• YAKHAK HOEJI
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• v.52 no.5
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• Journal of Acupuncture Research
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• v.32 no.1
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• pp.53-66
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• 2015

Objectives : This study was designed to investigate effects of Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ on monosodium iodoacetate-induced osteoarthritic rats. Methods : Twenty rats were divided into four groups consisting of 5 rats: rats receiving no injection(normal), rats injected with monosodium Iodoacetate(MIA, control), rats injected with MIA and normal saline(N-S), and rats injected with MIA and Curculiginis Rhizoma (CRPA). N-S and CRPA were administered once a day at $ST_{36}$ during 21 days. After that we examined the weight-bearing ability of hind paws, liver and kidney function, immunocell, cytokines, proteins, and gene expression of cytokines. Injury of synovial tissue was measured by H & E, Safranin O immunofluorescence. Results : The weight-bearing ability of the hind paws, Serum TNF-${\alpha}$, IL-$1{\beta}$, IL-6, PGE2, LTB4, DPD, Osteocalcin, Protein COX-2 of CRPA decreased significantly. Protein Arachidonate 5 lipoxygenase of CRPA was decreased, but not significantly. Expression of gene COX-2, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, NOS2 of CRPA decreased. In histological observations, CRPA was improved, compared with other control groups. Conclusions : It can be suggested that Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ has anti-inflammatory and pain relief effects on monosodium iodoacetate-induced osteoarthritic rats.

• Journal of Information Technology and Architecture
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• v.9 no.3
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• pp.275-285
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• 2012

DIFs (Data Interchange Formats) are needed to enhance interoperability of physically distributed organizations in SBA (Simulation Based Acquisition) process. DIFs play a role as a template of DPDs (Distributed Product Descriptions) and provide capability to use information directly without data format interchange process by allowing access to DPDs, which include various information and M&S (Modeling & Simulation) resources. This characteristic is essential for interoperability in ICE (Integrated Collaborative Environment) based SBA. This paper proposes a framework for the DIF and outputs from each phase of acquisition process for configuration data related to design and manufacturing in SBA process - Conceptual Data Model, Logical Data Model, Physical Data Model and Physical DIF based on XML. Finally, we propose the DIF model architecture and demonstrate the implementation of DIF example based on it.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.4
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• pp.37-46
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• 2019

Objectives The purpose of this study is to confirm the efficacy and safety of the treatment of with fermented oyster extract on height growth in children with short stature. Methods A total of 100 people, between 6 and 11 years old, will be participated in a randomized, double-blind, and placebo-controlled human study. The fermented oyster group will take 500 mg of fermented oyster extract once a day for 24 weeks. The placebo group will take 3400 mg of fructooligosaccharide as placebo once a day for 24 weeks. The outcomes of the intervention will be measured at the baseline, 6 week, 12 week, 18 week, and 24 week. The primary outcome is the changes in height from the baseline. The secondary outcomes are growth rate, height SDS, bone age, GH, IGF-1, IGFBP-3, osteocalcin, BALP, DPD, and LH. Results This trial was approved by the institutional review board of Pusan National University Korean Medicine Hospital (registry number: PNUKHIRB-2019002). Recruitment of the research participants will be opened from May 2019 till December 2019. Conclusions This study will provide clinical information to determine the efficacy and safety of the treatment with fermented oyster extract on height growth in children with short stature.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.23-27
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• 2018

