• Title/Summary/Keyword: ${\mu}-CT$

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Synthesis and Biological Evaluation of Tetrapeptide Ketones as Reversible 20S Proteasome Inhibitors

  • Latif, Muhammad;Jung, Myoung Eun;Lee, Kwangho;Choi, Gildon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.12
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    • pp.3571-3575
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    • 2014
  • Proteasome, a multicatalytic protease complex, has been validated as a promising therapeutic target in oncology. Carfilzomib (Kyprolis$^{(R)}$), a tetrapeptide epoxyketone, irreversibly inhibits the chymotrypsin-like (CT-L) activity of the proteasome and has been recently approved for multiple myeloma treatment by FDA. A chemistry effort was initiated to discover the compounds that are reversibly inhibit the proteasome by replacing the epoxyketone moiety of carfilzomib with a variety of ketones as reversible and covalent warheads at the C-terminus. The newly synthesized compounds exhibited significant inhibitory activity against CT-L activity of the human 20S proteasome. When the compounds were tested for cancer cell viability, 14-8 was found to be most potent in inhibiting Molt-4 acute lymphoblastic leukemia cell line with a $GI_{50}$ of $4.4{\mu}M$. Cytotoxic effects of 14-8 were further evaluated by cell cycle analysis and Western blotting, demonstrating activation of apoptotic pathways.

Clinical animal test for development of osseointegration implant;application for beagle tibia (골융합 임플란트 개발을 위한 동물임상실험;비글견 경골 적용)

  • Choi, Kyong-Joo;Kim, Shin-Ki;Mun, Mu-Seong;An, Jae-Yong
    • Proceedings of the KSME Conference
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    • 2003.11a
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    • pp.1373-1377
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    • 2003
  • Current prostheses for amputees are generally extrinsic wearing socket type that the coupling between body stump and appliance wraps the soft tissue and this structure causes several problems :applying direct weight to soft tissue such as skin and muscle, skin trouble of contacting area and pain. In this study, osseointegration implant is a method to directly connect prosthesis to the residual stump skeletal tissue of arm, finger and leg through surgical operation. Technology presented in this paper essentially solves the problems of pain and abnormal weight transfer system indicated above and recovers the functions of the amputated arm and leg. In this paper, implant shape was designed for the first step for the development of osseointegration implant and then we studied the possibility to apply this osseointegration implant to human body by performing implant insertion operation to beagle tibia for the clinical animal test and normal beagle's gait analysis was executed in order to quantitatively verify the beagle's skeletal functions after the implant insertion.

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Antitumor Effects and Immunomodulating Activities of Phellinus linteus Extract in a CT-26 Cell-Injected Colon Cancer Mouse Model

  • Yang, Byung-Keun;Hwang, Seung-Lark;Yun, Ik-Jin;Do, Eun-Ju;Lee, Won-Ha;Jung, Young-Mi;Hong, Sung-Chang;Park, Dong-Chan
    • Mycobiology
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    • v.37 no.2
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    • pp.128-132
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    • 2009
  • The antitumor effects of Phellinus linteus extract (Keumsa Linteusan) were investigated in a CT-26 cell-injected colon cancer mouse model. When administered orally (250${\sim}$1,000 mg/kg body weight), Keumsa Linteusan significantly inhibited the growth of solid colon cancer. The highest dose was highly effective, reducing tumor formation by 26% compared with the control group. The anticomplementary activity of Keumsa Linteusan increased in a dose-dependent manner. Lysosomal enzyme activity of macrophages was increased by 2-fold (100 ${\mu}$/ml) compared with the control group. Keumsa Linteusan can be regarded as a potent enhancer of the innate immune response, and can be considered as a very promising candidate for antitumor action.

Effects on Mammalian Tissues and Cells by Sulfur Containing Compounds (황함유 화합물이 동물의 조직과 세포에 미치는 영향)

