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The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats

  • Choi, Sang-Joon;Choi, Jun-Shik
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.469-476
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    • 2010
  • This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

Experimental Studies of the Blood Gas Transport during Normothermic Hemodilution Perfusion (상온하 혈액희석 체외순환에 있어서 혈액 GAS 동태에 관한 실험적 연구)

  • 박희철
    • Journal of Chest Surgery
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    • v.13 no.2
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    • pp.85-91
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    • 1980
  • Extracorporeal circulation by hemodilution technique has been currently used with its clinical safety and good peripheral tissue perfusion in open heart surgery. There is no doubt that $O_{2}$ carrying capacity of the blood is disturbed by decreased hemoglobin level resulting from hemodilution of the circulating blood. From the view point of the blood gas exchange, these experimental studies were undertaken to determined the sate limit of hemodilution in the condition of cardiopulmonary bypass with a constant perfusion flow rate. Twelve adult mongrel dogs weighing 10 to 13 Kg. were anesthetized with pentobarbital and then respiration was controlled with Harvard volume respirator using room air. The cardiopulmonary by pass was performed by use of Sarns heart lung machine (console 5000, 5 head and 2 roller pumps) and Travenol pediatric bubble oxygenator. The perfusion rate during bypass was maintained at a constant rate of 80 ml/min/Kg of body weight. The ratio of oxygen gas flow to blood flow was kept in 3 to 1 constantly. International hemodilution was attained by serial blood withdrawals and immediate infusion of equal volumes of diluants composed of Ringer's lactate, 5% dextrose in water and 25% mannitol solution, proportionally 60%, 30%, and 10%. Arterial and venous blood samples were obtained between 15 and 20 minutes following each hemodilution. Hematocrits and hemoglobin values, $PO_{2}$, $PCO_{2}$ and pH were measured. Oxygen and carbon dioxide contents oxygen consumption and carbon dioxide elimination were calculated groups according to different hematocrit values and the correlations were evaluated. Result were as follows. 1. the arterial $O_{2}$ tension and $O_{2}$ saturation were maintained at the physiological level irrespective of the hematocrit value. 2. The venous $O_{2}$ tension and $O_{2}$ saturation showed a tendency to decline with the decrease in hematocrit value and positive correlation between them (r = +0.49, r = +0.76), The mean values of venous $O_{2}$ tension and $O_{2}$ saturation, however, were not decreased when the hematocrit levels were lower than 20%. 3. The arterial $O_{2}$ content declined lineally in proportion to the fall of hematocrit level with a positive correlation between them (r = +0.95). 4. The venous $O_{2}$ contents were decreased gradually as the hematocrit value decreased with positive correlation between them ( r =+0.89). The trend of diminution of venous $O_{2}$ content, however, was became low according to progressive decrease of hematocrit level. 5. Systemic oxygen consumption was in higher range than $O_{2}$ requirement of basal metabolism when the hematocrit value was above 20%, but abruptly decreased when the hematocrit value became to below 20%. 6. The arterial $CO_{2}$ tension and $CO_{2}$ content showed trend of increasing with progressive decrease of hematocrit value but exhibited a rather broad range and there was no relationship between those value and the hematocrit value. 7. The venous $CO_{2}$ tension and $CO_{2}$ content have also no correlation with change of Ht. value but related directly to those value of arterial blood with positive correlation between them (r = +0.78, r = +0.95_. 8. A-V difference of $CO_{2}$ content and $CO_{2}$ elimination wasnot significantly influenced by Ht. value. From the results, we obtained that feasible limit in inteneional hemodilution is above the hematocrit value of 20% under the given experimental condition.

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A Study on Removal of NOx in Diesel Engine using Reductive Catalyst (환원촉매를 이용한 디젤엔진 배기가스 중 NOx 저감에 관한 연구)

  • Huang, H.Z.;Hwang, J.W.;Jung, J.Y.;Han, J.H.;Demidiouk, V.I.;Chae, J.O.
    • Journal of Korean Society of Environmental Engineers
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    • v.22 no.12
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    • pp.2255-2261
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    • 2000
  • To eliminate $NO_x$ in diesel emission. selective catalyst reduction (SCR) was used in real diesel engine. Among the SCR methods, metal oxide and perovskite catalysts were introduced in this paper. The removal efficiencies with various major, promoter catalysts on ${\gamma}-Al_2O_3$ at different reaction temperature were investigated, and $LaCuMnO_x$ catalyst which has high removal efficiency at the temperature of real diesel exhaust gas was selected. $NO_x$ reduction was carried out over these catalysts in the flow-through type reactor using by-pass ($SV=3,300h^{-1}$). Under the given condition to this study, perovskite catalysts showed considerably high removal efficiency and $LaCuMnO_x$ was the best one among these catalysts in the temperature range of $150{\sim}450^{\circ}C$.

