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Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Characterizing Microsatellite Instability in Persian Lynch Syndrome Patients

  • Farahani, Najmeh;Nikpour, Parvaneh;Emami, Mohammad Hassan;Hashemzadeh, Morteza;Zeinalian, Mehrdad;Shariatpanahi, Seyed Shervin;Salehi, Rasoul
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4259-4265
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    • 2016
  • Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20. Materials and Methods: Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data. Results: Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%). Conclusions: Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients.

Retinoid Receptors in Gastric Cancer: Expression and Influence on Prognosis

  • Hu, Kong-Wang;Chen, Fei-Hu;Ge, Jin-Fang;Cao, Li-Yu;Li, Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1809-1817
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    • 2012
  • Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

Experimental Study on GFRP Reinforcing Bars with Hollow Section (중공형 GFRP 보강근의 인장성능 실험연구)

  • You, Young-Jun;Park, Ki-Tae;Seo, Dong-Woo;Hwang, Ji-Hyun
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.19 no.1
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    • pp.45-52
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    • 2015
  • Fiber-reinforced polymer (FRP) has been generally accepted by civil engineers as an alternative for steel reinforcing bars (rebar) due to its advantageous specific tensile strength and non-corrosiveness. Even though some glass fiber reinforced polymer (GFRP) rebars are available on a market, GFRP is still somewhat uncompetitive over steel rebar due to their high cost and relatively low elastic modulus, and brittle failure characteristic. If the price of component materials of GFRP rebar is not reduced, it would be another solution to increase the performance of each material to the highest degree. The tensile strength generally decreases with increasing diameter of FRP rebar. One of the reasons is that only fibers except for fibers in center resist the external force due to the lack of force transfer and the deformation of only outer fibers by gripping system. Eliminating fibers in the center, which do not play an aimed role fully, are helpful to reduce the price and finally FRP rebar would be optimized over the price. In this study, the effect of the hollow section in a cross-section of a GFRP rebar was investigated. A GFRP rebar with 19 mm diameter was selected and an analysis was performed for the tensile test results. Parameter was the ratio of hollow section over solid cross-section. Four kinds of hollow sections were planned. A total of 27 specimens, six specimens for each hollow section and three specimens with a solid cross-section were manufactured and tested. The change by the ratio of hollow section over solid cross-section was analyzed and an optimized cross-section design was proposed.

A Terrain Data Acquisition for Slope Safety Inspection by Using LiDAR (지상 LiDAR에 의한 사면안전진단용 지형정보 취득)

  • Lee, Jong Chool;Kim, Hee Gyoo;Roh, Tae Ho
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.31 no.4
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    • pp.311-319
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    • 2013
  • As heavy rains occur more frequently due to the recent climate change, slope collapses are increasing, and damage to human life and properties is accordingly increasing every year. The most proper method to take preventive measures against slope collapses is to remove the cause after understanding the cause of slope collapse in advance, and for such, slope safety inspection is implemented for preventive purposes, to investigate the cause, and as a measure for restoration. Thus, this Research was able to reach the following conclusion after utilizing LiDAR, which obtains detailed topographic information in a short period of time with point cloud data on slopes subject to safety inspection. First, as a result of analyzing the errors after installing a check point in the subject area, the RMSE of the horizontal location error appeared to be ${\pm}2.2cm$ and the RMSE of the vertical location error appeared to be ${\pm}3.0cm$, which shows a practically satisfactory result. Second, the economic feasibility was outstanding and obtaining accurate topographic information was available. Third, an area once scanned allowed to accurately obtain an unprescribed cross-sectional diagram in a short period of time, thus, appeared to be convenient for experts to detect dangerous sections.

Standardization of Trail Difficulty based on Energy Consumption (에너지 소모량에 기초한 탐방로 난이도 표준화 연구)

  • Hong, Suk-Hwan;Kwon, Tae-Ho;Choi, Song-Hyun;Kim, Kyung-Tae;Kim, Dong-Pil
    • Korean Journal of Environment and Ecology
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    • v.29 no.4
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    • pp.626-635
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    • 2015
  • Recently, the number of trail users in Korea has risen tremendously. Consequently, the cost of safety measures related to hiking is sharply increasing. Despite the safety cost input, the number of heart-related adverse events has been not decreasing. Therefore, this research aims to suggest the use of objective and quantitative trail use information in terms of course difficulty. The study site is Jirisan Dullegil (Jirisan Forest Trail). The currently available trail difficulty information either provides the difficulty rating in terms of 3 to 5 levels according to several empirical difficulty factors reported by staff who maintain the forest or simply states the distance of each trail. Thus, many trail visitors feel a great gap between the given information and actual difficulties they experience. In this study, we tried to assess the degree of difficulty by actual energy consumption. Calculating the volumetric oxygen consumption (VOC) by the distance and gradient not only makes possible an absolute rating but a comparison among the trails as well. Also, it is highly effective to simply describe the exercise intensity of a certain trail. Further, it is easy to check the VOCs' changes by switching the start-end points of the same trail. Providing the trail information of VOCs by sections and directions, we expect to prevent heart-related accidents.