  • 이기섭;이정채;나상록;정희영;임계택
    • Toxicological Research
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    • v.15 no.1
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    • pp.79-87
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    • 1999
  • To know the stress response and antioxidative effect of sulfur containing compounds, we observed the expression of the stress protein (heat shock protein; inducible protein) from mouse tissues and evaluated the protective effects to hydroxyl radical in mouse brain cell culture. Cysteine, methionine or sodium sulfide was fed by oral administration of 1 ml/per 6hr/three times with 1 mM, 2mM or 3mM to mouse, respectively. After that, the stress proteins were extracted from mouse tissues and analyzed the features of expression. The stress proteins by sulfur containing compounds were showed different aspects in the kinds and concentrations of their compounds, and in the tissues of mouse. In the liver, the stress proteins were appeared at different time on the concentration of sulfur containing compounds and had less than 20 KDa as small molecules. In general, the molecular weights of stress protein in liver, the stress proteins were appeared at different time on the concentration of sulfur containing compounds and had less than 20 KDa as small molecules. In general, the molecular weights of stress protein in the spleen were evaluated from 32KDa to 50KDA, and the induced times were relatively late at high concentration of cysteine, early at low concentration of methionine or sodium sulfide. The stress proteins in mouse muscle were detected mostly between 24hr after treatment of sulfur containing compounds. Their molecular weights were 15~24KDa. In the antioxidative effects of sulfur containing compounds to hydroxyl radical, cell viabilities were measured by 63.2% at 10 $\mu\textrm{M}$, 65.5% at 50 $\mu\textrm{M}$, 68.6% at 100 $\mu\textrm{M}$, 78.3% at 150 $\mu\textrm{M}$, or 83.0% at 200 $\mu\textrm{M}$ of cysteine, respectively. At addition of methionine, the cell viabilities were assessed as 58.1% at 10 $\mu\textrm{M}$, 62.8% at 50 $\mu\textrm{M}$, 75.7% at 100 $\mu\textrm{M}$, 78.6% at 150 $\mu\textrm{M}$, and 79.2% at 200 $\mu\textrm{M}$ after 4hrs exposure with 20mU/ml glucose oxidase (GO) system, while the numbers of live cells to hydroxyl radicals in treatment of sodium sulfide were showed 48.6% at 10 $\mu\textrm{M}$, 54.8% at 100 $\mu\textrm{M}$, 51.8% at 150 $\mu\textrm{M}$, and 51.6% at 200 $\mu\textrm{M}$ in the neuronal cells. In the inhibitory effects on the proliferation of tumor cells, percentages of dead cells of the CT-26 or HeLa cell were generally less than 30% even 48hr after addition of sulfur containing compounds. Conclusively, the results of these experiments indicate that stress protein by sulfur containing compounds can be used as physiological indicator for animal nutrition and for environment, and also that cysteine and methionine can play critical roles as an antioxidant.

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Regional Morphological and Mechanical Characteristics in the Human Thoracic Vertebral Trabecular Bones (인체 흉추 해면골의 영역별 형태학적 및 기계적 특성 연구)

  • Lee, Tae-Woo;Woo, Dae-Gon;Ko, Chang-Young;Kim, Han-Sung
    • Journal of the Korean Society for Precision Engineering
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    • v.27 no.1
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    • pp.134-141
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    • 2010
  • This study analyzed the regional morphological and mechanical characteristics of vertebrae by using micro-computed tomography (micro-CT) and micro finite element analysis (FEA). For the present study, the $12^{th}$ human thoracic vertebral bones (an 85-years female and a 48-years male) were used. These were scanned by using micro-CT. Structural parameters were evaluated from the acquired 20 image data for fifteen $4{\times}4mm^2$ regions (five regions in respective layers of superior, middle and inferior part) in the thoracic vertebral trabecular bones. $4{\times}4{\times}4mm^3$ cubic finite element models of each regions were created at $70{\mu}m$ voxel resolution to investigate effective modulus ($E^+$). The present study indicated that there were significant differences in morphological and elastic mechanical characteristics of each region. There are close relationship between effective modulus and structural model index (SMI) in the bone of the 48-years male and between effective modulus and bone volume fraction (BV/TV) in the bone of the 85-years female. In addition, the effective modulus of central regions is about 80% stiffer than that of lateral regions at transverse plane. These findings may be likely to explain the previous result that a change of loading distribution of the vertebral trabecular bones is caused by spinal curvature and nucleus pulpous degeneration of the intervertebral disc.

Automatic Liver Segmentation by using Gray Value Portion in Enhanced Abdominal CT Image (조영제를 사용한 복부CT영상에서 명암값 비율을 이용한 간의 자동 추출)

  • Yu, Seung-Hwa;Jo, Jun-Sik;No, Seung-Mu;Sin, Gyeong-Suk;Park, Jong-Won
    • Journal of the Institute of Electronics Engineers of Korea SP
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    • v.38 no.2
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    • pp.179-190
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    • 2001
  • In this proposed study, observing and analyzing contrast enhanced abdominal CT images, we segmented the liver automatically. We computed the ratio of each gray value from the estimated gray value range. With the average value of mesh image, we distinguished the liver from the noise parts. We divided the region based on immersion simulation. The threshold value is determined from the mesh image which is generated from each gray value portion of the liver and is used in dividing the liver to the noise region. To get the outline of the liver, we generated template image which represents the lump of the liver, and subtracted it from the binary image. With the results we use the proposed algorithm using 8-connectivity instead of the present opening algorithm, to reduce the processing time. We computed the volume from the segmented organ size and presented a clinical demonstration with the animal experiment

