• Title/Summary/Keyword: Phase I study

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Effect of Bevacizumab on Human Tenon's Fibroblasts Cultured from Primary and Recurrent Pterygium

  • Park, Young Min;Kim, Chi Dae;Lee, Jong Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.4
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    • pp.357-363
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    • 2015
  • The purpose of this study was to compare the inhibitory effect of bevacizumab on human Tenon's fibroblasts (HTFs) cultured from primary and recurrent pterygium. Cultured HTFs were exposed to 2.0, 5.0, 7.5, and 15.0 mg/mL concentration of bevacizumab for 24 hours. The 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assays were then performed to assess fibroblast metabolism and viability. The matrix metalloproteinase (MMP), procollagen type I C terminal propeptide (PIP), and laminin immunoassays were performed to examine extracellular matrix production. Changes in cellular morphology were examined by phase-contrast and transmission electron microscopy. Both metabolic activity and viability of primary and recurrent pterygium HTFs were inhibited by bevacizumab in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. Both types of HTFs had significant decreases in MMP-1, PIP, and laminin levels. Distinctly, the inhibitory effect of bevacizumab on MMP-1 level related with collagenase in primary pterygium HTFs was significantly higher than that of recurrent pterygium. Significant changes in cellular density and morphology both occurred at bevacizumab concentrations greater than 7.5 mg/mL. Only primary pterygium HTFs had a reduction in cellular density at a bevacizumab concentration of 5.0 mg/mL. Bevacizumab inhibits primary and recurrent pterygium HTFs in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. As the primary HTFs produces larger amounts of MMP-1 compared to recurrent HTFs, significant reduction in MMP-1 level in primary pterygium HTFs after exposure to bevacizumab is likely to be related to the faster cellular density changes in primary pterygium HTFs.

A Boundness Analysis of Performance on the Nested Queueing Network with Population Constraint (용량제한을 갖는 중첩형 대기행렬 네트워크의 성능 범위분석)

  • Rhee, Young
    • Journal of KIISE:Computer Systems and Theory
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    • v.36 no.4
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    • pp.239-246
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    • 2009
  • In this study, we analyze the mean waiting time on the nested open queueing network, where the population within each subnetwork is controlled by a semaphore queue. The queueing network can be transformed into a simpler queueing network in terms of customers waiting time. A major characteristic of this model is that the lower layer flow is halted by the state of higher layer. Since this type of queueing network does not have exact solutions for performance measure, the lower bound and upper bound on the mean waiting time are checked by comparing them with the mean waiting time in the transformed nested queueing network. Simulation estimates are obtained assuming Poisson arrivals and other phase-type arrival process, i.e., Erlang and hyper-exponential distributions. The bounds obtained can be applied to get more close approximation using the suitable approach.

New Strategy for Eliminating Zero-sequence Circulating Current between Parallel Operating Three-level NPC Voltage Source Inverters

  • Li, Kai;Dong, Zhenhua;Wang, Xiaodong;Peng, Chao;Deng, Fujin;Guerrero, Josep;Vasquez, Juan
    • Journal of Power Electronics
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    • v.18 no.1
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    • pp.70-80
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    • 2018
  • A novel strategy based on a zero common mode voltage pulse-width modulation (ZCMV-PWM) technique and zero-sequence circulating current (ZSCC) feedback control is proposed in this study to eliminate ZSCCs between three-level neutral point clamped (NPC) voltage source inverters, with common AC and DC buses, that are operating in parallel. First, an equivalent model of ZSCC in a three-phase three-level NPC inverter paralleled system is developed. Second, on the basis of the analysis of the excitation source of ZSCCs, i.e., the difference in common mode voltages (CMVs) between paralleled inverters, the ZCMV-PWM method is presented to reduce CMVs, and a simple electric circuit is adopted to control ZSCCs and neutral point potential. Finally, simulation and experiment are conducted to illustrate effectiveness of the proposed strategy. Results show that ZSCCs between paralleled inverters can be eliminated effectively under steady and dynamic states. Moreover, the proposed strategy exhibits the advantage of not requiring carrier synchronization. It can be utilized in inverters with different types of filter.

Leg Muscle Activity from the Perturbation of the Support during Gait (보행 시 지지 기반 급변에 대한 하지 근신경의 반응)

