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Rare Disease Research and Orphan Drug Development (희귀질환 연구와 치료제 개발 동향)

  • Lee, Shinhaeng;Lee, Jangik I.
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.1
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    • pp.1-13
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    • 2013
  • 희귀질환이란 일반적으로 그 유병율이 인구 일만 명당 5명 이하인 질환을 말한다. 세계에는 약 7,000여종의 희귀질환이 알려져 있고 학술지에 매 주 대략 5종의 새로운 희귀질환이 보고되고 있다. 희귀 의약품(orphan drug)이란 희귀질환치료제 또는 수익성이 없어 개발을 기피하는 일반질환 치료제로서 정부가 지정한 의약품을 말한다. Orphan 의약품의 개발에는 많은 장점이 있다. Orphan 의약품으로 정부의 지정을 받으면 세금감면을 통한 연구비 지원, 임상시험 비용 지원, 신약허가 심사비 면제, 시장독점권 부여 등의 특혜가 주어진다. 희귀질환의 대부분은 단순한 유전적 결함에 의하는 경우가 많아 치료제의 표적발견이 비교적 쉬우므로 개발 성공률이 높고, 임상시험기간이 짧으며, 시판허가를 받을 확률이 높아 연구개발비용이 적게 든다. 그 결과 전세계 orphan 의약품 시장은 최근 매년 6%씩 성장하여 2014년에는 약 1,120억달러의 시장을 형성할 것으로 추정된다. Orphan 의약품 시장은 현재 매년 8.9%씩 성장하고 글로벌 시장의 51%를 점유하는 미국을 중심으로 확장되어 가고 있으며, 총매출액의 64.3%가 유전자재조합의약품에 의한 것으로 알려져 있다. 이러한 의약품시장의 변화와 사회적 요구에 부응하여 한국 또한 희귀질환 치료제 개발의 활성화를 위해 재정적 지원체계를 구축하고, 허가관리를 개선하며, 법률적 제도를 완비하는 과정에 있다. 현재 희귀질환의 치료적 타겟을 찾아 신물질이나 기존의 약물을 발굴하는 과정이 주로 대학이나 연구 중심 병원에서 이루어지고 있다. 제도가 잘 정립되어 있는 미국 시장을 겨낭하여 orphan 의약품 개발을 전략적으로 수행한다면 큰 성공을 거둘 수 있을 것으로 기대된다.

An Experimental Study on Charateristics of Autogenous Shrinkage of HPFRCC considering Early Age Coefficient of Thermal Expansion (초기재령에서 열팽창계수를 고려한 고성능 섬유보강 시멘트 복합체의 자기수축 특성에 관한 실험적 연구)

  • Park, Jung-Jun;Moon, Jae-Heum;Park, Gi-Joon;Lee, Jang-Hwa;Kim, Sung-Wook
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.5
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    • pp.3602-3609
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    • 2015
  • HPFRCC is characterized by a very low water-to-binder ratio which induce extremely large autogenous shrinkage at early age. The restriction of such autogenous shrinkage through the use of forms and reinforcing bars will increase substantially the risk of excessive residual stresses and shrinkage cracking. The exact understanding of the shrinkage behavior and studies on solutions to reduce shrinkage should be imperatively undertaken for further application of HPFRCC to real structures. Therefore, this paper investigated the mechanical properties of HPFRCC with respect to the eventual introduction of expansive admixture(EA) and shrinkage reducing agent (SRA) in the mixture. Autogenous shrinkage test was conducted considering the coefficient of thermal expansion (CTE) measured at early age so as to examine the effects of EA and SRA on the autogenous shrinkage behavior of HPFRCC.

