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Current and Future Perspectives of Lung Organoid and Lung-on-chip in Biomedical and Pharmaceutical Applications

  • Junhyoung Lee;Jimin Park;Sanghun Kim;Esther Han;Sungho Maeng;Jiyou Han
    • Journal of Life Science
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    • v.34 no.5
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    • pp.339-355
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    • 2024
  • The pulmonary system is a highly complex system that can only be understood by integrating its functional and structural aspects. Hence, in vivo animal models are generally used for pathological studies of pulmonary diseases and the evaluation of inhalation toxicity. However, to reduce the number of animals used in experimentation and with the consideration of animal welfare, alternative methods have been extensively developed. Notably, the Organization for Economic Co-operation and Development (OECD) and the United States Environmental Protection Agency (USEPA) have agreed to prohibit animal testing after 2030. Therefore, the latest advances in biotechnology are revolutionizing the approach to developing in vitro inhalation models. For example, lung organ-on-a-chip (OoC) and organoid models have been intensively studied alongside advancements in three-dimensional (3D) bioprinting and microfluidic systems. These modeling systems can more precisely imitate the complex biological environment compared to traditional in vivo animal experiments. This review paper addresses multiple aspects of the recent in vitro modeling systems of lung OoC and organoids. It includes discussions on the use of endothelial cells, epithelial cells, and fibroblasts composed of lung alveoli generated from pluripotent stem cells or cancer cells. Moreover, it covers lung air-liquid interface (ALI) systems, transwell membrane materials, and in silico models using artificial intelligence (AI) for the establishment and evaluation of in vitro pulmonary systems.

The Evaluation of the Packaging Properties and Recyclability with Modified Acrylic Emulsion for Flexible Food Paper Coating (유연 종이 식품 포장재의 개질 아크릴 에멀젼 코팅 특성 및 재활용성 평가)

  • Myungho Lee;In Seok Cho;Dong Cheol Lee;Youn Suk Lee
    • KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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    • v.29 no.3
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    • pp.153-161
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    • 2023
  • The worldwide effects of COVID-19 have led to a surge in online shopping and contactless services. The consumption pattern has caused the issues such as the environmental pollution together with the increase of plastic waste. Reducing the reliance on the petroleum based plastic use for the package and replacing it with environmentally friendly material are the simple ways in order to solve those problems. Paper is an eco-friendly product with high recyclability as the food packaging materials but has still poor barrier properties. A barrier coating on surface of the paper can be achieved with the proper packaging materials featuring water, gas and grease barrier. Polyethylene (PE) or polypropylene (PP) coatings which are generally laminated or coated to paper are widely used in food packaging applications to protect products from moisture and provide water or grease resistance. However, recycling of packaging containing PE or PP matrix is limited and costly because those films are difficult to degrade in the environment. This study investigated the recyclability of modified acrylic emulsion coating papers compared to PE and PP polymer matrixes as well as their mechanical and gas barrier properties. The results showed that PE or modified acrylic emulsion coated papers had better mechanical properties compared to the uncoated paper as a control. PE or PP coating papers showed strong oil resistance property, achieving a kit rating of 12. Those papers also had a significantly higher percentage of screen reject during the recycling process than modified acrylic coated paper which had a screen rejection rate of 6.25%. In addition an uncoated paper had similar value of a screen rejection rate. It may suggest that modified acrylic emulsion coating paper can be more easily recycled than PE or PP coating papers. The overall results of the study found that modified acrylic emulsion coating paper would be a viable alternative to suggest a possible solution to an environmental problem as well as enhancing the weak mechanical and poor gas barrier properties of the paper against moisture.

Chest CT Findings of COVID-19 Patients with Mild Clinical Symptoms at a Single Hospital in Korea (경증의 임상 소견을 보이는 COVID-19 환자들의 흉부 CT 소견)