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Joining and Performance of Alkali Metal Thermal-to-electric Converter (AMTEC) (알칼리금속 열전기변환장치의 접합과 출력성능)

  • Suh, Min-Soo;Lee, Wook-Hyun;Woo, Sang-Kuk
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.41 no.7
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    • pp.665-671
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    • 2017
  • The alkali-Metal Thermal-to-electric Converter (AMTEC) is one of the promising static energy conversion technologies for the direct conversion of thermal energy to electrical energy. The advantages over a conventional energy converter are its high theoretical conversion efficiency of 40% and power density of 500 W/kg. The working principle of an AMTEC battery is the electrochemical reaction of the sodium through an ion conducting electrolyte. Sodium ion pass through the hot side of the beta"-alumina solid electrolyte (BASE) primarily as a result of the pressure difference. This pressure difference across the BASE has a significant effect on the overall performance of the AMTEC system. In order to build the high pressure difference across the BASE, hermeticity is required for each joined components for high temperature range of $900^{\circ}C$. The AMTEC battery was manufactured by utilizing robust joining technology of BASE/insulator/metal flange interfaces of the system for both structural and electrical stability. The electrical potential difference between the anode and cathode sides, where the electrons emitted from sodium ionization and recombined into sodium, was characterized as the open-circuit voltage. The efforts of technological improvement were concentrated on a high-power output and conversion efficiency. This paper discusses about the joining and performance of the AMTEC systems.

Sintering Mixtures in the Stage of Establishing Chemical Equilibrium

  • Savitskii, A.P.
    • Proceedings of the Korean Powder Metallurgy Institute Conference
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    • 1999.04a
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    • pp.5-5
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    • 1999
  • The Principal deficiency of the existing notion about the sintering-mixtures consists in the fact that almost no attention is focused on the Phenomenon of alloy formation during sintering, its connection with dimensional changes of powder bodies, and no correct ideas on the driving force for the sintering process in the stage of establishing chemical equilibrium in a system are available as well. Another disadvantage of the classical sintering theory is an erroneous conception on the dissolution mechanism of solid in liquid. The two-particle model widely used in the literature to describe the sintering phenomenon in solid state disregards the nature of the neighbouring surrounding particles, the presence of pores between them, and the rise of so called arch effect. In this presentation, new basic scientific principles of the driving forces for the sintering process of a two-component powder body, of a diffusion mechanism of the interaction between solid and liquid phases, of stresses and deformation arising in the diffusion zone have been developed. The major driving force for sintering the mixture from components capable of forming solid solutions and intermetallic compounds is attributed to the alloy formation rather than the reduction of the free surface area until the chemical equilibrium is achieved in a system. The lecture considers a multiparticle model of the mixed powder-body and the nature of its volume changes during solid-state and liquid-phase sintering. It explains the discovered S-and V-type concentration dependencies of the change in the compact volume during solid-state sintering. It is supposed in the literature that the dissolution of solid in liquid is realised due to the removal of atoms from the surface of the solid phase into the melt and then their diffusicn transfer from the solid-liquid interface into the bulk of liquid. It has been shown in our experimental studies that the mechanism of the interaction between two components, one of them being liquid, consist in diffusion of the solvent atoms from the liquid into the solid phase until the concentration of solid solutions or an intermetallic compound in the surface layer enables them to pass into the liquid by means of melting. The lecture discusses peculimities of liquid phase formation in systems with intermediate compounds and the role of the liquid phase in bringing about the exothermic effect. At the frist stage of liquid phase sintering the diffusion of atoms from the melt into the solid causes the powder body to grow. At the second stage the diminution of particles in size as a result of their dissolution in the liquid draws their centres closer to each other and makes the compact to shrink Analytical equations were derived to describe quantitatively the porosity and volume changes of compacts as a result of alloy formation during liquid phase sinteIing. Selection criteria for an additive, its concentration and the temperature regime of sintering to control the density the structure of sintered alloys are given.

