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Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice

  • Jung Ah Kim;Sung-Hee Kim;Jeong Jin Kim;Hyuna Noh;Su-bin Lee;Haengdueng Jeong;Jiseon Kim;Donghun Jeon;Jung Seon Seo;Dain On;Suhyeon Yoon;Sang Gyu Lee;Youn Woo Lee;Hui Jeong Jang;In Ho Park;Jooyeon Oh;Sang-Hyuk Seok;Yu Jin Lee;Seung-Min Hong;Se-Hee An;Joon-Yong Bae;Jung-ah Choi;Seo Yeon Kim;Young Been Kim;Ji-Yeon Hwang;Hyo-Jung Lee;Hong Bin Kim;Dae Gwin Jeong;Daesub Song;Manki Song;Man-Seong Park;Kang-Seuk Choi;Jun Won Park;Jun-Won Yun;Jeon-Soo Shin;Ho-Young Lee;Ho-Keun Kwon;Jun-Young Seo;Ki Taek Nam;Heon Yung Gee;Je Kyung Seong
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.7.1-7.19
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    • 2024
  • Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×12 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

The effect of tunnel ovality on the dynamic behavior of segment lining (Ovality가 세그먼트 라이닝의 동적 거동 특성에 미치는 영향)

  • Gyeong-Ju Yi;Ki-Il Song
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.25 no.6
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    • pp.423-446
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    • 2023
  • Shield TBM tunnel linings are segmented into segments and rings. This study investigates the response characteristics of the stress and displacement of the segment lining under seismic waves through modeling that considers the interface behavior between segments by applying a shell interface element to the contact surface between segments and rings. And there is no management criteria for ovaling deformation of segment linings in Korea. So, this study the ovality criteria and meaning of segment lining. The results of study showed that the distribution patterns of stress and displacement under seismic waves were similar between continuous linings and segment linings. However, the maximum values of stress and displacement showed differences from segment linings. The stress distribution of the continuous lining modeled as a shell type has a stress distribution that has continuity in the 3D cylindrical shape, but the segment lining is concentrated outside the segment, and the largest stress occurs at the location where the contact surface between the segment and the ring is concentrated. This intermittent and localized stress distribution shows an increasing as the ovality of the lining increases at seismic waves. The ovality at which the increase in stress distribution begins to show irregularity and localization is about 150‰. Ovality of 150‰ is an unrealistic value that cannot represent actual lining deformation. Therefore, the ovality of the segment lining increase with depth, but it does not have a significant impact on the stability caused by seismic load.

CD45RA+ Depleted Lymphocyte Infusion for Treatment of Refractory Cytomegalovirus Disease in Complete DiGeorge Syndrome: A Case Report

  • HyungJin Chin;Young Hye Ryu;Da Yun Kang;Hyun Jin Park;Kyung Taek Hong ;Jung Yoon Choi;Ki Wook Yun;Bongjin Lee;Hyoung Jin Kang;Eun Hwa Choi
    • Pediatric Infection and Vaccine
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    • v.30 no.3
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    • pp.173-179
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    • 2023
  • Complete DiGeorge syndrome (cDGS) refers to DGS with profound T cell deficiency. Herein, we present the case of an infant with cDGS suffering from refractory cytomegalovirus (CMV) infection and who was treated with CD45RA+ depleted lymphocyte infusion. The patient was diagnosed with cDGS by fluorescence in situ hybridization which verified 22q11.2 deletion and as well as by the observed profound T cell deficiency (CD3+ T cells 69/μL, CD4+ T cells 7/μL). On the 45th day of age, CMV viremia was first detected with a plasma viral load (VL) of 120,000 IU/mL. Ganciclovir treatment effectively reduced VL post 56 days of treatment; however, VL subsequently rebounded. A CMV UL97 phosphotransferase M460V mutation conferring ganciclovir resistance emerged and foscarnet was incorporated. Despite this, high titers of CMV viremia (VL 2,820,000 IU/mL) and CMV retinitis were complicated. To restore T cell immunity and treat refractory CMV infection, CD45RA+ depleted CMV-specific lymphocytes from the patient's father were infused twice on the 196th and 207th days after birth. After receiving the second infusion, a decline in CMV VL was observed, with a decrease to 87,100 IU/mL by the tenth day following infusion, despite the failure in maintaining T cell increase. The patient died of Pneumocystis jirovecii pneumonia and Elizabethkingia meningoseptica sepsis on the 222nd day after birth. CD45RA+ depleted lymphocyte infusion may be a therapeutic option for refractory CMV disease in cDGS patients.