Treatment Level of Neem Product for the Control of Bemisia tabaci in the Environmental Friendly Agriculture of Eggplant (가지 담배가루이 방제를 위한 Neem제 처리농도 설정)

  • Kim, Ju;Choi, In-Young;Kim, Ju-Hee;Lee, Jang-Ho;Cheong, Seong-Soo
    • Korean Journal of Organic Agriculture
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    • v.22 no.3
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    • pp.435-444
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    • 2014
  • This experiment was carried out to develop an environmental friendly agriculture material (EFAM) using neem extract i.e. azadirachtin (0.5%), especially against Bemisia tabaci (Gennadius) in eggplant. Neem product was found to be very effective against both nymph and adult of B. tabaci. Yield and economic value of eggplant treated with neem extract were higher than other EFAMs used. Effect of different concentration of Neem product was also investigated on population density of B. tabaci. The growth and yield of eggplants were highest in plants treated with 500 times concentrated solution of neem product. Economic analysis showed that the income increased by 13,545 thousand won/10a from the plots treated with 500 times concentrated solution of neem product over control. The results suggested that 500 times concentrated solution of EFAM (azadirachtin 0.5%) could be a good controlling agent of B. tabaci in eggplants.

Herbicide Combinations of Oxyfluorfen and Paraquat for Early and Late Post-emergence Uses in Pear Orchard (배(梨) 과수원(果樹園)의 잡초방제(雜草防除)를 위한 제초제(除草劑) Oxyfluorfen과 Paraquat의 혼용효과(混用效果)에 관한 연구(硏究))

  • Guh, J.O.;Kim, K.W.;Pyon, J.Y.;Kim, I.K.
    • Korean Journal of Weed Science
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    • v.2 no.2
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    • pp.160-168
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    • 1982
  • Nine combined dosal levels of Paraquat and Oxyfluorfen were compared on pear orchard to control Digitaria adscendens Henr, and others, namely Commelina communis L., Erigeron annuus L., Echinochloa crusgalli P. Beauv var. oryzicola Ohwi, etc.. By treating as an early-postemergence, the mixtures showed higher control effects than 85% of the whole weeds, but the control effects in the mono-treatments of respective herbicide were only 20% or so. On the other hand, as a late-postemergence, the control rates were fluctuated from 31% to 94%. However, there was no significant difference in Spearman's rank correlation coefficients between both efficacies. Thus indicate that the action style of synergistic effect was not influenced by the application time, and the levels of mixtured dosages should be adjusted by the application times and interfering conditions.

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Study on Imported Case Dimorphic Fungi Isolated from Clinical Specimen in Korea (한국의 임상검체로부터 분리된 해외유입 두 형태 진균에 대한 연구)

  • Lee, Jang Ho;Yu, Sungryul;Koo, Bon-Kyung;Moon, Cheol
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.1
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    • pp.29-36
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    • 2018
  • Dimorphic fungi are characterized by the production of mycelia in the environment or when incubated at lower temperatures ($25{\sim}30^{\circ}C$) on media. The conversion to yeast occurs when invading a human body or when incubated at elevated temperatures ($35{\sim}37^{\circ}C$). Dimorphic fungi cause systemic infection and occur only in endemic regions; they can cause deep mycosis, which invades tissues and organs. Imported thermally dimorphic fungal pathogen has five genera, such as Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, Talaromyces (Penicillium) marneffei, and Paracoccidioides brasiliensis. Thus far, 30 cases of dimorphic fungi have been reported in Korea, including C. immitis in 18, H. capsulatum in 5, B. dermatitidis in 3, and T. marneffei in 4 cases. Three 3 cases of C. immitis, 2 cases of H. capsulatum, 1 case of B. dermatitidis, and 1 case of Talaromyces (Penicillium) marneffei were reported in Korea, even though no experience of an epidemic was present. None the dimorphic fungi except for Sporothrix schenkii (Dimorphic fungi) occur in Korea but are caused by endemic fungi that can be found only in specific regions and limited areas of foreign countries. Considering the trends of migratory locals and the increasing number of immigrants living in and returning home, the incidence of imported infections is expected to increase.