  • Woon Young Baek;Young Kyung Lee;Suhyun Kim;Chorom Hahm;Mi Young Ahn;Dong Hyun Oh;Jae-Phil Choi
    • Journal of the Korean Society of Radiology
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    • v.82 no.1
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    • pp.139-151
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    • 2021
  • Purpose To retrospectively evaluate the chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) in patients with mild clinical symptoms at a single hospital in South Korea. Materials and Methods CT scans of 87 COVID-19 patients [43 men and 44 women; median age: 41 years (interquartile range: 26.1-51.0 years)] with mild clinical symptoms (fever < 38℃ and no dyspnea) were evaluated. Results CT findings were normal in 39 (44.8%) and abnormal in 48 (55.2%) patients. Among the 48 patients with lung opacities, 17 (35.4%) had unilateral disease and 31 (64.6%) had bilateral disease. One (2.1%) patient showed subpleural distribution, 9 (18.8%) showed peribronchovascular distribution, and 38 (79.2%) showed subpleural and peribronchovascular distributions. Twenty-two (45.8%) patients had pure ground-glass opacities (GGOs) with no consolidation, 17 (35.4%) had mixed opacities dominated by GGOs, and 9 (18.8%) had mixed opacities dominated by consolidation. No patients demonstrated consolidation without GGOs. Conclusion The most common CT finding of COVID-19 in patients with mild clinical symptoms was bilateral multiple GGO-dominant lesions with subpleural and peribronchovascular distribution and lower lung predilection. The initial chest CT of almost half of COVID-19 patients with mild clinical symptoms showed no lung parenchymal lesions. Compared to relatively severe cases, mild cases were more likely to manifest as unilateral disease with pure GGOs or GGO-dominant mixed opacities and less likely to show air bronchogram.

Diagnostic Approach to the Solitary Pulmonary Nodule : Reappraisal of the Traditional Clinical Parameters for Differentiating Malignant Nodule from Benign Nodule (고립성 폐결절에 대한 진단적 접근 : 악성결절과 양성결절의 감별 지표에 대한 재검토)

  • Kho, Won Jung;Kim, Cheol Hyeon;Jang, Seung Hun;Lee, Jae Ho;Yoo, Chul Gyu;Chung, Hee Soon;Kim, Young Whan;Han, Sung Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.500-518
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    • 1996
  • Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patient. Many clinical characteristics(i.e. age, smoking history, prior history of malignancy) and radiological characteristics( i.e. size, calcification, growth rate, several findings of computed tomography) have been proposed to help to determine whether the SPN was benign or malignant. However, most of these diagnostic guidelines are based on the data collected before computed tomography(CT) has been introduced and lung cancer was not as common as these days. Moreover, it is not well established whether these guidelines from western populations could be applicable to Korean patients. Methods : We had a retrospective analysis of the case records and radiographic findings in 114 patients presenting with SPN from Jan. 1994 to Feb. 1995 in Seoul National University Hospital, a tertiary referral hospital. Results : We observed the following results ; (1) Out of 113 SPNs, the etiology was documented in 94 SP IS. There were 34 benign SP s and 60 malignant SPNs. Among which, 49 SPNs were primary lung cancers and the most common hi stologic type was adenocarcinoma. (2) The average age of patients with benign and malignant SPNs was $49.7{\pm}12.0$ and $58.1{\pm}10.0$ years, respectively( p=0.0004), and the malignant SPNs had a striking linear propensity to increase with age. (3) No significant difference in the hi story of smoking was noted between the patients with benign SPNs($13.0{\pm}17.6$ pack- year) and those with malignant SPNs($18.6{\pm}25.1$ pack-year) (p=0.2108). (4) 9 out of 10 patients with prior history of malignancy had malignant SPNs. 5 were new primary lung cancers with no relation to prior malignancy. (5) The average size of benign SPNs($3.01{\pm}1.20cm$) and malignant SPNs($2.98{\pm}0.97cm$) was not significantly different(p=0.8937). (6) The volume doubling time could be calculated in 22 SPNs. 9 SPNs had the volume doubling time longer than 400 days. Out of these, 6 were malignant SPNs. (7) The CT findings suggesting malignancy included the lobulated or spiculated border, air- bronchogram, pleural tail, and lymphadenopathy. In contrast, calcification, central low attenuation, cavity with even thickness, well-marginated border, and peri nodular micronodules were more suggestive for benign nodule. (8) The diagnostic yield of percutaneous needle aspiration and biopsy was 57.6%(19/33) of benign SPNs and 81.0%(47/58) of malignant SPNs. The diagnostic value of sputum analysis and bronchoscopic evaluations were relatively very low. (9) 42.3%(11/26) of SPNs of undetermined etiology preoperatively turned out to be malignant after surgical resection. Overall, 75.4%(46/61) of surgically resected SPNs were malignant. Conclusions : We conclude that the likelihood of malignant SPN correlates the age of patient, prior history of malignancy, some CT findings including lobulated or spiculated border, air-bronchogram, pleural tail and lymphadenopathy. However, the history of smoking, the size of the nodule, and the volume doubling time are not helpful to determent whether the SPN is benign or malignant, which have been regarded as valuable clinical parameters previously. We suggest that aggressive diagnostic approach including surgical resection is necessary in patient with SPNs.

