c-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression

Receptor tyrosine kinases (RTKs) are important targets for clear cell renal cell carcinoma (ccRCC) treatment. Myoferlin is a strong regulator of RTKs. To identify myoferlin-associated RTKs and their prognostic implications in ccRCC, we investigated the expression of RTKs and myoferlin using proteome-based evaluation and immunohistochemical staining in tissue microarray. Multivariate Cox analysis adjusted for TNM stage and WHO grade was performed (n = 410 and 506). Proteomic analysis suggested c-Met and EPHA7 as novel candidates for myoferlin-associated RTKs. We immunohistochemically validated the positive association between c-Met and myoferlin expression. High c-Met expression was independently associated with overall (hazard ratio (HR) = 1.153-2.919) and cancer-specific survival (HR = 1.150-3.389). The prognostic effect of high c-Met expression was also determined in an independent cohort (overall survival, HR = 1.503-3.771). Although expression of EPHA7 and myoferlin was not correlated, EPHA7 expression was independently associated with progression-free (HR = 1.237-4.319) and cancer-specific survival (HR = 1.214-4.558). In addition, network-based prioritization showed co-functional enrichment of c-Met and myoferlin, suggesting a novel regulatory function of myoferlin in c-Met signaling. This study indicates that c-Met and EPHA7 might be useful prognostic biomarkers, and the presumed myoferlin/c-Met pathway could be a novel therapeutic target in ccRCC.ope

Prognosis in primary mucinous ovarian carcinoma: focusing on the five pathological findings indicating metastatic mucinous carcinoma to the ovary

Objective: Pathological features indicating metastatic mucinous carcinoma to the ovary (MMCO) have been rarely reported in primary mucinous ovarian carcinoma (PMOC). However, little is known about how often they are observed in PMOC and how they relate to patient prognosis. In this study, we investigated the pathological features indicating MMCO in a large cohort of PMOCs and analyzed their association with patient prognosis. Methods: We reviewed surgically treated PMOC patients diagnosed at the Seoul National University Hospital from 1995 to 2019, according to the updated WHO classification, and investigated the presence of pathological features indicating MMCO. Results: A total of 144 patients with PMOCs were included. The 5 pathological findings indicating MMCO, including an infiltrative invasive pattern, the absence of benign or borderline components, a smaller tumor size, the presence of signet ring cells and the presence of extracellular mucin were observed in PMOC (21.6%, 43.1%, 20.8%, 4.3% and 12.9%, respectively), and were significantly correlated with poor overall and progression-free survival rates in PMOC. The patient's prognosis worsened as the extent of the infiltrative invasive pattern increased (p<0.001). In addition, the prognostic power was stronger when the 5 pathological factors were analyzed together (new grouping system) than when analyzed individually (p<0.001) and the new grouping system was identified as an independent prognostic factor regardless of FIGO stage. Conclusion: Five pathological findings indicating MMCO in PMOC were significantly associated with poor prognosis in PMOC patients. Also, the new grouping system combining these findings was identified as an independent prognostic factor.ope

Proteomic-Based Machine Learning Analysis Reveals PYGB as a Novel Immunohistochemical Biomarker to Distinguish Inverted Urothelial Papilloma From Low-Grade Papillary Urothelial Carcinoma With Inverted Growth

Background: The molecular biology of inverted urothelial papilloma (IUP) as a precursor disease of urothelial carcinoma is poorly understood. Furthermore, the overlapping histology between IUP and papillary urothelial carcinoma (PUC) with inverted growth is a diagnostic pitfall leading to frequent misdiagnoses. Methods: To identify the oncologic significance of IUP and discover a novel biomarker for its diagnosis, we employed mass spectrometry-based proteomic analysis of IUP, PUC, and normal urothelium (NU). Machine learning analysis shortlisted candidate proteins, while subsequent immunohistochemical validation was performed in an independent sample cohort. Results: From the overall proteomic landscape, we found divergent 'NU-like' (low-risk) and 'PUC-like' (high-risk) signatures in IUP. The latter were characterized by altered metabolism, biosynthesis, and cell-cell interaction functions, indicating oncologic significance. Further machine learning-based analysis revealed SERPINH1, PKP2, and PYGB as potential diagnostic biomarkers discriminating IUP from PUC. The immunohistochemical validation confirmed PYGB as a specific biomarker to distinguish between IUP and PUC with inverted growth. Conclusion: In conclusion, we suggest PYGB as a promising immunohistochemical marker for IUP diagnosis in routine practice.ope

