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Enhanced Dissolution and Permeation of Biphenyl Dimethyl Dicarboxylate Using Solid Dispersions (고체분산체로부터 비페닐디메칠디카르복실레이트의 용출 및 투과 증전)

  • Moon, Jee-Hyun;Chun, In-Koo
    • Journal of Pharmaceutical Investigation
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    • v.29 no.3
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    • pp.227-234
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    • 1999
  • Solid dispersions were prepared to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) using water-soluble carriers such as povidone, copolyvidone, $2-hydroxypropyl-{\beta}-cyclodextrin (HPCD)$, sodium salicylate or sodium benzoate by solvent evaporation method. Solid dispersions were characterized by infrared spectrometry, differential scanning calorimetry (DSC) and powder X-ray diffractometry, dissolution and permeation studies. DDB tablets (7.5 mg) were prepared by compressing the powder mixtures composed of solid dispersions, lactose, com starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were also prepared by filling the mixtures in empty hard gelatin capsules (size No.1). From the DSC and powder x-ray diffractometric studies, it was found that DDB was amorphous in the HPCD or copolyvidone solid dispersions. Dissolution rates after 10 min of DDB alone and solid dispersions (1 : 10) in sodium benzoate, sodium salicylate and copolyvidone were 11.8, 23.5, 22.8 and 82.5%, respectively. Dissolution rates of DDB after 30 min from 1 : 10 and 1 : 20 copolyvidone solid dispersions were 80.5 and 95.0%, respectively. For the DDB tablets prepared using solid dispersions (1 : 20), the initial dissolution rate was dependent on carrier material, and was ranked in order, $Kollidon\;30\;{\ll}$ copolyvidone < HPCD. For the HPCD solid dispersion tablets, dissolution rate reached 97.4% after 15 min, but thereafter slowly decreased to 80.7% after 2 hr due to the precipitation of DDB. However, in the case of copolyvidone solid dispersion tablets, dissolution increased linearly and reached 93.4% after 2 hr. Reducing the volume of test medium from 900 to 300 ml markedly decreased the dissolution rate of the tablets containing 1 : 20 HPCD solid dispersions and 1 : 10 copolyvidone solid dispersion. For 1 : 20 copolyvidone solid dispersion tablets, there was no significant change in dissolution rate up to 1 hr with different volumes of test medium. Preparation of the copolyvidone solid dispersion (1 : 20) in capsules markedly delayed the dissolution (31.2 % after 2hr) due to the limited diffusion within capsules. The permeation rate $(13.4\;g/cm^2\;after\;8\;hr)$ of DDB through rabbit duodenal mucosa from copolyvidone solid dispersion (1 : 10) was markedly enhanced, when compared with drug alone or physical mixtures. From overall findings, DDB formulations containing copolyvidone solid dispersions (1 : 20) could be used to remarkably improve the dissolution rate in dosage form of powders and tablets.

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Tandem Mass Spectrometric Analysis for Disorders in Amino, Organic and Fatty Acid Metabolism : 2 Years of SCL Experience in Korea

  • Yoon, Hye-Ran;Lee, Kyung Ryul
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.3 no.1
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    • pp.86-93
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    • 2003
  • Background : The SCL began screening of newborns and high risk group blood spots with tandem mass spectrometry (MS/MS) in April 2001. Our goal was to determine approximate prevalence of metabolic disorders, optimization of decision criteria for estimation of preventive effect with early diagnosis. This report describes the ongoing effort to identify more than 30 metabolic disorders by MS/MS in South Korea. Methods : Blood spot was collected from day 2 to 30 (mostly from day 2 to 10) after birth for newborn. Blood spot of high risk group was from the pediatric patients in NICU, developmental delay, mental retardation, strong family history of metabolic disorders. One punch (3.2 mm ID) of dried blood spots was extracted with $150{\mu}L$ of methanol containing isotopically labelled amino acids (AA) and acylcarnitines (AC) internal standards. Butanolic HCl was added and incubated at $65^{\circ}C$ for 15 min. The butylated extract was introduced into the inlet of MS/MS. Neutral loss of m/z 102 and parent ion mode of m/z 85 were set for the analyses of AA and AC, respectively. Diagnosis was confirmed by repeating acylcarnitine profile, urine organic acid and plasma amino acid analysis, direct enzyme assay, or molecular testing. Results : Approximately 31,000 neonates and children were screened and the estimated prevalence (newborn/high risk group), sensitivity, specificity and recall rate amounted to 1:2384/1:2066, 96.55%, 99.98%, and 0.73%, respectively. Confirmed 28 (0.09%) multiple metabolic disorders (newborn/high risk) were as follows; 13 amino acid disorders [classical PKU (3/4), BH4 deficient-hyperphenylalaninemia (0/1), Citrullinemia (1/0), Homocystinuria (0/2), Hypermethioninemia (0/1), Tyrosinemia (1/0)], 8 organic acidurias [Propionic aciduria (2/1), Methylmalonic aciduria (0/1), Isovaleric aciduria (1/1), 3-methylcrotonylglycineuria (1/0), Glutaric aciduria type1 (1/0)], 7 fatty acid oxidation disorders [LCHAD def. (2/2), Mitochondrial TFP def. (0/1), VLCAD def. (1/0), LC3KT def. (0/1). Conclnsion : The relatively normal development of 10 patients with metabolic disorders among newborns (except for the expired) demonstrates the usefulness of newborn screening by MS/MS for early diagnosis and medical intervention. However, close coordination between the MS/MS screening laboratory and the metabolic clinic/biochmical geneticists is needed to determine proper decision of screening parameters, confirmation diagnosis, follow-up scheme and additional tests.