Analysis on dynamic numerical model of subsea railway tunnel considering various ground and seismic conditions (다양한 지반 및 지진하중 조건을 고려한 해저철도 터널의 동적 수치모델 분석)

  • Changwon Kwak;Jeongjun Park;Mintaek Yoo
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.25 no.6
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    • pp.583-603
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    • 2023
  • Recently, the advancement of mechanical tunnel boring machine (TBM) technology and the characteristics of subsea railway tunnels subjected to hydrostatic pressure have led to the widespread application of shield TBM methods in the design and construction of subsea railway tunnels. Subsea railway tunnels are exposed in a constant pore water pressure and are influenced by the amplification of seismic waves during earthquake. In particular, seismic loads acting on subsea railway tunnels under various ground conditions such as soft ground, soft soil-rock composite ground, and fractured zones can cause significant changes in tunnel displacement and stress, thereby affecting tunnel safety. Additionally, the dynamic response of the ground and tunnel varies based on seismic load parameters such as frequency characteristics, seismic waveform, and peak acceleration, adding complexity to the behavior of the ground-tunnel structure system. In this study, a finite difference method is employed to model the entire ground-tunnel structure system, considering hydrostatic pressure, for the investigation of dynamic behavior of subsea railway tunnel during earthquake. Since the key factors influencing the dynamic behavior during seismic events are ground conditions and seismic waves, six analysis cases are established based on virtual ground conditions: Case-1 with weathered soil, Case-2 with hard rock, Case-3 with a composite ground of soil and hard rock in the tunnel longitudinal direction, Case-4 with the tunnel passing through a narrow fault zone, Case-5 with a composite ground of soft soil and hard rock in the tunnel longitudinal direction, and Case-6 with the tunnel passing through a wide fractured zone. As a result, horizontal displacements due to earthquakes tend to increase with an increase in ground stiffness, however, the displacements tend to be restrained due to the confining effects of the ground and the rigid shield segments. On the contrary, peak compressive stress of segment significantly increases with weaker ground stiffness and the effects of displacement restrain contribute the increase of peak compressive stress of segment.

Shear strain behaviour due to twin tunnelling adjacent to pile group (군말뚝 기초 하부 병렬터널 굴착 시 전단변형 거동 특성)

  • Subin Kim;Young-Seok Oh;Yong-Joo Lee
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.26 no.1
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    • pp.59-78
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    • 2024
  • In tunnel construction, the stability is evaluated by the settlement of adjacent structures and ground, but the shear strain of the ground is the main factor that determines the failure mechanism of the ground due to the tunnel excavation and the change of the operating load, and can be used to review the stability of the tunnel excavation and to calculate the reinforcement area. In this study, a twin tunnel excavation was simulated on a soft ground in an urban area through a laboratory model test to analyze the behavior of the twin tunnel excavation on the adjacent pile grouped foundation and adjacent ground. Both the displacement and the shear strain of ground were obtained using a close-range photogrammetry during laboratory model test. In addition, two-dimensional finite element numerical analysis was performed based on the model test. The results of a back-analysis showed that the maximum shear strain rate tends to decrease as the horizontal distance between the pillars of the twin tunnel and the vertical distance between the toe of the pile group and the crown of the tunnel were decreased. The impact of the second tunnel on the first tunnel and pile group was decreased as the horizontal distance between the pillars of the twin tunnel was increased. In addition, the vertical distance between the toe of the pile group and the crown of the tunnel had a relatively greater impact on the shear strain results than the horizontal distance of the pillars between the twin tunnels. According to the results of the close-range photogrammetry and numerical analysis, the settlement of adjacent pile group and adjacent ground was measured within the design criteria, but the shear strain of the ground was judged to be outside the range of small strain in all cases and required reinforcement.

Comparison of In Vitro, Ex Vivo, and In Vivo Antibacterial Activity Test Methods for Hand Hygiene Products (손 위생 제품에 대한 in vitro, ex vivo, in vivo 항균 시험법 비교)