Purpose The introduction of bone scan has been reported as a useful tool in the diagnosis, treatment, and treatment response of skeletal disease. The purpose of this study is to improve the anatomical information and tolerance of the bone by combining bone scan and pelvic X-ray without additional radiation exposure. Materials and Methods From November 2015 to August 2016, 236 patients(64 men and 172 women, average age $50.96{\pm}15.39years$) take Bone scan and Pelvis AP(Anteroposterior) X-ray scan at the National Cancer Center. The scan equipment was a gamma camera, Symbia Ecam (SIEMENS, Germany), and a digital x-ray, DRS-800 (Listem, Korea). Osirix version 3.8.1 (Osirix, USA) and Stata/SE version 14.0 (StataCorp, USA) were used for image combination and analysis. The patient was intravenously injected with $^{99m}Tc-DPD$ (740 MBq), and the scan was performed 2 to 4 hours later. Gamma camera image acquisition were Matrix size $256{\times}1024$, Zoom 1.00, and scan speed 17 cm/min. The digital X-ray was made with a collimator size of $14^{{\prime}{\prime}}{\times}17^{{\prime}{\prime}}$, 77 kVp (60 to 97 kVp) and an average of 30 mAs (20 to 48). ASIS and pubic symphysis Select virtual points then Combine three virtual points and pelvic contour lines. The acquired images were evaluated by three radiologists who worked for more than 5 years in the nuclear medicine department. Results Of the total 236 patients, 216 (91.53%) were matched. The median and range (min~max) of the age were 67 (46~81) years old in the unmatched group and 52 (22~87) years old in the matched group, The Wilcoxon rank-sum test was performed to determine whether age was different between the two groups. As a result, the age difference between the two groups was statistically significant at p < 0.0001. Of the 64 men, 60 (93.75%) were match and of the 172 women, 156 (93.75%) were match. There was no statistically significant difference according to gender(p = 0.4542). Of the 54 patients without pelvic lesions, 54 (100.00%) were match, and 162 (89.01%) of 182 patients with pelvic lesions were match. There was a statistically significant difference according to the presence of pelvic lesions. Conclusion There are many variables in the combination of bone scan and pelvic X-ray imaging, and the patient's age and pelvic lesion may have some effect on the image combination. This study is expected to be useful for the diagnosis of pelvic osteosarcoma of children without radiation exposure. It is expected that this combination of images will help to develop the nuclear medicine image.

• Journal of Nutrition and Health
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• v.40 no.8
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• pp.719-727
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• 2007

To elucidate the relationship among the levels of nutrients intake, bone mineral density(BMD) and the urinary biochemical markers of bone metabolism, this survey is conducted with 225 postmenopausal women over 50 years of age. The urinary biochemical markers including deoxypyridinoline(DPD) and Ca excretion were measured. Bone mineral densities of lumbar spine(L2-L4), femoral neck, ward's triangle and trochanter were measured with dual-energy X-ray absorptiometry and the nutrient intake data obtained by 24 hr recall method. Mean age of all subjects was 64.8 years old, and the BMDs of the subjects were $0.86g/cm^2$(lumbar spine), $0.60g/cm^2$(femoral neck), $0.49g/cm^2$(trochanter), and $0.41g/cm^2$(ward's triangle). The results were compared among 3 groups with different nutrient intake levels classified by the percentage of Dietary Reference Intakes(DRIs) for Koreans as follows: low < 75% DRIs, 75% DRI $\leq$ adequate < 125% DRIs, high $\geq$ 125% DRIs. Bone mineral density of adequate protein intake group was significantly higher than those of low and high protein intake groups(p<0.05). Urinary DPD excretion was lowest in protein and calcium adequate intake groups(p<0.05, p<0.05), respectively. In relation to urinary Ca excretion, it is revealed to be considerably lower in the groups taking protein and vitamin C adequate intake(p<0.05, p<0.05). The percent DRI of protein and calcium were positively correlated with the BMD of the femoral neck after adjusted age(p<0.05, p<0.05). These results showed that there are probably some relationships between nutrient intake levels and urinary biochemical markers. For postmenopausal women with adequate nutrition expecially protein, calcium and vitamin C, has an important role to postpone bone resorption and to prevent the decrease of bone density.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.2
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• pp.182-187
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• 2013

This study was conducted to examine the effect of calcium extracted from salted anchovy (Engraulis japonicus) on the calcium metabolism of rats. Sprague-Dawley male rats were fed low-calcium diets (0.15%) for 2 weeks after the adjustment period. Rats were divided into five groups and were fed experimental diet for four weeks. Experimental diets were low calcium (LC, 0.15% $CaCO_3$), 0.5% $CaCO_3$ (CC), seaweed calcium (SC), calcium lactate (LC), anchovy calcium (AC). The low-calcium diet group (LC) showed the lowest weight gain and had no differences among the groups with adequate calcium intake. Calcium retention was lowest in the LC group and higher in the CL, SC, AC groups than in SC groups. Serum alkaline phosphatase (ALP) level was highest in LC group, and significantly low in the CC and AC groups (p<0.05). Parathyroid hormone and osteocalcin levels showed no differences among experimental groups. The urine deoxypyridinoline (DPD) level was lower in AC and CC groups compared to the LC group (p<0.05). The dry weight of the femur showed no significant differences among normal calcium groups. The bone mineral density of the femur in AC and CC group were significantly higher than the LC group (p<0.05). From these results, calcium extracted from salted anchovy can be useful as a calcium supplement comparable with calcium carbonate.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.101-106
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• 2004