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Springback Minimization using Bottoming in Al Can Deep Drawing Process (알루미늄 캔 딥드로잉에서 Bottoming을 이용한 스프링백 최소화)

  • Park, Sang-Min;Lee, Sa-Rang;Hong, Seokmoo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.9
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    • pp.302-307
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    • 2016
  • The technology of multistage deep drawing has been widely applied in the metal forming industry, in order to reduce both the manufacturing cost and time. A battery can used for mobile phone production is a well-known example of multistage deep drawing. It is very difficult to manufacture a battery can, however, because of its large thickness to height aspect ratio. Furthermore, the production of the final parts may result in assembly failure due to springback after multistage deep drawing. In industry, empirical methods such as over bending, corner setting and ironing have been used to reduce springback. In this study, a bottoming approach using the finite element method is proposed as a practical and scientific method of reducing springback. Bottoming induces compression stress in the deformed blank at the final stroke of the punch and, thus, has the effect of reducing springback. Different cases of the bottoming process are studied using the finite element program, DYNAFORM, to determine the optimal die design. The results of the springback simulation after bottoming were found to be in good agreement with the experimental results. In conclusion, the proposed bottoming method is expected to be widely used as a practical method of reducing springback in industry.

Effects of Transverse Cracks on Stress Distributions of Continuously Reinforced Concrete Tracks Subjected to Train Loads (연속철근 콘크리트궤도의 횡균열이 열차 하중에 의한 응력 분포에 미치는 영향)

  • Bae, Sung Geun;Choi, Seongcheol;Jang, Seung Yup;Cha, Soo Won
    • Journal of the Korean Society for Railway
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    • v.17 no.5
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    • pp.355-364
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    • 2014
  • The restrained volume changes of concrete due to variations of temperature and moisture produce transverse cracks in continuously reinforced concrete tracks (CRCTs). Such cracks are known to significantly affect the behaviors and long-term performance of CRCT. To investigate the effects of the transverse cracks on the behavior of CRCT and to develop more reasonable maintenance standards for cracks, in this study, the stress distribution of the track concrete layers (TCL) and the hydraulically stabilized base course (HSB) with transverse cracks were numerically predicted by a three dimensional finite element analysis when CRCT was subjected to train loads. The results indicate that the bending stresses of TCL and vertical stresses at the interfaces between TCL and HSB increased as the cracks were deepened. In addition, vertical stresses were locally concentrated near reinforcing steel in cracks in TCL when full-depth cracks developed, which may lead to punch-outs in CRCTs. Comparably, the effects of crack width and spacing were not as significant as crack depth. This study indicates that ensuring the long-term performance of CRCTs requires adequate maintenance not only for crack width and spacing but also for crack depth. Our results also show that locating HSB joints between sleepers is beneficial to the long-term performance of CRCTs.

Effect of Astragali Radix Pharmacocupuncture for Wound Healing of Full-Thickness Skin Wound in Mouse (황기약침이 전층피부손상 마우스의 치유에 미치는 영향)