  • Daeun Lee;Hyeonju Yeo;Haeyoon Jeong
    • Journal of Food Hygiene and Safety
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    • v.39 no.1
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    • pp.35-43
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    • 2024
  • Numerous methods have been applied to assess the antibacterial effectiveness of hand hygiene products. However, the different results obtained through various evaluation methods have complicated our understanding of the real efficacy of the products. Few studies have compared test methods for assessing the efficacy of hand hygiene products. In particular, reports on ex vivo pig skin testing are limited. This study aimed to compare and characterize the methodologies applied for evaluating hand hygiene products, involving in vitro, ex vivo, and in vivo approaches, applicable to both leave-on sanitizers and wash-off products. Our further aim was to enhance the reliability of ex vivo test protocols by identifying influential factors. We performed an in vitro method (EN1276) and an in vivo test (EN1499 and ASTM2755) with at least 20 participants, against Serratia marcescens or Escherichia coli and Staphylococcus aureus. For the ex vivo experiment, we used pig skin squares prepared in the same way as those used in the in vivo test method and determined the optimal treated sample volumes for sanitizers and the amount of water required to wash off the product. The hand sanitizers showed at least a 5-log reduction in bacterial load in the in vitro test, while they showed little antibacterial activity in the in vivo and ex vivo tests, particularly those with a low alcohol content. For the hand wash products, the in vitro test was limited because of bubble formation or the high viscosity of the products and it showed low antibacterial activity of less than a 1-log reduction against E. coli. In contrast, significantly higher log reductions were observed in ex vivo and in vivo tests, consistently demonstrating these results across the two methods. Our findings revealed that the ex vivo and in vivo tests reflect the two different antibacterial mechanisms of leave-on and wash-off products. Our proposed optimized ex vivo test was more rapid and more precise than the in vitro test to evaluate antibacterial results.

The continuous application effect of the food waste composts on the cultivated upland soils and plants (밭에서 음식물류폐기물 활용 퇴비의 연용이 토양 및 작물에 미치는 영향)

  • Kwon, Soon-Ik;So, Kyu-Ho;Hong, Seung-Gil;Kim, Gun-Yeob;Seong, Ki-Seog;Park, Woo-Kyun;Kim, Kwon-Rae;Lee, Deog-Bae;Jung, Kwang-Yong
    • Journal of the Korea Organic Resources Recycling Association
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    • v.17 no.3
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    • pp.71-81
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    • 2009
  • Food waste has been actively used as a composting material in order to reduce the environmental pollution load and to enhance the recycling of resources. In this study, the longterm effects of continuous application of food waste compost to soils on both the crop production and the soil properties were examined to ensure the safety of food waste compost in agricultural use. In addition, we collected the preliminary data for establishing standard application rate of food waste compost for agricultural utilization. Based on conventional nitrogen application rate of chemical fertilizer for crop cultivation, pig manure compost $(24g\;N\;kg^{-1}$, $8g\;P_2O_5\;kg^{-1}$, and $10.4g\;K_2O\;kg^{-1})$ and food waste compost ($20g\;N\;kg^{-1}$, $20.1g\;P_2O_5\;kg^{-1}$, and $6.5g\;K_2O\;kg^{-1}$) were applied to the upland soil in $2{\times}2{\times}2m$ lysimeter in which lettuce (Lactuca sativa var. crispa), Chinese cabbage (Brassica campestris subsp. napus var. pekinensis), red pepper (Capsicum annuum), and potato (Solanum tuberosum) were grown continuously. The crops grown in soils to which food waste compost applied showed better growth responses than the control, whereas some variations were observed in the crops grown in chemical fertilizer treated soils. Continuous application of food waste compost increased the contents of organic matter, nitrogen, and phosphorus, which resulted in improving soil aeration.

Characteristics of Pyrophyllite Powder Molding Material by High-Speed, High-Pressure Dynamic Compression Technology (고속고압 동적 압축 기술에 의한 연납석 분말 성형 재료 특성)

  • Jeongdu Noh;Sangyeon Ban;Taeyoon Oh;Jangbok Wi;Seong-Seung Kang
    • The Journal of Engineering Geology
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    • v.34 no.3
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    • pp.403-413
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    • 2024
  • This study aims to investigate the material properties of specimens made from pyrophyllite and pyrophyllite-aluminum mixed powders using high-speed, high-pressure dynamic compression technology. The aluminum powder exhibited a highly uniform particle size distribution ranging from 10 to 100 ㎛, whereas the pyrophyllite powder displayed four distinct particle size distributions: 0.1~1 ㎛, 1~10 ㎛, 80~100 ㎛, and 200~1,000 ㎛. Using high-speed, high-pressure dynamic compression technology with a drop time of approximately 0.34~0.4 seconds and a dynamic load of about 207 tonf, it was possible to fabricate pyrophyllite and pyrophyllite-aluminum mixed powder specimens with a volume of about 548 mm2. The Shore hardness measurement results showed that specimen BG100 had an average of 43.7, BG90 had an average of 33.2, and BG85, BG80, BG75, and BG70 had an average of 31.0, indicating that the specimen with the least aluminum content exhibited the highest Shore hardness value. The thermogravimetric analysis revealed mass losses at two points: the first mass loss occurred at around 270℃ with a loss of approximately 1.45%, and the second mass loss occurred at around 600℃, where BG70 and BG80 showed a mass loss of about 2.53%, and BG75, BG85, and BG90 showed a mass loss of about 3.43%. Scanning electron microscopy analysis indicated that the microstructure of the specimens was similar regardless of the mixing ratio, with three elements-O, Si, and Al-being detected in all specimens. The mapping analysis of BG90 revealed an oxygen weight ratio of 50.80%, silicon weight ratio of 37.36%, and aluminum weight ratio of 11.85%. In the case of BG85, the results were 43.09% oxygen, 43.50% silicon, and 13.41% aluminum; for BG80, the results were 44.83% oxygen, 40.30% silicon, and 14.87% aluminum; for BG75, the results were 44.71% oxygen, 35.49% silicon, and 19.80% aluminum; and for BG70, the results were 34.95% oxygen, 35.73% silicon, and 29.32% aluminum.