  • Shin, In-Sik;Chun, Young-Jin;Seo, Jung-Seok;Choi, Chi-Sun;Nam, Ki-Jung
    • Korean Journal of Applied Biomechanics
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    • v.17 no.3
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    • pp.147-154
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    • 2007
  • This study's purpose is to investigate the effects on leg muscle activity caused by perturbation, using a trapdoor system during the support phase of gait for healthy adults (n = 6, height $177.5{\pm}5.5cm$, weight $81.0{\pm}9.5kg$, age $30.0{\pm}3.3yrs$). The trapdoor had the functional ability of causing inversion or eversion. The release time for the trapdoor was specified for two times, 0.3 and 0.5 seconds after heel contact. While altering these variables, EMG was recorded for the leg muscles (rectus femoris, biceps femoris, vastus lateralis, tibialis anterior, gastrocnemius, soleus). The following conclusions were derived. The steptime was longer for the 0.5s eversion than 0.3s inversion condition. So in order to regain stability after the perturbation the unsupporting leg reached forward rapidly. This quick reflex can be observed through the center of pressure (COP) and its rapid change in direction. The gastrocnemius was activated throughout the total experiment. There was a low amount of activity recorded in the rectus femoris, vastus lateralis and tibialis anterior except for the condition of inversion 0.3s. For most of the conditions, the highest average EMG peak values were recorded during the condition of inversion 0.3s. The iEMG patterns were similar for the conditions of inversion 0.3s and eversion 0.3s. To cope with the rapid change in these conditions, the biceps femoris was activated. During the experiment except for the condition of normal gait, the activity of the soleus and gastrocnemius was relatively high. Therefore, to prevent injury from perturbation of the lower leg strengthening of the soleus and gastrocnemius is required. Likewise to prevent injury to the thigh strengthening for the biceps femoris.

Integrated Level 1-Level 2 decommissioning probabilistic risk assessment for boiling water reactors

  • Mercurio, Davide;Andersen, Vincent M.;Wagner, Kenneth C.
    • Nuclear Engineering and Technology
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    • v.50 no.5
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    • pp.627-638
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    • 2018
  • This article describes an integrated Level 1-Level 2 probabilistic risk assessment (PRA) methodology to evaluate the radiological risk during postulated accident scenarios initiated during the decommissioning phase of a typical Mark I containment boiling water reactor. The fuel damage scenarios include those initiated while the reactor is permanently shut down, defueled, and the spent fuel is located into the spent fuel storage pool. This article focuses on the integrated Level 1-Level 2 PRA aspects of the analysis, from the beginning of the accident to the radiological release into the environment. The integrated Level 1-Level 2 decommissioning PRA uses event trees and fault trees that assess the accident progression until and after fuel damage. Detailed deterministic severe accident analyses are performed to support the fault tree/event tree development and to provide source term information for the various pieces of the Level 1-Level 2 model. Source terms information is collected from accidents occurring in both the reactor pressure vessel and the spent fuel pool, including simultaneous accidents. The Level 1-Level 2 PRA model evaluates the temporal and physical changes in plant conditions including consideration of major uncertainties. The goal of this article is to provide a methodology framework to perform a decommissioning Probabilistic Risk Assessment (PRA), and an application to a real case study is provided to show the use of the methodology. Results will be derived from the integrated Level 1-Level 2 decommissioning PSA event tree in terms of fuel damage frequency, large release frequency, and large early release frequency, including uncertainties.

The Influence of Heat Treatment and Ca contents on the Electrochemical Characteristics of Mg-Ca Alloys (Mg-Ca 합금의 전기화학적 특성에 미치는 Ca 첨가량 및 열처리의 영향)

  • Lee, S.H.;Chung, Dong-Seok;Park, B.O.;Kim, Y.G.;Jeong, Ha-Guk;Kim, Hye-Sung
    • Journal of the Korean Society for Heat Treatment
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    • v.17 no.3
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    • pp.173-179
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    • 2004
  • In this study, the influence of heat treatment and Ca contents on the electrochemical behavior was investigated. Mg-Ca alloys, i.e., Mg-0.22wt%Ca, Mg-0.56wt%Ca, Mg-1.31wt%Ca are prepared by ingot metallurgy. As-cast Mg-Ca alloys exhibited better electrochemical properties than pure Mg. Especially, Mg-0.22wt%Ca alloy improves its anode efficiency up to 62% and lowers the OCP up to -1.72VSCE. Microstructure and XRD patterns of Mg-Ca alloys show that additive Ca element is mainly solid-solutioned. While, the others show the microstructure and XRD pattern with large $Mg_2Ca$ at grain boundary. To assess the effect of heat treatment on the as-cast Mg-alloy, the specimens were heat treated at $200^{\circ}C$ for 2 hours under $CO_2$ gas atmosphere. Although corrosion properties of Mg-Ca alloys are somewhat deteriorated by heat treatment at $200^{\circ}C$ Mg-0.22wt%Ca alloy with uniformly distributed nano-sized $Mg_2Ca$ phase in ${\alpha}$-Mg matrix show still better corrosion properties than pure Mg specimen.

Synthesis, Radiolabeling and Gastrin Releasing Peptide Receptor Binding Affinity of a Novel Bombesin Antagonist-Based Peptide, DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2

  • Lim, Jae Cheong;Choi, Sang Mu;Cho, Eun Ha;Kim, Jin Joo
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.127-134
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    • 2013
  • Bombesin receptors are overexpressed in many kinds of human tumors. In particular, the gastrin releasing peptide receptor (GRPR) which is also called bombesin receptor subtype 2, has been identified in prostate cancer. In the present study, we developed a bombesin antagonist-based $^{177}Lu$-labeled peptide, $^{177}Lu$-DOTA-$Ala(SO_3H)$-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-$NH_2$ (DOTA-sBBNA). DOTA-sBBNA was prepared using a solid phase synthesis method. It was labeled with $^{177}Lu$ by a high radiolabeling yield (>98%), and its Log P value was -2.05. The radiolabeled peptide was highly stable in serum incubation at $37^{\circ}C$ for 48 hr. A competitive displacement of $^{125}I-[Tyr^4]$-Bombesin on the PC-3 human prostate carcinoma cells revealed that the $IC_{50}$ value of the peptide was 6.76 nM indicating a highly nanomolar binding affinity for GRPR. These results suggest that $^{177}Lu$-DOTA-sBBNA can be a potential candidate for targeting prostate cancer, and further studies to evaluate its biological characteristics are needed.