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Experimental Study of Flip-Bucket Type Hydraulic Energy Dissipator on Steep slope Channel (긴구배수로 감세공의 Filp Bucket형 이용연구)

  • 김영배
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.13 no.1
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    • pp.2206-2217
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    • 1971
  • Spillway and discharge channel of reservoirs require the Control of Large volume of water under high pressure. The energies at the downstream end of spillway or discharge channel are tremendous. Therefore, Some means of expending the energy of the high-velocity flow is required to prevent scour of the riverbed, minimize erosion, and prevent undermining structures or dam it self. This may be accomplished by Constructing an energy dissipator at the downstream end of spillway or discharge channel disigned to dissipated the excessive energy and establish safe flow Condition in the outlet channel. There are many types of energy dissipators, stilling basins are the most familar energy dissipator. In the stilling basin, most energies are dissipated by hydraulic jump. stilling basins have some length to cover hydraulic jump length. So stilling basins require much concrete works and high construction cost. Flip bucket type energy dissipators require less construction cost. If the streambed is composed of firm rock and it is certain that the scour will not progress upstream to the extent that the safety of the structure might be endangered, flip backet type energy dissipators are the most recommendable one. Following items are tested and studied with bucket radius, $R=7h_2$,(medium of $4h_2{\geqq}R{\geqq}10h_2$). 1. Allowable upstream channel slop of bucket. 2. Adequate bucket lip angle for good performance of flip bucket. Also followings are reviwed. 1. Scour by jet flow. 2. Negative pressure distribution and air movement below nappe flow. From the test and study, following results were obtained. 1. Upstream channel slope of bucket (S=H/L) should be 0.25<H/L<0.75 for good performance of flip bucket. 2. Adequated lip angle $30^{\circ}{\sim}40^{\circ}$ are more reliable than $20^{\circ}{\sim}30^{\circ}$ for the safety of structures.

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Preparation of Powdered Smoked-Dried Mackerel Soup and Its Taste Compounds (고등어분말수우프의 제조 및 정미성분에 관한 연구)

  • LEE Eung-Ho;OH Kwang-Soo;AHN Chang-Bum;CHUNG Bu-Gil;BAE You-Kyung;HA Jin-Hwan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.20 no.1
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    • pp.41-51
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    • 1987
  • This study was carried out to prepare powdered smoked-dried mackerel which can be used as a soup base, and to examine storage stability and the taste compounds of Products. Raw mackerel are filleted, toiled for 10 minutes and pressed to remove lipids, and then soaked in extract solution of skipjack meat. This soaked mackerel are smoked 3 times to $10-12\%$ moisture content at $80^{\circ}C$ for 8 hours. And the smoked-dried mackerel were pulverized to 50 mesh. Finally, the powdered smoked-dried mackerel were packed in a laminated film $bag(PET/Al\;foil/CPP:\;5{\mu}m/15{\mu}m/70{\mu}m,\;15\times17cm)$ with air(product C), nitrogen(product N) and oxygen absorber(product O), and then stored at room temperature for 100 days. The moisture and crude lipid content of powdered smoked-dried mackerel was $11.3-12.3\%,\;12\%$, respectively, and water activity is 0.52-0.56. And these values showed little changes during storage. The pH, VBN and amino nitrogen content increased slowly during storage. Hydrophilic and lipophilic brown pigment formation showed a tendency of increase in product(C) and showed little change in product(N) and (O). The TBA value, peroxide value and carbonyl value of product(N) and (O) were lower than those of product (C). The major fatty acids of products were 16:0, 18:1, 22:6, 18:0 and 20:5, and polyenoic acids decreased, while saturated and monoenoic acids increased during processing and storage of products. The IMP content in products were 420.2-454.2 mg/100 g and decreased slightly with storage period. And major non-volatile organic acids in products were lactic acid, succinic acid and $\alpha-ketoglutaric$ acid. In free amino acids and related compounds, major ones are histidine, alanine, hydroxyproline, lysine, glutamic acid and anserine, which occupied $80.8\%$ of total free amino acids. The taste compounds of powdered smoked-dried mackerel were free amino acids and related compounds (1,279.4 mg/100 g), non-volatile organic acids(948.1 mg/100 g), nucleotides and their related compounds (672.8 mg/100 g), total creatinine(430.4 ntg/100 g), tetaine(86.6 mg/100 g) and small amount of TMAO. The extraction condition of powdered smoked-dried mackerel in preparing soup stock is appropriate at $100^{\circ}C$ for 1 minute. Judging from the results of taste and sensory evaluation, it is concluded that the powdered smoked-dried mackerel can be used as natural flavoring substance in preparing soups and broth.