  • Hong, Chang-Ho;Kang, Kyung-Hwa;Yoon, Hwa-Jung;Yoon, Hyoun-Min;Song, Choon-Ho;Kim, Cheol-Hong
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.31 no.1
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    • pp.22-31
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    • 2018
  • Objectives : In this study, we investigated whether Astragali Radix Pharmacocupuncture (ARP) has an effective on the full thickness defect wound healing process of mouse. Methods : A total of 50 mice (ICR mouse, 7 week-old male) were divided into control group and ARP group. A single full thickness skin defect was made on the dorsal side of the each mouse using an 8mm diameter biopsy punch. Control group were treated with 0.2㎖ saline and ARP group were treat with 0.2ml ARP at 8 points around the wound every three days total 4 times during the experimental period. The change in wound size, contraction rate, healing rate, and epithelization rate was measured by digital images taken on days 3, 6, 9, and 13, and evaluated using a digital image analysis program. Tissues were collected for histological analysis, RT-PCR, and Western blot on days 3, 6, 9, and 15. Results : The results are as follows. ARP group accelerated the rate of wound contraction, wound healing and epithelization compared to the control group. ARP group showed the decrease of inflammatory cells in early inflammatory phase compared to the control group. ARP group upregulated PECAM-1 mRNA and protein expression compared to the control group. ARP group inhibited the scar width and area compared to the control group. Conclusions: ARP showed positive effects on wound healing through the inhibition of inflammatory reaction and increase of PECAM-1 expression related to the wound healing process.

The Effects of Samul-tang-ga-dansam for Wound Healing (사물탕(四物湯) 가(加) 단참(丹參)의 상처 치료에 대한 효과)

  • Eun-Byeol Lee;Hyeon-Ji Kim;Chae-Young Kim;Ji-Su Choi;Chang-Hoon Woo;Young-Jun Kim;Hee-Duk An
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.2
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    • pp.1-18
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    • 2023
  • Objectives The purpose of this study was to evaluate the antioxidant, anti-inflammatory and wound healing effects of Samul-tang-ga-dansam water extract (SD) in wound-induced mice. Methods The mice were divided into five groups (n=7): the normal group, the control group, the positive control group, the low-dose SD group and the high-dose SD group. The normal group had no wounds and the other groups were wounded on the back with a leather punch. Distilled water was administered to the control group, 200 mg/kg of vitamin E was administered to the positive control group. In the low-dose SD group and the high-dose SD group, 1.23 g/kg and 2.47 g/kg of SD were administered, respectively. Antioxidant and anti-inflammatory protein levels were evaluated using western blot analysis. Skin tissue was analyzed by H&E, Masson's trichrome staining method. Results Oral administration of the SD significantly reduced the visible skin damage and decreased the reactive oxygen species and ONOO- activity of the serum. It significantly increased heme oxygenase-1, superoxide dismutase, catalase, GPx-1/2, Nrf2 and Keap-1 which are antioxidant-related factors in skin tissue and reduced NF-κB p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor α, interleukin (IL)-1β, IL-6 which are inflammation-related factors. Also, SD significantly decreased NOX2, p22phox and p47phox and increased α-smooth muscle actin and COL1A1 protein expression in fibroblasts involved in connective tissue repair. According to histological examination, the thickened epithelial layer was thinned and collagen fibers were increased to accelerate wound healing. Conclusions It is suggested that Samul-tang-ga-dansam has antioxidant and anti-inflammatory effects and promotes wound tissue repair.

A New Access Certification System with Temporal Key Stroke Information (키 입력 시간차이를 이용한 새로운 접속인증 시스템 소개)

  • Choi, Wonyong;Kim, Sungjin;Heo, Kangin;Moon, Gyu
    • Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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    • v.5 no.4
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    • pp.45-53
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    • 2015
  • In this paper, an approach of temporal certification system that can be easily added on current character-based certification system is newly introduced. This technique enhances the security of the password certification process by exploiting temporal information for each character's stroke timing, and using them as another feature of certification information, on top of character comparison process. There are three different temporal conditions: maximum, minimum and no-option. The maximum condition along with a time number (usually 0.2 second or less) means that the next key input should be punched within the time limit, while the minimum condition means the next key stroke should be typed after the time lapse specified. With no-option condition chosen, user can punch the password without any timing constraints. Prototype was developed and tested with four number password case. In comparison with 104 cases, this new approach increases the cases more than 10 digits, enhancing the security of the certification process. One big advantage of this new approach is that user can update his/her password only with different timing constraints, still keeping the same characters, that will enhance the security system management efficiency in a very simple way. Figures and pictures along with process flow are included for the validity of the idea.