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IMPLICATION OF STELLAR PROPER MOTION OBSERVATIONS ON RADIO EMISSION OF SAGITTARIUS A

  • CHANG HEON-YOUNG;CHOI CHUL-SUNG
    • Journal of The Korean Astronomical Society
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    • v.36 no.3
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    • pp.81-87
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    • 2003
  • It is suggested that a flying-by star in a hot accretion disk may cool the hot accretion disk by the Comptonization of the stellar emission. Such a stellar cooling can be observed in the radio frequency regime since synchrotron luminosity depends strongly on the electron temperature of the accretion flow. If a bright star orbiting around the supermassive black hole cools the hot disk, one should expect a quasi-periodic modulation in radio, or even possible an anti-correlation of luminosities in radio and X-rays. Recently, the unprecedentedly accurate infrared imaging of the Sagittarius A$\ast$ for about ten years enables us to resolve stars around it and thus determine orbital parameters of the currently closest star S2. We explore the possibility of using such kind of observation to distinguish two quite different physical models for the central engine of the Sagittarius A$\ast$, that is, a hot accretion disk model and a jet model. We have attempted to estimate the observables using the observed parameters of the star S2. The relative difference in the electron temperature is a few parts of a thousand at the epoch when the star S2 is near at the pericenter. The relative radio luminosity difference with and without the stellar cooling is also small of order $10^{-4}$, particularly even when the star S2 is near at the pericenter. On the basis of our findings we tentatively conclude that even the currently closest pass of the star S2 is insufficiently close enough to meaningfully constrain the nature of the Sagittarius A$\ast$ and distinguish two competing models. This implies that even though Bower et al. (2002)have found no periodic radio flux variations in their data set from 1981 to 1998, which is naturally expected from the presence of a hot disk, a hot disk model cannot be conclusively ruled out. This is simply because the energy bands they have studied are too high to observe the effect of the star S2 even if it indeed interacts with the hot disk. In other words, even if there is a hot accretion disk the star like S2 has imprints in the frequency range at v $\le$ 100 MHz.

An Experimental Study on the Properties of High Flowing Concrete according to Water/Binder Ratio(W/B) (물결합재비에 따른 고유동콘크리트의 특성에 관한 실험적 연구)

  • 김무한;최세진
    • Journal of the Korea Concrete Institute
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    • v.13 no.4
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    • pp.329-335
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    • 2001
  • Recently, in many laboratories and institutes it is being studied on the high flowing concrete widely, which has high fluidity, non-segregation ability and fillingability, and sometimes being applied to the construction field actually. And the fluidity properties of high flowing concrete are influenced according to the several factors ; binder content, water/binder ratio and water content etc. This is an experimental study to compare and analyze the effect of water/binder ratio and water content on the properties of high flowing concrete. For this purpose, the mix proportion of high flowing concrete according to water/binder ratio(W/B : 0.30, 0.35, 0.40, 0.45) and water content (W : 155, 165, 175, 185 kg/㎥) was selected. And then slump-flow, V-lot, L-passing test in fresh concrete, and compressive strength, freezing and thawing test in hardened concrete were peformed. According to test results, it was found that the viscosity of all those high flowing concrete with the water content 175 kg/㎥ was satisfied with 50 cm pass time of slump flow prescribed by Japanese Architectural Standard Specification (JASS 5) - from 3 to 8 seconds. And non-segregation ability of concrete with W/B 0.35 was better than the other mix proportions. Especially, the compressive strength after curing 24 hours(1 day) of all high flowing concrete was higher than that prescribed by JASS 5(50 kgf/㎠).