소 비장유래 macrophage의 체외배양시 IL-I$\alpha$가 TGF-$\beta$의 생산에 미치는 영향

  • 최선호;성환후;장유민;이장희;연성흠;류일선;손동수;유충현
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.88-88
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    • 2002
  • 인공수정 및 수정란기술의 활성화에 따라 소에 있어서 인공수정은 90%이상이 실시되고 있으나, 수정란이식은 수정란의 생산이 안정적이지 않아 활성화에 많은 지장을 초래하고 있다. 이의 원인은 수정란이식에 의한 수태율의 저하가 가장 크며, 수태율 향상을 위하여 수란우에 progesterone, hCG 등의 주사가 실시되고 있다. 그러나 이는 수정란의 착상에 있어서 자궁의 환경을 개선한다고 하나, 착상의 정확한 기전의 구명은 미미한 상태이다. 한편 비장유래 macrophage가 황체를 자극하고 TGF-$\beta$의 생산을 유도하는 것으로 보고되고 있으며, IL-I $\alpha$$\beta$에 따라 TGF-$\beta$ 생산에 있어서 약간의 차이를 보이는 것으로 보고되고 있다. 따라서 본 연구는 비장유래 macrophage가 TGF-$\beta$의 생산시 임신관련 Cytokine인 IL-I$\alpha$와의 관계를 조사하기 위하여 실시하였다. 임신 및 비임신 도축 암소의 비장을 채취하여 얼음에 채워 실험실로 운반한 후 비장의 표면을 70%의 알콜로 세척하고, 표피를 벗겨 비장조직을 세절하여 10% FBS+DMEM에 넣어 조직을 눌러 짜면서 조직속의 세포를 분리하였다. 세척한 배양액은 4-5$m\ell$를 100mm 유리 petri dish에 넣고 39$^{\circ}C$, 5% $CO_2$, 95% 공기인 배양기에서 2시간이상 배양하였으며, 배양 후 냉장된 buffer A 용액으로 세척하여 유리 petri dish의 바닥에 부착된 macrophage만을 cell scraper로 분리하였다. 분리한 macrophage는 0.5-1 $\times$ $10^{6}$ cells/$m\ell$가 되게 조정하여, IL-I 을 0.001, 0.01, 0.1 또한 1 ng/$m\ell$를 첨가하여 농도에 따른 효과를 조사하였고, 각각 24, 48, 72, 96 또한 120시간을 배양하여 시간에 의한 효과도 실시하였다. 각 배치구에서 얻어진 배양액은 TGF-$\beta$를 조사하기 전까지 -2$0^{\circ}C$에 동결 보존하였다. TGF-$\beta$의 측정은 TGF-$\beta$ kit(promega, USA)를 이용하여 실시하였으며, 통계학적 분석은 Anova test를 Statview program을 이용하여 분석하였다. 시험의 결과 대조구에 비해 IL-I 첨가구는 2-3배의 TGF-$\beta$생산을 보였으며, 배양시간에 따른 생산은 시간이 지남에 따라 약간 상승하는 경향을 보였으나, 유의적인 차이를 보이지는 않았다. 또한 IL-I의 농도에 따른 생산의 변화는 IL-I의 농도에 따라 약간의 차이를 보였고 유의적인 차이는 인정되지 않았다. 임신 및 비임신의 경우 임신우의 비장 macrophage가 비임신보다는 약간 상승하는 거스로 나타났다. 이상의 결과로 볼 때 IL-I $\alpha$$\beta$subunit 보다 TGF-$\beta$ 생산에 있어서 서로 다른 양상을 보일 것으로 추정되며, IL-I은 macrophage의 직접적인 영향을 주기보다는 황체세포를 매개로 한 자궁에 TGF-$\beta$의 생산을 유도하는 것으로 사료되며, 임신관련 cytokine에 대한 다양한 연구가 요구되고 있다.