ALK Translocation in ALK-Positive Mesenchymal Tumors: Diagnostic and Therapeutic Insights

Context.—: A wide spectrum of mesenchymal tumors harboring ALK gene rearrangements has been identified outside the archetypal example of ALK-positive inflammatory myofibroblastic tumors. Objective.—: To evaluate the molecular pathology of unusual ALK-positive mesenchymal tumors and their response to ALK-targeted treatments. Design.—: Seven patients with ALK-positive mesenchymal tumors, including inflammatory epithelioid cell sarcoma, undifferentiated sarcoma, histiocytic neoplasm, smooth muscle tumor of uncertain malignant potential (STUMP), and atypical fibrohistiocytic tumor, were included on the basis of aberrant ALK immunoexpression. Patients with inflammatory myofibroblastic tumors were excluded from the study. ALK gene rearrangement was investigated either by fluorescence in situ hybridization or next-generation sequencing. Results.—: ALK was immunolabeled in all patients, diffusely (≥50%) in 6 patients and partially (10%-50%) in 1 patient. ALK gene rearrangement was discovered in 5 of the 6 available patients. The 3'-partners of ALK fusion were identified in 3 of 4 investigated patients as follows: PRKAR1A-ALK (ALK-positive histiocytic neoplasm), TNS1-ALK (STUMP), and KIF5B-ALK (ALK-positive atypical fibrohistiocytic tumor). We failed to discover ALK translocation in 1 patient with ALK-positive inflammatory epithelioid cell sarcoma. However, transcriptomic investigation showed that this tumor was significantly enriched with ALK-related pathways, which suggested activation of ALK through a nontranslocation pathway, as a constitutive oncogenic mark in this tumor. ALK-targeted inhibitors, which were administered to 3 patients with metastatic diseases, achieved partial remission in 1 patient with ALK-positive inflammatory epithelioid cell sarcoma and stable disease in patients with ALK-positive undifferentiated sarcoma and STUMP. Conclusions.—: Molecular investigation of ALK-positive mesenchymal neoplasms could allow for an accurate diagnosis and personalized treatment.ope

Nicotinamide (niacin) supplement increases lipid metabolism and ROS-induced energy disruption in triple-negative breast cancer: potential for drug repositioning as an anti-tumor agent

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water-soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM-induced metabolic regulation and the therapeutic efficacy of NAM in triple-negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β-oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next-generation anti-metabolic agent for TNBC treatment.ope

Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas

Although the density of tumor-infiltrating lymphocytes (TILs) is known to be linked to prognosis in various cancers, the prognostic impact and immunologic significance of the spatial heterogeneity of TILs have been rarely investigated. In this study, CD3+ and CD8+ TILs were quantified in independent cohorts (discovery, n = 73; and external validation, n = 93) of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) utilizing whole-slide image analysis of CD3/CD8 immunohistochemistry. The Shannon and Simpson indices, which measure intratumoral patch-to-patch evenness of TIL densities, were used to quantitatively assess the spatial heterogeneity of TILs in each case. To uncover immune-related gene expression signatures of spatial heterogeneity-based TIL subgroups of MSI-H CRCs, representative cases were subjected to GeoMx digital spatial profiler (DSP) analysis. As expected, a low density of TILs was significantly associated with poor disease-free survival (DFS) in MSI-H CRCs. The TIL-low tumors were further classified into two subgroups based on the spatial heterogeneity of TILs: TIL-low/heterogeneity-high and TIL-low/heterogeneity-low subgroups. In both discovery and validation cohorts, the TIL-low/heterogeneity-high, TIL-low/heterogeneity-low, and TIL-high subgroups were significantly associated with poor, intermediate, and good DFS, respectively. In the DSP analysis, the TIL-low/heterogeneity-high subgroup showed higher spatial diversity in the expression of immune-related genes than that of the TIL-low/heterogeneity-low subgroup and exhibited upregulation of genes related to immune checkpoints, chemokine/cytokine receptors, and myeloid cells. TIL-low/heterogeneity-high tumors were also enriched with gene sets related to good response to immune checkpoint inhibitor therapy. In conclusion, TIL-low MSI-H CRCs are prognostically heterogeneous and can be divided into prognostically and immunologically distinct subgroups by considering the spatial heterogeneity of TILs. Our data suggest that intratumoral spatial heterogeneity of TILs can be used as a key element for clinically relevant immunologic subtyping of tumors.restrictio