This study was conducted to examine the effect of bluefin tuna bone on the bone metabolism of the rats. Weaned 6-week old male rats were fed low-calcium diets for 2 weeks after the adjustment period. Rats were divided into 6 groups and were fed experimental diets for six weeks. Experimental groups were \circled1 Normal calcium: CC (0.5% CaCO$_3$; control) \circled2 TB (bluefin tuna bone powder) \circled3 CT (citrated bluefin tuna bone powder) \circled4 BB (bovine bone powder) \circled5 CL (calcium lactate) \circled6 Low calcium LC (0.15% CaCO$_3$). Low-calcium diet group (LC) showed the lowest calcium retention. There was no differences in calcium excretion in stool and calcium absorption among various calcium sources. Serum calcitonin levels were high in TB, CT and BB group compared to those in CC, CL LC group. Parathyroid hormone and osteocalcin levels showed no differences among experimental groups. Deoxypyridinoline (DPD) levels were significantly higher in LC group than in other groups. Wet weight of the femur were significantly high in TB and CT group, and dry weight of femur showed no differences among normal calcium groups. Bone density of femur in LC group was significantly lower than those of normal calcium feeding group, and TB group showed highest bone density among experimental groups. There was no differences in bone metabolism among various calcium sources. Therefore, it is pointed out that the amount of calcium intake is very important because there was significant differences between normal calcium diet and low calcium diet. According to the results of femur weight, ash, calcium and bone density, it is suggested that bluefin tuna bone have alternative effects to bovine bone powder on the maintenance of bone health.

• The Korean Journal of Nuclear Medicine Technology
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• v.15 no.1
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• pp.25-28
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• 2011

Purpose: The aim of study is to find accuracy of pocket dosimeter in measuring exposed dose in compared with survey meter and to compare exposed dose according as Nuclear medicine exams. Materials and Method: First, radiation dose to point source(185 MBq,370 MBq, ${\ldots}$, 1665 MBq, 1850 MBq) were measured in using a pocket dosimeter and a survey meter. Second, radiation dose to 12 patients injected $^{18}F$-FDG 370 MBq were measured in using a pocket dosimeter and a survey meter. Third, radiation dose to 10 patients injected $^{99m}Tc$-DPD 925 MBq were measured in using a pocket dosimeter and a surveymeter. Result: The average is $70.12{\pm}39.36{\mu}Sv/h$ in measurement of point source with Surveymeter and $5{\pm}3.06{\mu}Sv$ in measurement of point source with Pocket dosimeter. The average is $25.04{\pm}6.16{\mu}Sv/h$ in measurement of PET/CT patients with Surveymeter and $2.41{\pm}0.51{\mu}Sv$ in measurement of PET/CT with Pocket dosimeter. The average is $8.58{\pm}0.96{\mu}Sv/h$ in measurement of Bone Scan patients with Surveymeter and $1{\mu}Sv$ in measurement of Bone Scan patients with Pocket dosimeter. Significant difference found between Survey meter value and Pocket dosimeter value in all experimentation (p<0.001). Conclusion: Accoring to rusult Wearing Pocket dosimeter is usefulnee in manerage of exposed dose in nucler medicine exams.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.20 no.8
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• pp.813-822
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• 2009

We have investigated operation of a 1:2:2 asymmetric 3-stage Doherty PA(Power Amplifier) and implemented using the Freescale's 4 W, 10 W PEP LDMOSFETS at 1 GHz. By employing the three peak efficiency characteristics, compared to the two peak N-way Doherty PA, the asymmetric 3-stage Doherty can overcome the serious efficiency degradation along the backed-off output power region and maximize the average efficiency for the modulation signal. To maximize the efficiency characteristic, the inverse class F PA has been designed as carrier and peaking amplifiers. Furthermore, to extract the proper load modulation operation, the adaptive gate bias control signal has been applied to the two peaking PAs based on the envelope tracking technique. For the 802.16e Mobile WiMAX(World Interoperability for Microwave Access) signal with 8.5 dB PAPR(Peak to Average Power Ratio), the proposed Doherty PA has shown 55.46 % of high efficiency at an average output power of 36.85 dBm while maintaining the -37.23 dB of excellent RCE(Relative Constellation Error) characteristic. This is the first time demonstration of applying the saturated PA and adaptive gate bias control technique to the asymmetric 3-stage Doherty PA for the highly efficient transmitter of the base-station application.