Novel Bombesin Analogues Conjugated with DOTA-Ala(SO3H)-4 aminobenzoic acid and DOTA-Lys(glucose)-4 aminobenzoic acid: Synthesis, Radiolabeling, and Gastrin Releasing Peptide Receptor Binding Affinity

  • Lim, Jae Cheong;Choi, Sang Mu;Cho, Eun Ha;Kim, Jin Joo
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.191-200
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    • 2013
  • In this study, a novel bombesin (BBN) analogues, DOTA-Ala($SO_3H$)-4 aminobenzoyl-Gln-Trp-Ala-Val-Gly-His-Leu-Met-$NH_2$ (DOTA-sBBN) and DOTA-Lys(glucose)-4 aminobenzoyl-Gln-Trp-Ala-Val-Gly-His-Leu-Met-$NH_2$ (DOTA-gluBBN), were synthesized and radiolabeled, and their binding affinities were evaluated. Peptides were prepared by a solid phase synthesis method and their purities were over 98%. DOTA is the chelating agent for $^{177}Lu$-labeling, and the DOTA-conjugated peptides were radiolabeled with $^{177}Lu$ by a high radiolabeling yield (>98%). The Log P values of DOTA-sBBN and DOTA-gluBBN were -2.20 and -2.79, respectively. 50.41% of $^{177}Lu$-DOTA-sBBN and 72.97% of $^{177}Lu$-DOTA-gluBBN were left undegraded by the serum incubation at $37^{\circ}C$ for 48 hr. A competitive displacement of $^{125}I-[Tyr^4]$-BBN on the PC-3 human prostate carcinoma cells revealed that 50% inhibitory concentration ($IC_{50}$) were 1.46 nM of DOTA-sBBN and 4.67 nM of DOTA-gluBBN indicating a highly nanomolar binding affinity for GRPR. Therefore, it is concluded that $^{177}Lu$-DOTA-sBBN and $^{177}Lu$-DOTA-gluBBN can be potential candidates as a targeting modality for the Gastrin-releasing peptide receptor (GRPR)-over-expressing tumors, and further studies to evaluate their biological and pharmacological characteristics are needed.

Optimum Combination of Thermoplastic Formability and Electrical Conductivity in Al-Ni-Y Metallic Glass

  • Na, Min Young;Park, Sung Hyun;Kim, Kang Cheol;Kim, Won Tae;Kim, Do Hyang
    • Metals and materials international
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    • v.24 no.6
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    • pp.1256-1261
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    • 2018
  • Both thermoplastic formability and electrical conductivity of Al-Ni-Y metallic glass with 12 different compositions have been investigated in the present study with an aim to apply as a functional material, i.e. as a binder of Ag powders in Ag paste for silicon solar cell. The thermoplastic formability is basically influenced by thermal stability and fragility of supercooled liquid which can be reflected by the temperature range for the supercooled liquid region (${\Delta}T_x$) and the difference in specific heat between the frozen glass state and the supercooled liquid state (${\Delta}C_p$). The measured ${\Delta}T_x$ and ${\Delta}C_p$ values show a strong composition dependence. However, the composition showing the highest ${\Delta}T_x$ and ${\Delta}C_p$ does not correspond to the composition with the highest amount of Ni and Y. It is considered that higher ${\Delta}T_x$ and ${\Delta}C_p$ may be related to enhancement of icosahedral SRO near $T_g$ during cooling. On the other hand, electrical resistivity varies with the change of Al contents as well as with the change of the volume fraction of each phase after crystallization. The composition range with the optimum combination of thermoplastic formability and electrical conductivity in Al-Ni-Y system located inside the composition triangle whose vertices compositions are $Al_{87}Ni_3Y_{10}$, $Al_{85}Ni_5Y_{10}$, and $Al_{86}Ni_5Y_9$.

Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide

  • Han, Jiahong;Xia, Jing;Zhang, Lianxue;Cai, Enbo;Zhao, Yan;Fei, Xuan;Jia, Xiaohuan;Yang, He;Liu, Shuangli
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.618-624
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    • 2019
  • Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside $Rk_3$ ($Rk_3$) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and $Rk_3$ on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and $Rk_3$ could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of $G_0/G_1$ phase cells, and increase the proliferation index. Finally, Re and $Rk_3$ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and $Rk_3$ could improve the hematopoietic function of myelosuppressed mice. The effect of $Rk_3$ was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and $Rk_3$ on myelosuppression.