Integrity evaluation of rock bolts in the field by using hammer-impact reflection method (해머 타격 반사법을 이용한 현장 록볼트 건전도 평가)

  • Yu, Jung-Doung;Bae, Myeong-Ho;Lee, Yong-Jun;Min, Bok-Ki;Lee, In-Mo;Lee, Jong-Sub
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.11 no.1
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    • pp.47-56
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    • 2009
  • Rock bolts and shotcrete play a crucial role as a main support system in the underground space. Thus, the safety of the underground space may be affected by the defect of rock bolts. In order to evaluate the rock bolt integrity by using non-destructive technique, the transmission method of the guided ultrasonic waves, which are generated by using the piezo disk elements has been successfully performed. The energy generated by the piezo disk elements, however, is not enough for the rock bolts in the field. In addition, the piezo disk elements should be installed at the end of the steel bar during construction of the rock bolts. The purpose of this study is the devolvement of the reflection method, which may generate enough energy, and the application in the field rock bolts. Both laboratory and field tests are carried out. The guided ultrasonic waves with high energy are generated by the hammer impact with the center punch, and the AE sensor is used to measure the reflected guided waves. The received guided waves are analyzed by the wavelet transform. The peak value of the wavelet transform produces the energy velocity, which is used for the evaluation of the rock bolt integrity. The energy velocity increases with an increase in the defect ratio in both laboratory and field rock bolts. This study demonstrates that the hammer-impact reflection method may be a suitable method for the evaluation of the rock bolt in the field.

Heterogeneous Sensor Coordinate System Calibration Technique for AR Whole Body Interaction (AR 전신 상호작용을 위한 이종 센서 간 좌표계 보정 기법)

  • Hangkee Kim;Daehwan Kim;Dongchun Lee;Kisuk Lee;Nakhoon Baek
    • KIPS Transactions on Software and Data Engineering
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    • v.12 no.7
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    • pp.315-324
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    • 2023
  • A simple and accurate whole body rehabilitation interaction technology using immersive digital content is needed for elderly patients with steadily increasing age-related diseases. In this study, we introduce whole-body interaction technology using HoloLens and Kinect for this purpose. To achieve this, we propose three coordinate transformation methods: mesh feature point-based transformation, AR marker-based transformation, and body recognition-based transformation. The mesh feature point-based transformation aligns the coordinate system by designating three feature points on the spatial mesh and using a transform matrix. This method requires manual work and has lower usability, but has relatively high accuracy of 8.5mm. The AR marker-based method uses AR and QR markers recognized by HoloLens and Kinect simultaneously to achieve a compliant accuracy of 11.2mm. The body recognition-based transformation aligns the coordinate system by using the position of the head or HMD recognized by both devices and the position of both hands or controllers. This method has lower accuracy, but does not require additional tools or manual work, making it more user-friendly. Additionally, we reduced the error by more than 10% using RANSAC as a post-processing technique. These three methods can be selectively applied depending on the usability and accuracy required for the content. In this study, we validated this technology by applying it to the "Thunder Punch" and rehabilitation therapy content.

Optimized Controlled Atmosphere Regimen for Storage of Fresh Fischer's Ligularia (Ligularia fischeri Turcz.) Leaves (신선 곰취(Ligularia fischeri Turcz.) 잎 저장을 위한 CA 조성 최적화)

  • Park, Yoon-Moon;Kim, Taewan;Kim, Hyun-Seok;Kim, Tae Hoon;Park, Yoo Jin
    • Horticultural Science & Technology
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    • v.33 no.3
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    • pp.375-382
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    • 2015
  • A controlled atmosphere (CA) regimen was optimized during 3 consecutive harvest seasons as the basis of practical modified atmosphere packaging (MAP) storage for quality maintenance and extension of storage potential of fresh Ligularia fischeri leaves. Leaves were harvested in April or May and forced-air cooled to $4^{\circ}C$ before punch-hole MAP (control, where gas concentrations were same as air) and CA treatments. CA regimens adjusted stepwise during 3 experimental years were: 1 and 3% $O_2$, respectively combined with 5 and 10% $CO_2$ in the first year, 3% $O_2$ fixed in combination with 0, 2.5, and 5% $CO_2$ in the second year, and 3% $O_2$ fixed in combination with 2.5 and 5% $CO_2$ in the third year. In the first year, higher incidence of black discoloration was observed with the reduction of respiration under 10% $CO_2$ CA conditions regardless of $O_2$ levels at 1 or 3%. In the second and third year, the incidence of the disorder seemed not to be clearly relevant to CA conditions showing slightly higher incidence only after 4- or 5-week storage + 5-day shelf life. Although texture and appearance quality were maintained better under the 3% $O_2$ + 2.5% $CO_2$condition after 4-week storage + 5-day shelf life, effects of CA on the extension of storage period was slight. Overall results indicated that Ligularia fischeri leaves are very susceptible to $CO_2$ injury. $CO_2$ concentration should be adjusted below 2.5% for safe and effective CA or MAP storage to maintain quality even during short-term storage.