The Role of Fundamentalization of Education in Improving the Future Specialists Professional Training with Usage of Multimedia Technologies

  • Palshkov, Kostiantyn;Kochubei, Olena;Tsokur, Olga;Tiahur, Vasyl;Tiahur, Liubomyra;Filimonova, Tetiana;Kuzminskyi, Anatolii
    • International Journal of Computer Science & Network Security
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    • v.22 no.9
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    • pp.95-102
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    • 2022
  • The article considers the fundamentalization of education in improving the future specialists professional training with usage of multimedia technologies by various scientists. Various points of view and approaches to defining the concepts of fundamentalization of education and multimedia technologies are identified. The concept of fundamentalization of professional training of a future specialist is based on the goals and functions of fundamentalization and - on the ways and means of achieving it, etc. Most authors agree only in their views that the fundamentalization of education is aimed at improving the quality of education and the education of the individual. Others involve the formation of a culture and worldview, increasing the creative and intellectual potential, forming the professional competence of a specialist and the potential for further education, and so on. The term multimedia refers to interactive systems that provide processing of moving and still video images, animated graphics, high-quality audio and speech. It is found out that professional training of a specialist by means of multimedia technologies includes not only the activities of the teacher and student, which form the learning process, but also the independent activity of the subject, self-development, assimilation of experience by the subject through analysis, comprehension and transformation of the field of activity in which he is included. It is revealed through the implementation of which approaches to the fundamentalization of higher professional education, it becomes possible to fully present theoretical training courses and effectively pass practical training by students, which contributes to improving the quality of training of future specialists in higher education institutions. Theoretical analysis of scientific views indicates a fairly serious attention of scientists to the problem of professional readiness of specialists and the possibility of higher educational institutions in preparing for it. At the same time, professional readiness is considered from different positions: as an active state of a person, which manifests itself in activity; as a result of activity; as goals of activity; as a quality that characterizes the attitude to solving professional problems and social situations; as a prerequisite for purposeful activity; as a form of activity of the subject; as an integral formation of personality; as a component of socio-professional culture; as a complex professionally significant neoplasm of the individual.

Evaluating efficiency of Split VMAT plan for prostate cancer radiotherapy involving pelvic lymph nodes (골반 림프선을 포함한 전립선암 치료 시 Split VMAT plan의 유용성 평가)

  • Mun, Jun Ki;Son, Sang Jun;Kim, Dae Ho;Seo, Seok Jin
    • The Journal of Korean Society for Radiation Therapy
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    • v.27 no.2
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    • pp.145-156
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    • 2015
  • Purpose : The purpose of this study is to evaluate the efficiency of Split VMAT planning(Contouring rectum divided into an upper and a lower for reduce rectum dose) compare to Conventional VMAT planning(Contouring whole rectum) for prostate cancer radiotherapy involving pelvic lymph nodes. Materials and Methods : A total of 9 cases were enrolled. Each case received radiotherapy with Split VMAT planning to the prostate involving pelvic lymph nodes. Treatment was delivered using TrueBeam STX(Varian Medical Systems, USA) and planned on Eclipse(Ver. 10.0.42, Varian, USA), PRO3(Progressive Resolution Optimizer 10.0.28), AAA(Anisotropic Analytic Algorithm Ver. 10.0.28). Lower rectum contour was defined as starting 1cm superior and ending 1cm inferior to the prostate PTV, upper rectum is a part, except lower rectum from the whole rectum. Split VMAT plan parameters consisted of 10MV coplanar $360^{\circ}$ arcs. Each arc had $30^{\circ}$ and $30^{\circ}$ collimator angle, respectively. An SIB(Simultaneous Integrated Boost) treatment prescription was employed delivering 50.4Gy to pelvic lymph nodes and 63~70Gy to the prostate in 28 fractions. $D_{mean}$ of whole rectum on Split VMAT plan was applied for DVC(Dose Volume Constraint) of the whole rectum for Conventional VMAT plan. In addition, all parameters were set to be the same of existing treatment plans. To minimize the dose difference that shows up randomly on optimizing, all plans were optimized and calculated twice respectively using a 0.2cm grid. All plans were normalized to the prostate $PTV_{100%}$ = 90% or 95%. A comparison of $D_{mean}$ of whole rectum, upperr ectum, lower rectum, and bladder, $V_{50%}$ of upper rectum, total MU and H.I.(Homogeneity Index) and C.I.(Conformity Index) of the PTV was used for technique evaluation. All Split VMAT plans were verified by gamma test with portal dosimetry using EPID. Results : Using DVH analysis, a difference between the Conventional and the Split VMAT plans was demonstrated. The Split VMAT plan demonstrated better in the $D_{mean}$ of whole rectum, Up to 134.4 cGy, at least 43.5 cGy, the average difference was 75.6 cGy and in the $D_{mean}$ of upper rectum, Up to 1113.5 cGy, at least 87.2 cGy, the average difference was 550.5 cGy and in the $D_{mean}$ of lower rectum, Up to 100.5 cGy, at least -34.6 cGy, the average difference was 34.3 cGy and in the $D_{mean}$ of bladder, Up to 271 cGy, at least -55.5 cGy, the average difference was 117.8 cGy and in $V_{50%}$ of upper rectum, Up to 63.4%, at least 3.2%, the average difference was 23.2%. There was no significant difference on H.I., and C.I. of the PTV among two plans. The Split VMAT plan is average 77 MU more than another. All IMRT verification gamma test results for the Split VMAT plan passed over 90.0% at 2 mm / 2%. Conclusion : As a result, the Split VMAT plan appeared to be more favorable in most cases than the Conventional VMAT plan for prostate cancer radiotherapy involving pelvic lymph nodes. By using the split VMAT planning technique it was possible to reduce the upper rectum dose, thus reducing whole rectal dose when compared to conventional VMAT planning. Also using the split VMAT planning technique increase the treatment efficiency.