다양한 calcium silicate cement가 적용된 염증 치수의 염증 반응 및 odontogenic 분화

치수 노출은 치아우식증, 외상 또는 의원성 원인에 의해 임상에서 흔히 나타난다. 생활 치수 치료는 치수 노출이 발생한 경우 치아 생활력을 유지할 수 있는 치료 방법이다. 이때 치수 복조에 사용하는 재료는 이러한 보존적인 치료의 결과에 영향을 미치는 중요한 요인으로 알려져 있으며, calcium silicate cements (CSCs)는 우수한 생체적합성 및 경조직 유도능을 보이기 때문에 가장 이상적인 치수 복조 재료로 평가되고 있다. 현재까지 많은 연구들이 CSC 의 세포 및 조직 반응을 연구하였으나,대부분의 과거 연구들은 CSC 가 정상 치수에 미치는 영향을 평가하였다. 이와 다르게 본 연구는 염증 치수에 다양한 CSC 를 적용하였을 때 나타나는 치수 반응을 in vitro 및 in vivo 로 분석하였다. 본 연구의 목적은 (1) 리포폴리사카라이드 (LPS) 처리한 치수줄기세포의 다양한 CSC 에 대한 염증 반응 및 odontogenic 분화를 연구하는 것과 (2) 다양한 CSC 로 쥐의 염증 치수 모델에 직접 치수 복조를 시행하였을 때 나타나는 염증 반응 및 경조직 형성을 평가하는 것이었다. In vitro 실험의 경우, 인간 치수줄기세포를 p.gingivalis LPS 로 염증을 유도하고 ProRoot MTA (Dentsply, Tulsa, OK, USA), Biodentine (Septodont,Saint-Maur-des-Fossés, France), RetroMTA (Bio MTA, Seoul, Korea) 및 Dycal (Dentsply Caulk, Milford, DE, USA)와 같이 배양하였다. 재료 처리 12, 24, 48 시간 후, interleukin (IL)-6, IL-8, 및 transforming growth factor (TGF)-β1 의 발현을 효소결합면역흡착검사 (ELISA)를 이용하여 측정하였고, alkaline phosphatase (ALP), osteocalcin (OCN), 및 runt-related transcription factor 2 (RUNX2)를 실시간 중합효소 연쇄반응 (qPCR)로 평가하였다. 염증 사이토카인 및 odontogenic marker 의 발현을 일원배치 분산분석을 이용하여 평가하였다 (p < 0.05). In vivo 로 치수 반응을 관찰하기 위하여 Wistar rat 의 대구치에 미세한 치수 노출을 동반하는 와동을 형성하고 48 시간 동안 개방하여 치수 염증을 유도하였다. 그 후, 노출된 치수에 ProRoot MTA, Biodentine, RetroMTA 또는 Dycal 로 복조를 시행하였다. 1, 2, 4 주 후 동물을 조직학 시편 형성을 위하여 희생한 후, hematoxylin-eosin 염색을 시행하여 치수 염증 및 경조직 형성 정도를 평가하고 점수를 부여하였으며, IL-6, OCN and RUNX2 면역형광염색도 진행하였다. Pearson 의 카이 제곱 검정을 이용하여 재료 군간 염증 및 경조직 형성 점수를 비교하였다 (p < 0.05). LPS 가 처리된 인간치수줄기세포 (LDPSCs)에서, RetroMTA 가 48 시간에서 유의하게 IL-6 및 IL-8의 발현을 감소시켰으며, ProRoot MTA 및 Biodentine이 12 시간 및 48 시간에서 TGF-β1 의 발현을 유의하게 감소시켰다. LDPSCs 의 ALP 발현은 CSCs 에 의해 유의한 영향이 없었으나, Dycal 군의 경우 유의하게 증가한 ALP 발현이 관찰되었다. Biodentine, Retro MTA 및 Dycal 은 OCN 의 발현을 증가시켰으며, 모든 재료가 12 시간에서 LDPSCs 의 RUNX2 의 발현을 증가시켰다. 쥐의 염증 치수 복조 실험에서, 치수 복조 1 주일 후 경미한 염증과 경조직 형성의 개시가 확인되었으며 IL-6, OCN 및 RUNX2 의 미약하거나 불명확한 발현만이 관찰되었다. 치수 복주 2 주 뒤, 더 많은 비율의 조직 샘플들이 중등도 염증을 나타내었고, 중등도 또는 다량의(heavy) 경조직 형성이 나타났다. 면역형광염색의 경우, 모든 재료군에서 IL-6 가 관찰되었지만, RUNX2 와 OCN 은 Biodentine 군에서만 확인되었다. 치수 복조 4 주 후, ProRoot MTA 군의 22%, Biodentine 군의 37.5%, RetroMTA 군의 10%에서 염증 상태로부터 완전한 회복이 관찰되었다. Dycal 군의 경우 염증이 없는 시편은 존재하지 않았다. 완전하고 연속적인 경조직 브릿지는 ProRoot MTA 군의 77.8%, Biodentine 군의 75%, Retro MTA 군의 70%, Dycal 군의 60%에서 발견되었다. IL-6, OCN 및 RUNX2 의 발현이 모든 재료군에서 염증 및 삼차상아질 형성 부위 근처에서 확인되었다. 