Allowable Compressive Stress of Pre-Tensioned Members with Tee or Inverted Tee Sections at Transfer (T형 및 역T형 단면을 가지는 프리텐션부재의 프리스트레스 도입시 허용 압축응력)

  • Lee, Deuck-Hang;Lee, Jeong-Yeon;Lim, Joo-Hyuk;Kim, Kang-Su
    • Journal of the Korea Concrete Institute
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    • v.23 no.3
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    • pp.353-364
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    • 2011
  • In a previous research performed by the authors, the allowable compressive stress coefficient (K) in pretensioned members with rectangular section at transfer was proposed based on strength design theory. In this study, a subsequent research of an enormous analysis was performed to determine the K factor for Tee and inverted Tee section members, considering the effect of section height (h), section type, amount of tendons ($A_{ps}$), and eccentricity ratio (e/h). Based on the analysis results, the allowable compressive stress coefficients (K) for Tee and inverted Tee section members at transfer were derived, which limit the maximum allowable stresses as 80% and 70% of the compressive strengths at the time of release for Tee section and inverted Tee section, respectively. And these were larger than the allowable stresses specified in domestic and other international codes. In order to verify the proposed equations, they were compared to the test results available in literature and other codes, which showed that the allowable stresses in domestic and international codes are unconservative for the cases with low eccentricity ratios while conservative for those with high eccentricity ratios. The proposed equations, however, estimate the allowable stresses of the Tee and inverted Tee section members reasonably close to test results.

Establishment of Quantitative Method for Generic Drugs in Korea Pharmaceutical Codex Monograph (공정서 수재 의약품의 정량법 개선에 관한 연구)

  • Song, JaeYong;Jang, JinSeob;Jang, SeungEun;Kim, SunHoi;Kim, InKyu;Lee, GilBong;Lee, JeaMan;Kim, YongHee
    • YAKHAK HOEJI
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    • v.56 no.5
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    • pp.288-292
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    • 2012
  • The aim of the paper is to ameliorate old research methods of Korean Pharmaceutical Codex to adjust the newest scientistic level which is necessary to maintain quality of medical supplies effectively. After reviewing result of Establishment of Dissolution Specifications for Generic Drugs in Korea Pharmaceutical Codex Monograph, there are two items chosen for the methods - Establishment of Dissolution Specifications for Generic Drugs in Korea Pharmaceutical Codex Monograph which KFDA researched in 2010, arranged new measuring standard by having an experiment to set measuring method after obtaining each item. According to the result, The experiment includes a measuring method of two items; Nafronyl Oxalate Capsules, and Ticlopidine Hydrochloride Tablets. The research is ameliorated by research methods through several experiments such as High Performance Liquid Chromatography validation, preparing items, implement of trial-experiment and authentic experiment, and experiment on measuring method of regulations of Korea Pharmaceutical Codex. The experiments are taken opinions of experts in KFDA into consideration and wrote out a report of the new measuring method on each last item. The report is combined as each two experiment sections of analyzing method to maintain the quality on the basis of the research in 2010 on setting of dissolution specifications for oral solid dosage forms. The result of measuring method of medical supplies through modernizing trial method of oral solid dosage forms is available to be accurate. In conclusion, this study could contribute to promotion of public health by organizing a basis for safe and high quality of medical supplies in domestic market.

Development of an Imaging Based Gang Protection System

  • Grimm, M.;Pelz, M.
    • International Journal of Railway
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    • v.1 no.4
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    • pp.149-156
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    • 2008
  • During maintenance or construction works in or at the tracks of railways, high risks for passengers and railway staff, especially for the workers on the construction site exist. The high risks result out of the movement of rail vehicles, like trains or construction vehicles, which must be faced by using any available technical and operational technologies for securing them against the environment. Therefore, it is necessary to evaluate the level of protection continuously and to identify new and innovative methods and technologies for the protection of the gang (construction worker, machines and material). Especially on construction sites at line sections with two or more parallel tracks but also with single tracks, there are still a lot of incidents and accidents mostly with seriously injured persons or fatalities. These were mainly gang members that breach the railway-loading gage. By using proper warning or protection systems, the avoidance of such accidents must be achieved. The latest developments. in gang protection systems concern on the one hand fixed barriers in the middle between the construction site and the operated track and on the other hand construction vehicles equipped with automatic warning systems. The disadvantage of such protection methods is that the gang can be warned against an approaching train but a monitoring of the gang members cannot be performed. Only one part of a potential dangerous situation will be detected. If the gang members will overhear the acoustic warning signal of the security staff and the workers will not leave the danger zone in the track, the driver of the approaching train had no chance to react to the dangerous situation. An accident is often inevitable. While the detection of acoustic warning signals by the gang members working on a construction site is very difficult, the acoustical planning of an automatic warning system has to be designed for an acoustic short range level of one meter besides the construction vehicle. The decision about the use of today's technical warning system (fixed systems, automatic warning systems, etc.) must be geared to the technical feasibility and the level of safety which is needed. Criteria for decision guidance to block a track should be developed by danger estimation and economical variables. To realize the actual jurisdiction and to minimize the hazards of railway operations by the use of construction vehicles near the tracks further developments are needed. This means, that the warning systems have to be enhanced to systems for protection, which monitor the realization of the warning signal as a precondition for giving a movement authority to a train. This method can protect against accidents caused by predictable wrongdoing. The actual state of the art technique of using a collective warning combined with additional security staff is no longer acceptable. Therefore, the Institute of Transportation System of the German Aerospace Center in Braunschweig (Germany) will develop a gang warning and protection system based upon imaging methods, with optical sensors such as video in visible and invisible ranges, radar, laser, and other. The advantage of such a system based on the possibility to monitor both the gang itself and the railway-loading gauge either of the parallel track or of the same track still in use. By monitoring both situations, the system will be able to generate a warning message for the approaching train, that there are obstacles in the track, so that the train can be stopped to prevent an accident. And also the gang workers will be warned, while they breach their area.