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The effect of varying peripheral bone structure and bone density on the occlusal stress distribution of human premolar regions (사람 소구치부위에서 주위골의 구조 및 밀도변화가 교합력에 의한 치아의 응력분포에 미치는 영향)

  • Suh, Ye-Joon;Shim, June-Sung;Lee, Keun-Woo;Chung, Moon-Kyu;Lee, Ho-Yong
    • Journal of Dental Rehabilitation and Applied Science
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    • v.19 no.1
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    • pp.7-15
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    • 2003
  • This study used FEM(Finite Element method) based on micro-CT images to see the effects of occlusal force distribution with varying bone density and structure. the mandibular premolar region from human cadaver, thickness of 10mm was imaged using micro-CT. the cross sectional images were taken every $10{\mu}m$. these were reconstructed and the longitudinal image at the mid point of mesiodistal of the speciman was obtained for the specimen for the FEM. The stress disribution produced by a vertical force at 100N and 100N horizontal were analyzed by MSC Nastran FEM Package. according to the result of this study the occlusal force distribution depends on the structure of cancellus bone and for further information on the occlusal force distribution on the tooth and the surrounding structure requires further studies on cancellus bone structure. CEJ of all model show the highest peak and region whice meet teeth and bone show second high peak. Original model and cortical bone add model show different stress distribution. Stress distribution changed according to bone structures and densities.

Dosimetric Verification for Primary Focal Hypermetabolism of Nasopharyngeal Carcinoma Patients Treated with Dynamic Intensity-modulated Radiation Therapy

  • Xin, Yong;Wang, Jia-Yang;Li, Liang;Tang, Tian-You;Liu, Gui-Hong;Wang, Jian-She;Xu, Yu-Mei;Chen, Yong;Zhang, Long-Zhen
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.985-989
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    • 2012
  • Objective: To make sure the feasibility with $^{18F}FDG$ PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Methods: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and $^{18F}FDG$ PET/CT). The dose distributions of the various regional were realized by SMART. Results: The absolute mean errors of interest area were $2.39%{\pm}0.66$ using 0.6cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Conclusions: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Design and Implementation of Optical Signal Processor in Fiber-Optic Current Transducer for Electric Equipments (전력기기용 고안정성 광섬유 CT 센서의 광 신호처리기 설계 및 구현)

  • Jang, Nam-Young;Choi, Pyung-Suk;Eun, Jae-Jeong;Cheong, Hyeon-Seong
    • Journal of the Institute of Convergence Signal Processing
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    • v.8 no.3
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    • pp.171-177
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    • 2007
  • In this paper, we have designed and implemented an optical signal processor in order to use in a fiber-optic current CT for electric equipments where its properties were discussed. The fabricated optical signal processor is used to reduce a measurement current error that induced by the effects of intensity variation in the optical output signal due to losses coming from optical components or polarization variation in a PFOCS. Also, the optical signal processor was fabricated in compact/lightweight with unification of opto-electronic transducer part, analog signal process part, and real-time measurement part consisted of a level shift and ${\mu}-processor$. The experiment of optical signal processor has been performed in the range of $0{\sim}7,500A$ using the PFOCS made all fiber-optic components. As a result of experiment, the linearity error of measurement current is less than 1.7% and its average error is less than 0.3% in the range of $1,000A{\sim}7,000A$.

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Long-Term Analysis for the effect of Ovariectomy on Rat Bone using Micro Finite Element Method (미세 유한요소법을 이용한 난소제거가 쥐뼈에 미치는 영향의 장기간 분석)

  • Ko C.Y;Woo D.G.;Lee T.W.;Kim H.S.;Lee B.Y.;Tack G.R.
    • Proceedings of the Korean Society of Precision Engineering Conference
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    • 2005.10a
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    • pp.236-239
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    • 2005
  • This study investigated the effect of ovariectomy (OVX) on the rat bone fur long term (22 weeks). In previous researches, there were many studies for morphology of OVX-induced osteoporotic bones based on micro-Computed Tomography (micro-CT). However, there were few studies fpr detecting and tracking changes of mechanical characteristics in the lumbar vertebrae of OVX rat fur long-term. For this study, one female Sprague-Dawley rat was used: an OVX rat. The 4th lumbar of the OVX rat was utilized as a specimen. Morphological characteristics could be investigated fur the lumbar vertebrae in an OVX rat by using in-vivo Micro-CT. An OVX rat was scanned at week 0 (just before surgery), at week 4, at week 8, at week 16 and at week 22 after surgery. Micro finite element $({\mu}FE)$ analysis was used to investigate mechanical characteristics in the lumbar vertebrae for an OVX rat.

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