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Study on Mechanical Properties of Geopolymer Concrete using Industrial By-Products (산업부산물을 사용한 지오폴리머 콘크리트의 역학적 특성에 관한 연구)

  • Kim, Si-Hwan;Koh, Kyung-Taek;Lee, Jang-Hwa;Ryu, Gum-Sung
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.2 no.1
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    • pp.52-59
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    • 2014
  • This study examines the compressive strength, elastic modulus and splitting tensile strength of geopolymer concrete in order to evaluate its mechanical characteristics according to the admixing of fly ash and blast furnace slag. Moreover, identical tests are also conducted considering the amount of powder, the mixing ratio of alkali activator and the mixing ratio of silica fume for further comparative analysis considering various variables. The comparison with the formulae specified in Korean and overseas codes reveal that a mixing ratio of 18% is adequate for the alkali activator and that a replacement ratio of 5% by silica fume is recommended for silica fume. The elastic modulus of the geopolymer concrete appears to increase slightly with the increase of the compressive strength per variable and age and to be smaller than the values predicted by the formulae specified in Korean and overseas codes. In addition, the examination of the stress-strain curves shows that the geopolymer concrete exhibits ductile behavior compared to the conventional OPC. In view of the splitting tensile strength, high strength is observed for a powder content of $400kg/m^3$ and a replacement ratio of 18% by silica fume. The resulting ratio of the compressive strength to the splitting tensile strength is seen to range between 8.7 and 10.2%.

Studies on Early Selection of Excellent Gilts for Improvement of Reproductive Efficiency I. First Estus and Litter Size of Candidate Gilts (번식효율 증진을 위한 후보 종빈돈의 조기선발에 관한 연구 I. 후보 종빈돈의 첫발정 일령과 산자수)

  • 손동수;이장희;최선호;연성흠;류일선;서국현;허태영;박성재;조규호
    • Journal of Embryo Transfer
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    • v.18 no.3
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    • pp.249-255
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    • 2003
  • These studies were performed to improve the reproductive efficiency of gilts and we investigated the effects of puberty periods, first mating time and backfat thickness and will adapt to these results for early selection of excellent gilts. The main results were as follows; 1. First heats on birth season were showed 194.14 day, 163.25 day, 160.25 day and 157.92 day at birth of spring, summer, autumn and winter, respectively and birth of spring was significantly latest among other seasons (p<0.01). 2. First service on birth season were revealed 222.05 day in spring, 193.00 day in summer, 199.20 day in autumn and 190.11 day in winter. birth of spring was significantly latest among others (p<0.01). 3. First heat period of cadidated gilt had 13∼16 mm backfat thickness was 180.32 day, 171.24 day in 17∼20 mm and 162.20 day in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness. 4. First service of cadidate gilt had 13∼16mm backfat thickness was 211.12 day, 202.43 day in 17∼20 mm and 195.43 day in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness. 5. The litter size were 9.64 in gilts under 160 day of first heat, 10.14 in 161∼180 day, 9.56 in 181∼200 day and 9.13 in over 201 day. There showed the largest litter size in 161∼180 day of first heat but was no differences. 6. The litter size in gilts under 180 day of first service was 9.13, 9.75 in 181∼200 day, 10.13 in 201∼220 day and 9.45 in over 221 day. There showed the largest litter size in 201∼220 day of first service but was no differences. 7. The litter size of gilt had 13∼16 mm backfat thickness on first service was 9.33, 9.81 in 17∼20 mm and 10.17 in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness.