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Effect of Nasal Continuous Positive Airway Pressure after Early Surfactant Therapy in Moderate Respiratory Distress Syndrome (중등도 신생아 호흡 곤란 증후군에서 폐 표면 활성제 조기 투여 후 Nasal CPAP의 치료 효과)

  • Kim, Eun Ji;Kim, Hae Sook;Hur, Man Hoe;Lee, Sang Geel
    • Clinical and Experimental Pediatrics
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    • v.45 no.10
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    • pp.1204-1212
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    • 2002
  • Purpose : Early surfactant therapy with either gentle ventilation, high-frequency ventilation or aggressive weaning of mechanical ventilation are principles for the treatment of respiratory distress syndrome(RDS). We studied to determine the accessibility of noninvasive nasal continuous positive airway pressure(CPAP) rather than mechanical ventilation by invasive intubation after early surfactant therapy. Methods : The study group consisted of 14 infants who were born and diagnosed with moderate respiratory distress syndrome and received early surfactant therapy with nasal CPAP of PEEP 5-6 cm $H_2O$ within two hours after birth in the Fatima neonatal intensive care unit for two years from January 1999 to August 2001. The control group consisted of 15 infants who were diagnosed with the disease and could be weaned from mechanical ventilator within five days after birth during the same period. Results : The characteristics, the severity of clinical symptoms and laboratory findings in the two groups at birth showed no significant difference. Neither did the interim analysis of laboratory data in two groups. Of 14 infants in the study group who received nasal CPAP after early surfactant therapy, only two infants showed weaning failure with this therapy. In the response cases, duration of CPAP was five days and mean airway pressure was $5.4{\pm}0.5cm$ $H_2O$. Two had the complication of CPAP with abdominal distension. Final complications and outcomes in the two groups showed no signifcant difference(P>0.05). Conclusion : The clinical courses in the two groups showed no significant difference. Therefore, we suggest that early surfactant therapy with noninvasive nasal CPAP is a simple and safe method rather than aggressive weaning after invasive mechanical ventilation in moderate respiratory distress syndrome.

Results of Bronchial Sleeve Resection for Primary Lung Cancer (원발성 폐암에 대한 기관지 소매 절제술의 성적)

  • Kim, Dae-Hyun;Youn, Hyo-Chul;Kim, Soo-Cheol;Kim, Bum-Shik;Cho, Kyu-Seok;Kwak, Young-Tae;Hwang, En-Gu;Kim, Dong-Won;Park, Joo-Chul
    • Journal of Chest Surgery
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    • v.40 no.1 s.270
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    • pp.37-44
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    • 2007
  • Background: It is known that long-term survival rate in patients underwent bronchial sleeve lobectomy for primary lung cancer is at least equal to that in patients underwent pneumonectomy, and bronchial sleeve lobectomy is performed in patients with suitable tumor location even in patients have adequate pulmonary function. Sleeve pneumonectomy is performed when carina was invaded by tumor or tumor location was near to the carina. We performed this study to know our results of sleeve resection for primary lung cancer. Material and Method: We analyzed retrospectively the medical records of 45 patients who underwent sleeve lobectomy or sleeve pneumonectomy for primary lung cancer by one thoracic surgeon from May 1990 to July 2003 in Department of Thoracic & Cardiovascular Surgery, College of Medicine, Kyung Hee University. Follow-up loss was absent and last follow-up was performed in April 5, 2005. Kaplan-Meyer method and log-lank test were used to know long-term survival rate and p-value. Result: Mean age was 60 years old and male to female ratio 41:1. Histologic types were squamous cell carcinoma were 39, adenocarcinoma were 4, and others were 2 patients. Pathologic stages were I 14, II 14, and III 17 patients. Nodal stages were N0 23, N1 13, and N2 9 patients. Types of operation were sleeve lobectomy 40 and sleeve pneumonectomy 5 patients. Operative mortality was 3 patients and its cause was respiratory complications. Early complications were pneumonia 4, atelectasis 8, air leakage more than 7 days 6, and atrial fibrillation 4 patients. In 19 patients tumor was recurred. Local recurrence was 10 and systemic metastasis was 9 patients. Overall 5, 10-year survival rate were 54.2%, 42.5%. The 5, 10-year survival rates according to the pathologic stage were 83.9%, 67.1% in stage I, 55%, 47.1% in II, 33.3%, 25% in III, and significance difference was present between stage I and III. The 5, 10-year survival rate according to the lymph node involvement were 63.9%, 54.6% in N0, 53,8%, 46.5% in N1, 28.5%, 14.2% in N2, and significance difference was present between N0 and N2. Conclusion: Because bronchial sleeve lobectomy for primary lung cancer could be performed safely and shows acceptable long-term survival rate, it could be considered primary in case of suitable tumor location if complete resection is possible. Although sleeve pneumonectomy for primary lung cancer shows somewhat high operative mortality rate, it could be considered in view of curative treatment.