치수 복조 1, 2, 4 주 뒤 결과 모두에서 재료군 간 염증 및 경조직 형성 점수의 통계학적 유의차는 없었다. 본 연구에서, 염증 치수를 CSC 로 복조하였을 때, 술식 4 주 뒤에도 대부분의 시편에서 치수 내 염증이 관찰되었으며, 일부 샘플에서 불완전하고 불연속적인 상아질 브릿지 형성이 관찰되었다. 이러한 결과는 치수의 술전 염증의 존재가 CSC 로 치료된 치아들의 예후를 불량하게 할 수 있는 요인이 될 수 있을 가능성을 제시한다. Pulp exposure is a relatively common clinical occurrence due to dental caries, trauma or iatrogenic causes. Vital pulp therapy is an approach that can be considered for treating pulp exposure to preserve pulp vitality. The type of pulp capping material is a crucial factor that affects the outcome of these conservative treatment procedures, and calcium silicate cements (CSCs) are regarded as the ‘gold-standard’ of pulp capping materials due to its superior biocompatibility and hard tissue induction potentials. Various studies have evaluated the cell and tissue responses of CSCs, however, most papers have studied their effects on normal dental pulp, and studies on the effect of CSCs on inflamed pulp are yet limited. This study investigated the pulpal responses of inflamed dental pulp to different CSCs in vitro and in vivo. The purposes of this study were (1) to investigate the inflammatory response and odontogenic differentiation of lipopolysaccharide (LPS)-induced dental pulp stem cells (LDPSCs) using different CSCs and (2) to test the inflammation and hard tissue formation of inflamed rat dental pulp after direct pulp capping with CSCs. For the in vitro assessment, human dental pulp stem cells were stimulated with p.gingivalis LPS, and these LDPSCs were cultured with ProRoot MTA (Dentsply, Tulsa, OK, USA), Biodentine (Septodont, Saint-Maur-des-Fossés, France), RetroMTA (Bio MTA, Seoul, Korea) and Dycal (Dentsply Caulk, Milford, DE, USA). Interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-β1 expressions were assessed by enzyme-linked immunosorbent assay, and the mRNA expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) were analyzed by quantitative real-time polymerase chain reaction for 12, 24 and 48 hours (h). The levels of inflammatory cytokines and expressions of odontogenic markers were evaluated using one-way analysis of variance followed by the Tukey’s test (p < 0.05). In order to test the in vivo pulpal responses, cavities with pin point pulp exposure were prepared on molars of Wistar rats. The cavities were left open for induction of inflammation. After 48 h, the exposed pulp