selected 1,950 samples by applying random sampling. Finally, we built the training dataset using 80% of the total dataset (1,560 samples), and the validation dataset using 20% (390 samples). The dependent variables of the experimental dataset included twelve technical indicators popularly been used in the previous studies. They include Stochastic %K, Stochastic %D, Momentum, ROC(rate of change), LW %R(Larry William's %R), A/D oscillator(accumulation/distribution oscillator), OSCP(price oscillator), CCI(commodity channel index), and so on. To confirm the superiority of CNN-FG, we compared its prediction accuracy with the ones of other classification models. Experimental results showed that CNN-FG outperforms LOGIT(logistic regression), ANN(artificial neural network), and SVM(support vector machine) with the statistical significance. These empirical results imply that converting time series business data into graphs and building CNN-based classification models using these graphs can be effective from the perspective of prediction accuracy. Thus, this paper sheds a light on how to apply deep learning techniques to the domain of business problem solving.

Prevalence of Metabolic Syndrome and Assessment of Food·Nutrient Intakes among Adult Visitors of a Public Health Center in Korea (일부 보건소 내원자의 대사증후군 발현과 식품 및 영양소 섭취 실태)

  • Jeong, Won-Hoon;Jin, Bok-Hee;Hwang, Eun-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.2
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    • pp.205-212
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    • 2012
  • This study was performed to investigate the prevalence of metabolic syndrome (MS) and assess nutrient intake levels for the purpose of improving MS risk factors. The participants in this study were 512 adults consisting of 271 men and 241 women aged 30 and over, who visited a public health center for a medical check up. The diagnosis of MS subjects was adapted from the NCEP-ATPIII guidelines and the WHO Asia-Pacific Area criteria for obesity. The MS group was defined as subjects displaying three or more risk factors, and the non MS group was defined as those displaying two or less risk factors. A dietary survey was conducted using the 24-hour recall method. The number of subjects displaying MS syndrome factors was 158 (30.9%), broken down into, 89 men and 69 women. Regarding risk factors in the MS group, the prevalence of waist circumference was 40.5%, hypertension 34.2%, hyperglycemia 31.0%, low HDL-cholesterol 24.7%, and hypertriglycemia 19.6%. BMI, sistolic blood pressure, blood glocose, blood triglyceride, and blood HCL-cholesterol of the MS group were significantly higher compared to the non MS group. Male subjects in the MS group reported high intakes of cereals, sugar, fruits, meat and poultry, oil and fats, and beverages and total food intake was significantly higher compared to the non MS group. Women in the MS group reported high intakes of meat and poultry, milk and dairy products, beverages, and seasonings, and total food intake was higher compared to the non MS group. Dietary diversity score (DDS) was 3.82~4.04, which was not significant among the groups. In men, dietary variety score (DVS) was 16.3 in the MS group and 19.4 in the non MS group, whereas in women, the DVS was 15.2 in the non MS group and 17.0 in the MS group. In GMVDF pattern, 11111 pattern was 30.7%, followed by 01111 for men and 11101 for women. Calorie, fat, and cholesterol intakes in men as well as, calorie, fat, and folate intakes in women in the MS group were higher compared to the non MS group. Intakes of protein, P, Fe, Na, vitamin $B_1$, vitamin $B_2$, niacin, vitamin E, and Zn were higher than the KDRIs. On the other hand, intakes of Ca, K, fiber, vitamin $B_2$, and vitamin C were below the KDRIs. Intakes of lipids, animal food, Na, and cholesterol in the MS group were higher compared to the non MS group, whereas intake of dietary fiber was lower. Our results indicate that continuous, systematic nutritional education program must implemented to reduce the risk factors associated with MS.

The Effect of Dexamethasone on Airway Goblet Cell Hyperplasia and Inflammation in $TiO_2$-Treated Sprague-Dawley Rats ($TiO_2$로 처치된 백서에서 기도내 배상세포 증식과 염증에 대한 Dexamethasone의 효과)

  • Lim, Gune-Il;Kim, Do-Jin;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.1
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    • pp.37-48
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    • 2000
  • Backgrounds : The pathophysiology of chronic airflow obstruction, such as bronchial asthma, is characterized by mucus hypersecretion, goblet cell hyperplasia(GCH), smooth muscle hypertrophy, and inflammatory cells infiltration. In fatal asthma patients, one distinct findings is mucus hypersecretion due to GCH. However, the mechanisms of GCH in these hypersecretory diseases remain still unknown. In this study, a rat model was rapidly induced with GCH by instillation of $TiO_2$, intratracheally. We intend to confirm GCH and association of concomitant inflammatory cells infiltration and to observe the effect of potent antiinflammatory agent, that is dexamethasone, on GCH with inflammatory cells. Methods : Twenty-one 8-weeks-old male Sprague-Dawley rats were divided into three groups. Endotoxinfree water was instilled intratracheally in group 1(control) ; $TiO_2$, was instilled in the group 2 ; and dexamethasone was injected intraperitoneally to group 3 before $TiO_2$ instillation. After 120 hours, all rats were sacrificed, and trachea, bronchi, and lungs were resected respectively. These tissues were made as paraffin blocks and stained as PAS for goblet cells and Luna stain for eosinophils. We calculated the ratio of goblet cell to respiratory epithelium and number of infiltrated eosinophils from each tissue. Results : (1) Fraction of goblet cells was significantly increased in group 2 than in group 1 in the trachea and in the main bronchus. (10.19$\pm$11.33% vs 4.09$\pm$8.28%, p<0.01 and 34.09$\pm$23.91% vs 3.61$\pm$4.84%, p<0.01, respectively). (2) Eosinophils were significantly increased in the airway of group 2 than that of group 1. (5.43$\pm$3.84% vs 0.17$\pm$0.47 in trachea and 47.71$\pm$16.91 vs 2.71$\pm$1.96 in main bronchi). (3) There was a positive correlation between goblet cells and eosinophils(r=0.719, p=0.001). (4) There was significant difference in the decrease of goblet cells after dexamethasone injection between group 2 and group 3 (p<0.01). Also, infiltration of eosinophils was suppressed by dexamethasone. Conclusion : We made an animal model of $TiO_2$-induced goblet cell hyperplasia. GCH was observed mainly in the main bronchi with concomitant eosinophilic infiltration. Both goblet cell hyperplasia and eosinophilic infiltration were suppressed by dexamethasone. This animal model may serve as a useful tool in understanding of the mechanism of GCH in chronic airway diseases.

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