A Study on the Sensory Characteristics of Korean Red Wine (한국산 적포도주의 관능적 특성에 관한 연구 (III))

  • Lee, Jang-Eun;Hong, Hee-Do;Choi, Hee-Don;Shin, Yong-Sub;Won, Yoo-Dong;Kim, Sung-Soo;Koh, Kyung-Hee
    • Korean Journal of Food Science and Technology
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    • v.35 no.5
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    • pp.841-848
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    • 2003
  • The sensory characteristics of red wine Gerbong (G), Campbell (C), Moru (M), Gerbong + Moru (70 : 30, GM), Gerbong + Campbell (70 : 30, GC) and French wine (F, Carbernet Sauvignon, 1998) were evaluated. The preferences of color, flavor, taste and total evaluation were determined by a ranking test, and the organoleptic characteristics were evaluated by a quantitative descriptive analysis (QDA) method. The mean color scores of C, GM, F, GC, M and G were 4.74, 3.94, 4.67, 3.70, 2.65 and 1.47, respectively (p<0.001). The order for the mean score for flavor was GM (4.12) = M (3.94) = C (3.76) = F (3.76) ${\geq}$ GC (3.12)>G (2.29) (p<0.01), and the order for taste was F (4.75) ${\geq}$ C (4.25) ${\geq}$ GM (3.37) = GC (3.50) ${\geq}$ G (2.75) = M (2.37) (p<0.001). The total evaluation of mean scores showed G, M, C, GM, GC and F were 237, 2.44, 4.06, 3.87, 3.64 and 4.81, respectively (p<0.001). Influences of sensory characteristics on the total evaluation, in percentages, were 69.3% for taste, 3.7% for color, and 1.5% for flavor. The influences of taste, color, and flavor in red wine were 17% for sweet, acid, bitter and salty taste, 28.9% for purple and red color, and 14.4% for grape flavor. The attributes of the purple and red colors showed a positive correlation with grape flavor, oak flavor, grape taste, and floral tastes, but a negative correlation with $SO_2$, flavor. The attribute of sweet taste showed a positive correlation with grape flavorand floral flavor, but a negative correlation with bitter and astringency tastes, according to Pearsons correlation analysis (p<0.01).

Effect of temperature on oviposition of Spodoptera frugiperda (Lepidoptera: Noctuidae) and ovipositional characteristics in corn fields (온도가 열대거세미나방 산란에 미치는 영향 및 옥수수 포장에서의 산란 특성)

  • Hyung Cheol Moon;Min Kyung Choi;Su Ji Jang;Jang Ho Lee;Ju Hee Kim;Hyong Gwon Chon
    • Korean Journal of Environmental Biology
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    • v.40 no.3
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    • pp.281-289
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    • 2022
  • The effect of five different constant temperatures (18, 21, 24, 27, and 30±1℃) and a photoperiod of 14 : 10 (L :D) h on the reproduction parameters of Spodoptera frugiperda was studied. The longevity of adult female S. frugiperda decreased with increasing temperature (22.4 days at 21℃ and 13.9 days at 30℃) but not at 18℃. The pre-oviposition period and oviposition period was the shortest at 30℃ compared to the other temperatures. The total fecundity egg count was 887.4, 1,246.4, 1,348.9, 1,154.9, and 1,034.2 at 18, 21, 24, 27 and 30℃, respectively, during its life span. The survival rate of female S. frugiperda decreased rapidly after 13 days at 18℃, after 14 days at 21℃, after 15 days at 27℃, and after 9 days at 24℃, and 30℃. On the third day after the start of oviposition, 50% of the total fecundity was accomplished. In corn fields at less than the 10-leaf stage, the distribution of S. frugiperda egg masses was observed in the middle and lower plant regions, corresponding to 46.8% and 41.4% of the total egg masses, respectively. Egg masses were mostly found on the underside of the leaf blade (abaxial) of corn(66.7%). After releasing S. frugiperda adults on May 12, May 17, May 25, and May 30, the number of eggs per egg mass was 89.9, 88.5, 126.6, and 127.9, respectively. Egg masses of the subsequent generations of S. frugiperda were observed from late June, and the number of eggs per egg mass was 155.8 in late June, 270.7 in early July, and 303.5 in mid-July.