was capped with ProRoot MTA, Biodentine, RetroMTA or Dycal. After one, two, or four weeks, animals were sacrificed for histologic specimens. Samples were stained with hematoxylin-eosin, and pulpal inflammation and hard tissue formation were evaluated based on a scoring criteria. Immunofluorescence staining of IL-6, OCN and RUNX2 were also performed. Pearson’s chi-square test was used to analyze the inflammation and hard tissue formation scores of different material groups (p < 0.05). Regarding LDPSCs, RetroMTA significantly decreased levels of IL-6 and IL-8 of at 48 h, and ProRoot MTA and Biodentine significantly reduced TGF-β1 expression at 12 and 48 h. ALP expression of LDPSCs was not effected by CSCs, but was increased by Dycal. OCN expression was significantly increased by Biodentine, RetroMTA and Dycal. All pulp capping materials significantly increased RUNX2 expression of LDPSCs at 12 h. In the rat inflamed pulp capping model, mild inflammation and initiation of hard tissue formation was observed at one week, with weak or unapparent IL-6, OCN and RUNX expressions. Two weeks postoperatively, an increased percentage of samples showed moderate inflammation, and moderate or heavy hard tissue formation was observed. IL-6 positive signals were found in all material groups, but expressions of RUNX2 and OCN were only apparent in Biodentine. After four weeks, complete recovery from inflammation was evident in 22% of ProRoot MTA, 37.5% of Biodentine, 10% of RetroMTA samples. Specimens without inflammation were not observed in the Dycal group. Heavy hard tissue deposition as a continuous dentin bridge was observed in 77.8% of ProRoot MTA, 75% of Biodentine, 70% of RetroMTA and 60% of Dycal samples. IL-6 was detected in all material groups. Positive traces of OCN and RUNX2 were visible in all materials. IL-6, OCN and RUNX2 were mainly detected adjacent to areas of inflammation and reparative dentin formation. Pulpal responses for the four materials groups were not statistically significant at one, two and four weeks. In this study, at four weeks after pulp capping, pulpal inflammation was still present in most specimens, and a significant number of samples showed incomplete and discontinuous dentin bridge formations. The results of this study suggest that initial inflammatory conditions of the pulp may jeopardize the prognosis of teeth treated with CSCs.open박