무령왕릉보존에 있어서의 지질공학적 고찰

  • 서만철;최석원;구민호
    • Proceedings of the KSEEG Conference
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    • 2001.05b
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    • pp.42-63
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    • 2001
  • The detail survey on the Songsanri tomb site including the Muryong royal tomb was carried out during the period from May 1 , 1996 to April 30, 1997. A quantitative analysis was tried to find changes of tomb itself since the excavation. Main subjects of the survey are to find out the cause of infiltration of rain water and groundwater into the tomb and the tomb site, monitoring of the movement of tomb structure and safety, removal method of the algae inside the tomb, and air controlling system to solve high humidity condition and dew inside the tomb. For these purposes, detail survery inside and outside the tombs using a electronic distance meter and small airplane, monitoring of temperature and humidity, geophysical exploration including electrical resistivity, geomagnetic, gravity and georadar methods, drilling, measurement of physical and chemical properties of drill core and measurement of groundwater permeability were conducted. We found that the center of the subsurface tomb and the center of soil mound on ground are different 4.5 meter and 5 meter for the 5th tomb and 7th tomb, respectively. The fact has caused unequal stress on the tomb structure. In the 7th tomb (the Muryong royal tomb), 435 bricks were broken out of 6025 bricks in 1972, but 1072 bricks are broken in 1996. The break rate has been increased about 250% for just 24 years. The break rate increased about 290% in the 6th tomb. The situation in 1996 is the result for just 24 years while the situation in 1972 was the result for about 1450 years. Status of breaking of bircks represents that a severe problem is undergoing. The eastern wall of the Muryong royal tomb is moving toward inside the tomb with the rate of 2.95 mm/myr in rainy season and 1.52 mm/myr in dry season. The frontal wall shows biggest movement in the 7th tomb having a rate of 2.05 mm/myr toward the passage way. The 6th tomb shows biggest movement among the three tombs having the rate of 7.44mm/myr and 3.61mm/myr toward east for the high break rate of bricks in the 6th tomb. Georadar section of the shallow soil layer represents several faults in the top soil layer of the 5th tomb and 7th tomb. Raninwater flew through faults tnto the tomb and nearby ground and high water content in nearby ground resulted in low resistance and high humidity inside tombs. High humidity inside tomb made a good condition for algae living with high temperature and moderate light source. The 6th tomb is most severe situation and the 7th tomb is the second in terms of algae living. Artificial change of the tomb environment since the excavation, infiltration of rain water and groundwater into the tombsite and bad drainage system had resulted in dangerous status for the tomb structure. Main cause for many problems including breaking of bricks, movement of tomb walls and algae living is infiltration of rainwater and groundwater into the tomb site. Therefore, protection of the tomb site from high water content should be carried out at first. Waterproofing method includes a cover system over the tomvsith using geotextile, clay layer and geomembrane and a deep trench which is 2 meter down to the base of the 5th tomb at the north of the tomv site. Decrease and balancing of soil weight above the tomb are also needed for the sfety of tomb structures. For the algae living inside tombs, we recommend to spray K101 which developed in this study on the surface of wall and then, exposure to ultraviolet light sources for 24 hours. Air controlling system should be changed to a constant temperature and humidity system for the 6th tomb and the 7th tomb. It seems to much better to place the system at frontal room and to ciculate cold air inside tombs to solve dew problem. Above mentioned preservation methods are suggested to give least changes to tomb site and to solve the most fundmental problems. Repairing should be planned in order and some special cares are needed for the safety of tombs in reparing work. Finally, a monitoring system measuring tilting of tomb walls, water content, groundwater level, temperature and humidity is required to monitor and to evaluate the repairing work.

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