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Edge to Edge Model and Delay Performance Evaluation for Autonomous Driving (자율 주행을 위한 Edge to Edge 모델 및 지연 성능 평가)

  • Cho, Moon Ki;Bae, Kyoung Yul
    • Journal of Intelligence and Information Systems
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    • v.27 no.1
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    • pp.191-207
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    • 2021
  • Up to this day, mobile communications have evolved rapidly over the decades, mainly focusing on speed-up to meet the growing data demands of 2G to 5G. And with the start of the 5G era, efforts are being made to provide such various services to customers, as IoT, V2X, robots, artificial intelligence, augmented virtual reality, and smart cities, which are expected to change the environment of our lives and industries as a whole. In a bid to provide those services, on top of high speed data, reduced latency and reliability are critical for real-time services. Thus, 5G has paved the way for service delivery through maximum speed of 20Gbps, a delay of 1ms, and a connecting device of 106/㎢ In particular, in intelligent traffic control systems and services using various vehicle-based Vehicle to X (V2X), such as traffic control, in addition to high-speed data speed, reduction of delay and reliability for real-time services are very important. 5G communication uses high frequencies of 3.5Ghz and 28Ghz. These high-frequency waves can go with high-speed thanks to their straightness while their short wavelength and small diffraction angle limit their reach to distance and prevent them from penetrating walls, causing restrictions on their use indoors. Therefore, under existing networks it's difficult to overcome these constraints. The underlying centralized SDN also has a limited capability in offering delay-sensitive services because communication with many nodes creates overload in its processing. Basically, SDN, which means a structure that separates signals from the control plane from packets in the data plane, requires control of the delay-related tree structure available in the event of an emergency during autonomous driving. In these scenarios, the network architecture that handles in-vehicle information is a major variable of delay. Since SDNs in general centralized structures are difficult to meet the desired delay level, studies on the optimal size of SDNs for information processing should be conducted. Thus, SDNs need to be separated on a certain scale and construct a new type of network, which can efficiently respond to dynamically changing traffic and provide high-quality, flexible services. Moreover, the structure of these networks is closely related to ultra-low latency, high confidence, and hyper-connectivity and should be based on a new form of split SDN rather than an existing centralized SDN structure, even in the case of the worst condition. And in these SDN structural networks, where automobiles pass through small 5G cells very quickly, the information change cycle, round trip delay (RTD), and the data processing time of SDN are highly correlated with the delay. Of these, RDT is not a significant factor because it has sufficient speed and less than 1 ms of delay, but the information change cycle and data processing time of SDN are factors that greatly affect the delay. Especially, in an emergency of self-driving environment linked to an ITS(Intelligent Traffic System) that requires low latency and high reliability, information should be transmitted and processed very quickly. That is a case in point where delay plays a very sensitive role. In this paper, we study the SDN architecture in emergencies during autonomous driving and conduct analysis through simulation of the correlation with the cell layer in which the vehicle should request relevant information according to the information flow. For simulation: As the Data Rate of 5G is high enough, we can assume the information for neighbor vehicle support to the car without errors. Furthermore, we assumed 5G small cells within 50 ~ 250 m in cell radius, and the maximum speed of the vehicle was considered as a 30km ~ 200 km/hour in order to examine the network architecture to minimize the delay.