The proteomic landscape shows oncologic relevance in cystitis glandularis

Background: The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. Methods: We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. Results: We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. Conclusions: Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.ope

A Study on the Utilization of BWIM Using Theoretical Response of Bridge

교량에서 교통량증가 및 차량의 적재율의 증가로 인하여 활하중 및 피로하중의 증대는 교량 안전성 및 유지관리에서 중요한 영향을 미칠 수 있다. 이러한 하중을 정확히 파악하기 위해서는 통과차량의 하중평가 및 통행특성을 파악하는 것이 필요하다. 이 연구에서는 플레이트 거더교의 주거더 하부플랜지 및 수직보강재에서 발생하는 변형의 응답을 해석적으로 도출하여 임의 통과차량의 특성 및 중량을 산정하는 BWIM(Bridge Weight-In-Motion)활용방안에 대해 분석하고자 한다. 동적프로그램인 DAP-1을 사용하여 다양한 실제 차량을 모델링 하여 시간이력해석을 수행하였다. 이로부터 차량특성에 따른 시간이력해석을 주거더 및 수직보강재를 대상으로 산출하여 주행차량의 위치, 속도, 축간거리를 분석하였다. 또한 교량의 동적거동을 반영한 영향선을 도출하였고 이를 기초로 역계산을 통하여 차량중량을 분석하였다. 연구결과, 짧은 부재의 시간이력응답을 1계 미분하여 차량의 위치 및 속도를 검출 하는 것이 실시간 계측에 가장 적합한 것으로 나타났다. 또한 비교적 긴 부재의 응답으로 영향선을 구하여 중량을 산출하는 것이 실시간계측에 적합한 것으로 나타났다.Due to increase of traffic and vehicle loading, increase in live load and fatigue load has a major impact on safety and maintenance in bridge. In order to determine the exact load, it is necessary to clearly understand of the load evaluation and traffic characteristics. In this study, response of strain data theoretically acquired from bottom flange and longitudinal stiffener of plate girder bridge, utilization of Bridge Weigh-In-Motion(BWIM), which calculate the characteristic and weight of pass vehicle, are analysed. Various real vehicle modeling was performed by using the DAP-1 that is a dynamical program to analysis the time history. From this performing, vehicle location, speed, wheelbase were analyzed by the time history analysis based on vehicle characteristics of main girders and vertical reinforcement. Also the influence line that reflects the dynamic behavior was drawn. As a result of the influence line, the weight of the vehicle was analyzed by reversely calculating. As a result of this study, it is the most suitable that the response time history of the short members differentiate to detect position and velocity of the vehicle. In addition, to calculate the weight as a result of Influence line based on the response of the relatively long material is the most suitable.목 차 ABSTRACT=ⅰ 요약=ⅲ 목차=ⅳ 표목차=ⅵ 그림목차=ⅷ 1장. 서론=1 1.1 연구의 배경과 목적=1 1.2 BWIM 개요=3 1.2.1 영향선이 긴 교량부재의 응답을 이용하는 방법=4 1.2.2 영향선이 짧은 교량부재의 응답을 이용하는 방법=6 1.3 국내외 연구동향=7 1.3.1 국내 연구동향=7 1.3.2 국외 연구동향=8 1.4 연구의 범위 및 구성=10 2장. Bridge Weigh-In-Motion(BWIM) System=12 2.1 BWIM System 산정=12 2.1.1 기본구성=12 2.1.2 산정흐름=14 2.1.3 차량 위치산정 방법=15 2.1.4 차량 속도산정 방법=17 2.1.5 영향선산정 방법=20 2.1.6 차량 중량산정 방법=22 3장. 수치해석에 따른 차량중량추정방법=24 3.1 대상교량의 제원 및 특성=24 3.2 이동하중에 따른 시간이력해석=25 3.2.1 시간이력 해석개요=25 3.2.2 해석변수 및 조건=27 3.2.3 시간이력해석에 따른 교량응답 결과=30 3.3 시험차량에 따른 BWIM 분석=32 3.3.1 차량의 위치분석=32 3.3.2 차량의 속도분석=35 3.4 시험차량 주행시의 중량분석=40 3.4.1 영향선 산출=40 3.4.2 중량 산출=42 4장. BWIM System의한 중량산출=50 4.1 BWIM System을 활용한 중량산출=50 4.1.1 영향선함수를 이용한 중량산출=50 4.1.2 영향면적을 이용한 중량산출=54 4.2 차량의 주행조건에 따른 중량산정=56 4.2.1 속도에 따른 중량정밀도=56 4.2.2 축간거리에 따른 중량정밀도=60 4.2.3 횡방향 이동에 따른 중량정밀도=63 5장. 결론=75 5.1 결론=75 5.2 향후 과제=77 참고문헌=78 부록=8