Cardio-pulmonary Adaptation to Physical Training (운동훈련(運動訓練)에 대(對)한 심폐기능(心肺機能)의 적응(適應)에 관(關)한 연구(硏究))

  • Cho, Kang-Ha
    • The Korean Journal of Physiology
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    • v.1 no.1
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    • pp.103-120
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    • 1967
  • As pointed out by many previous investigators, the cardio-pulmonary system of well trained athletes is so adapted that they can perform a given physical exercise more efficiently as compared to non-trained persons. However, the time course of the development of these cardio-pulmonary adaptations has not been extensively studied in the past. Although the development of these training effects is undoubtedly related to the magnitude of an exercise load which is repeatedly given, it would be practical if one could maintain a good physical fitness with a minimal daily exercise. Hence, the present investigation was undertaken to study the time course of the development of cardio-pulmonary adaptations while a group of non-athletes was subjected to a daily 6 to 10 minutes running exercise for a period of 4 weeks. Six healthy male medical students (22 to 24 years old) were randomly selected as experimental subjects, and were equally divided into two groups (A and B). Both groups were subjected to the same daily running exercise (approximately 1,000 kg-m). 6 days a week for 4 weeks, but the rate of exercise was such that the group A ran on treadmill with 8.6% grade for 10 min daily at a speed of 127 m/min while the group B ran for 6 min at a speed of 200 m/min. In order to assess the effects of these physical trainings on the cardio-pulmonary system, the minute volume, the $O_2$ consumption, the $CO_2$ output and the heart rate were determined weekly while the subject was engaged in a given running exercise on treadmill (8.6% grade and 127 m/min) for a period of 5 min. In addition, the arterial blood pressure, the cardiac output, the acid-base state of arterial blood and the gas composition of arterial blood were also determined every other week in 4 subjects (2 from each group) while they were engaged in exercise on a bicycle ergometer at a rate of approximately 900 kg m/min until exhaustion. The maximal work capacity was also determined by asking the subject to engage in exercise on treadmill and ergometer until exhaustion. For the measurement of minute volume, the expired gas was collected in a Douglas bag. The $O_2$ consumption and the $CO_2$ output were subsequently computed by analysing the expired gas with a Scholander micro gas analyzer. The heart rate was calculated from the R-R interval of ECG tracings recorded by an Offner RS Dynograph. A 19 gauge Cournand needle was inserted into a brachial artery, through which arterial blood samples were taken. A Statham $P_{23}AA$ pressure transducer and a PR-7 Research Recorder were used for recording instantaneous arterial pressure. The cardiac output was measured by indicator (Cardiogreen) dilution method. The results may be summarized as follows: (1) The maximal running time on treadmill increased linearly during the 4 week training period at the end of which it increased by 2.8 to 4.6 times. In general, an increase in the maximal running time was greater when the speed was fixed at a level at which the subject was trained. The mammal exercise time on bicycle ergometer also increased linearly during the training period. (2) In carrying out a given running exercise on treadmill (8.6%grade, 127 m/min), the following changes in cardio·pulmonary functions were observed during the training period: (a) The minute volume as well as the $O_2$ consumption during steady state exercise tended to decrease progressively and showed significant reductions after 3 weeks of training. (b) The $CO_2$ production during steady state exercise showed a significant reduction within 1 week of training. (c) The heart rate during steady state exercise tended to decrease progressively and showed a significant reduction after 2 weeks of training. The reduction of heart rate following a given exercise tended to become faster by training and showed a significant change after 3 weeks. Although the resting heart rate also tended to decrease by training, no significant change was observed. (3) In rallying out a given exercise (900 kg-m/min) on a bicycle ergometer, the following change in cardio-vascular functions were observed during the training period: (3) The systolic blood pressure during steady state exercise was not affected while the diastolic blood Pressure was significantly lowered after 4 weeks of training. The resting diastolic pressure was also significantly lowered by the end of 4 weeks. (b) The cardiac output and the stroke volume during steady state exercise increased maximally within 2 weeks of training. However, the resting cardiac output was not altered while the resting stroke volume tended to increase somewhat by training. (c) The total peripheral resistance during steady state exercise was greatly lowered within 2 weeks of training. The mean circulation time during exorcise was also considerably shortened while the left heart work output during exercise increased significantly within 2 weeks. However, these functions_at rest were not altered by training. (d) Although both pH, $P_{co2}\;and\;(HCO_3-)$ of arterial plasma decreased during exercise, the magnitude of reductions became less by training. On the other hand, the $O_2$ content of arterial blood decreased during exercise before training while it tended to increase slightly after training. There was no significant alteration in these values at rest. These results indicate that cardio-pulmonary adaptations to physical training can be acquired by subjecting non-athletes to brief daily exercise routine for certain period of time. Although the time of appearance of various adaptive phenomena is not identical, it may be stated that one has to engage in daily exercise routine for at least 2 weeks for the development of significant adaptive changes.