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Experimental Study for Establishment of Long-term Monitoring System using Fiber Optical Sensor for Pipeline System for Waste Transportation (광섬유센서를 이용한 쓰레기 이송관로의 장기 계측시스템 구축을 위한 실험적 연구)

  • Kim, Haeng-Bae;Song, Jae-Ho
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.20 no.4
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    • pp.35-43
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    • 2016
  • Recently, the pipeline system for waste transportation has been increasingly constructed as new solution for the waste collection and disposal system by constantly increasing domestic waste which issued as social problem. The pipeline system is constructed through long distance, so proper long-term monitoring system is necessary which available to detect the damage location for the effective maintenance. In this paper, the experimental study is carried out to evaluate the applicability of optical strain gauge sensor based on FBG for the long-term monitoring system. Three test parameters such as pressure leaking, blockage and deformation are considered as typical damages for real-scale pipeline test specimen. In order to measure flexural and volumetric strain and temperature, three FBG sensors are installed at each monitoring sections. From the test results, this study suggested effective methods of sensor installation and arrangement. Also the sensor spacing for the design of monitoring system using FBG sensor is derived by the correlation of distances from deformation between sensor responses.

Thyrocyte HLA-DR Expression in Variety of Thyroid Diseases (갑상선 질환들에서 여포세포의 HLA-DR발현)

  • Chang Eun-Sook;Sohn Soo-Sang;Cho Seung-Che;Kim In-Ho;Kim Sang-Pyo;Kang Joong-Shin
    • Korean Journal of Head & Neck Oncology
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    • v.13 no.1
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    • pp.16-23
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    • 1997
  • Although normal thyroid epithelial cells do not constitutively express HLA-DR antigen, their expression in wide spread within thyroid glands obtained from the human with autoimmune thyroid disease and with many neoplastic thyroids. We have, therefore, studied immunohistochemically with regard to the expression of HLA-DR antigen of thyroidectomy specimens from 50 patients of various thyroid diseases with use of paraffin-embedded tissue. One or two sections from each case were stained with commercially available mouse monoclonal antibody for class II HLA-DR antigen(HLA-DR/Alpha, DAKO) and examined by semiquantitative counting system for thyrocytes, neoplastic thyrocytes and other cells expressing HLA-DR antigen. All patients with lymphocytic thyroiditis(2/2) and diffuse hyperplasia(Graves' disease)(5/5), most patients with Hashimoto's disease(9/ll) expressed HLA-DR antigens in thyrocyte with abundant HLA-DR expressing lymphocytic infiltrates with lymph follicle formation in its vicinity or adjacent to the lesion. Most patients with papillary carcinoma(9/1l) had HLA-DR antigen detected in malignant thyrocytes ; while follicular carcinoma(0/3) and follicular adenoma(0/5) did not have detactable HLA-DR immunoreactivity. Adenomatous goiter(3/7) had HLA-DR antigen detected focally in lesser than half cases. Conversely, in four papillary carcinomas and three adenomatous goiters, HLA-DR expression of thyrocytes was found in the absence of HLA-DR expressing lymphoid infiltrates. In such cases therefore other factors more than thyroid autoimmunity must be causative for HLA-DR immunoreactivity. The results of this study indicate as follows. 1) The expression of HLA-DR on thyrocytes involved in autoimmune reactions appeared to be secondary to cytokine release from associated lymphocytic infiltrates. 2) Thyrocytes in thyroid lesions with equal degrees of lymphocytic infiltration without HLA­DR expression exhibited no HLA-DR immunoreactivity. 3) In neoplastic thyrocytes, most papillary carcinoma(9/11) exhibited detactable HLA-DR expression, while follicular carcinoma/adenoma(0/3/0/5) exhibited no detactable HLA-DR immunoreactivity which suggest the existence of divergent mechanisms inducing and modulating HLA-DR expression of different types of neoplastic thyrocytes.

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