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Mechanical Characteristics of the Rift, Grain and Hardway Planes in Jurassic Granites, Korea (쥬라기 화강암류에서 발달된 1번 면, 2번 면 및 3번 면의 역학적 특성)

  • Park, Deok-Won
    • Korean Journal of Mineralogy and Petrology
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    • v.33 no.3
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    • pp.273-291
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    • 2020
  • The strength characteristics of the three orthogonal splitting planes, known as rift, grain and hardway planes in granite quarries, were examined. R, G and H specimens were obtained from the block samples of Jurassic granites in Geochang and Hapcheon areas. The directions of the long axes of these three specimens are perpendicular to each of the three planes. First, The chart, showing the scaling characteristics of three graphs related to the uniaxial compressive strengths of R, G and H specimens, were made. The graphs for the three specimens, along with the increase of strength, are arranged in the order of H < G < R. The angles of inclination of the graphs for the three specimens, suggesting the degree of uniformity of the texture within the specimen, were compared. The above angles for H specimens(θH, 24.0°~37.3°) are the lowest among the three specimens. Second, the scaling characteristics related to the three graphs of RG, GH and RH specimens, representing a combination of the mean compressive strengths of the two specimens, were derived. These three graphs, taking the various N-shaped forms, are arranged in the order of GH < RH < RG. Third, the correlation chart between the strength difference(Δσt) and the angle of inclination(θ) was made. The above two parameters show the correlation of the exponential function with an exponent(λ) of -0.003. In both granites, the angle of inclination(θRH) of the RH-graph is the lowest. Fourth, the six types of charts, showing the correlations among the three kinds of compressive strengths for the three specimens and the five parameters for the two sets of microcracks aligned parallel to the compressive load applied to each specimen, were made. From these charts for Geochang and Hapcheon granites, the mean value(0.877) of the correlation coefficients(R2) for total density(Lt), along with the frequency(N, 0.872) and density(ρ, 0.874), is the highest. In addition, the mean values(0.829) of correlation coefficients associated with the mean compressive strengths are more higher than the minimum(0.768) and maximum(0.804) compression strengths of three specimens. Fifth, the distributional characteristics of the Brazilian tensile strengths measured in directions parallel to the above two sets of microcracks in the three specimens from Geochang granite were derived. From the related chart, the three graphs for these tensile strengths corresponding to the R, G and H specimens show an order of H(R1+G1) < G(R2+H1) < R(R1+G1). The order of arrangement of the three graphs for the tensile strengths and that for the compressive strengths are mutually consistent. Therefore, the compressive strengths of the three specimens are proportional to the three types of tensile strengths. Sixth, the values of correlation coefficients, among the three tensile strengths corresponding to each cumulative number(N=1~10) from the above three graphs and the five parameters corresponding to each graph, were derived. The mean values of correlation coefficients for each parameter from the 10 correlation charts increase in the order of density(0.763) < total length(0.817) < frequency(0.839) < mean length(Lm, 0.901) ≤ median length(Lmed, 0.903). Seventh, the correlation charts among the compressive strengths and tensile strengths for the three specimens were made. The above correlation charts were divided into nine types based on the three kinds of compressive strengths and the five groups(A~E) of tensile strengths. From the related charts, as the tensile strength increases with the mean and maximum compressive strengths excluding the minimum compressive strength, the value of correlation coefficient increases rapidly.