(A) TIRAP-derived decoy peptide hinders the TLR4-mediated down-stream signaling

조은영 Ajou University 2019 국내석사

Toll-like Receptor (TLR) signaling cascade proceed with the help of several co-receptors and adaptor proteins resulting in the activation of a protective immune response against the invading pathogens. TLR signaling pathway can be activated through the recruitment of either Myeloid Differentiation factor 88(MyD88) or Toll-Interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF). TLR4, on the other hand, is endowed with the ability of activating both. During the recognition of Lipopolysaccharide (LPS) by TLR4, LPS binding protein (LBP) detaches the monomeric LPS and transfer it to CD14, which in turn exposes the captured LPS to the TLR4/MD2 complex, leading to the subsequent activation of the downstream signaling cascade and the secretion of pro-inflammatory cytokines. However, a dysregulated TLR4 response is often a hallmark of various inflammatory and autoimmune diseases, for this reason, TLRs are being actively pursued as drug targets in the treatment of immune-related disorders. Herein, we report a TIRAP-derived decoy peptide, Ajou5, which displays significant inhibitory effect on TLR4-mediated pathway. In RAW267.4 and THP-1 cells, Ajou5 inhibits the NF-κB activation monitored by SEAP assay, hinders the LPS-induced secretion of inflammatory cytokines such as TNF-α and IL-6, and inhibits the activation of Mitogen-activated protein kinases (MAPKs) and Interferon regulatory factor 3 (IRF3). Ajou5 was unable to inhibit inflammatory cytokines induced by other TLR ligands. In silico data suggested that the interaction of LBP and CD14 is similar to the interaction between Ajou5 and CD14 suggesting that Ajou5 can interrupt ligand transfer to CD14 by delaying the CD14-mediated signaling pathway.

(An) approach to defining the required capability of a weapon system using universal naval task list

원유재 Ajou University 2020 국내박사

The “Needs” function is the first button used to acquire a weapon system in the defense field, this indicate the force required at the mid- and long-term levels in the construction of future military forces. Thus far, Korea has created needs through “Threat-Based Planning,” which plans requirements according to clear threats. From the mid-2000s, the Korean military has focused on strengthening capabilities-based planning by benchmarking the United States Joint Capability Integration and Development System (JCIDS) and re-establishing it as a “Joint Combat Development System.” As the Korean military promoted the establishment of a Joint Combat Development System, each military had to raise a rough capabilities-based requirement. After 2019, each military was required to conduct preconception studies prior to raising the weapons system. The related laws and regulations have been revised so that each military can prepare the operational requirements document (ORD) previously prepared by the Defense Agency Program Administration (DAPA). This requires each military to strengthen its capability of planning requirements, emphasizing the ability of each military to supplement the necessity and characteristics of the weapon system and the completion of the initial requirement at the stage of raising needs. In this manner, while switching to capability-oriented requirements planning and emphasizing the user's initial activities in requirements planning, each military must clearly present the capabilities required for the weapon system to be used during planning. However, each military still raises the need to focus on the performance of a single weapon system through threat-based planning. This is because there is no method for deriving the required capability at each group level, so there is no actual capability demand. Therefore, in this thesis, the method for deriving the requirements of the weapons system centered on the capabilities of each military was studied at the stage of the capability requirement of the joint combat development system. The proposed methodology was defined as a series of processes that leads to concepts, required capabilities, attributes, and metrics, and was established as follows. First, this study focused on 'how to fight' the concept of each military's operation, which should be reflected in the concept of joint action. Upon analyzing the future environment and the mission analysis from the upper level strategic guidelines, the concept of how to perform an operation or function was materialized as a scenario. In addition, the set of activities or functions specified in the operation concept was expressed as the capability the system should have, and the derived capabilities were divided into seven classification systems in the joint capability area of the Korean military. Then, for each capability, the attribute, which is an adjective expression indicating what capability is, was selected, and the measurement criteria were set to quantitatively measure the attribute. To set metrics for each attribute, UNTL (Universal Naval Task List), which is a common task list that presents what needs to be performed by the Navy as an act of conduct during exhibitions and peacetime, was used. The verification of the methodology for defining the required capability proposed in this study was performed considering the requirements derivation, requirements planning, and systems engineering activities. First, based on the operation concept description (OCD) and operation request (ORD), the previous threat-based and capabilities-based planning requirement derivation methods proposed in this study were applied to the coastal combat ship system, respectively. The operating requirements were derived and compared. Next, in terms of planning the requirements, the methods of deriving requirements based on threats and capabilities were evaluated by an accomplished questionnaire using AHP. Third, the previous and the proposed methods were compared and evaluated by applying the Capability Maturity Model Integration (CMMI) considering the organization performing the requirements planning for the weapon system. As a result, the effectiveness of the proposed capabilities-based method for deriving the required capability was confirmed. The significance of this study supports the requirements planning capability of each military by analyzing the method of deriving the capability-centered requirement considering the activities to be performed by the military. Using the results of this study, it is possible to plan requirements focused on the needs of the users. In addition, by using the standardized language from the user's perspective, the capability to be clarified is extended to the system development stage in the future, and is expected to assist the developer in specifying system requirements.

Influence of periodontal infection upon the stage of MRONJ

홍윤표 Ajou University 2017 국내석사

Periodontal diseases and dental diseases are proved as a significant role for Medication related osteonecrosis of the jaw(MRONJ) from many studies. But there has been no study of whether periodontal disease affects not only the onset of MRONJ but also the progression of MRONJ. Thus, The aim of this study is to prove the influence of periodontal infection upon the stage of MRONJ. This study included 86 patients diagnosed with MRONJ, who visited the Department of Dentistry, Oral & Maxillofacial Surgery at Ajou University Hospital from August 2006 to September 2016. Each patient with MRONJ was staged according to the 2014 American Association of Oral and Maxillofacial Surgeons(AAOMS) MRONJ position paper. Each patient’s alveolar bone height was measured by panoramic radiography using Bjorn and Holmberg’s method. There was a significant difference in the alveolar bone height between the MRONJ groups with and without MRONJ infection as seen by the independent t-test (p = 0.004 < 0.05). From this study, Periodontal infection can affect both the risk for developing MRONJ and also the MRONJ stage.

In-bed motion sensor-based wireless network system for improved clinical data analysis

박재연 Ajou University 2020 국내석사

Recently, the advancement in data analytics including various machine learning methods lead to designing effective clinical decision support systems (CDSS) in the clinical sector. However, a CDSS including noisy clinical data can provide unhelpful (if not misleading) decision support to clinical staff as well as clinically dangerous decisions to already suffering patients. Therefore, in order to design a better and effective CDSS, such noisy data caused by patient movements and clinical protocols should be identified and filtered from the inputs in in the training dataset for CDSS development. For this purpose, we propose MediSense a system designed to identify and classify different patient motions on the bed and filter out physiological signal data points collected when patient motion occurs using sensor-based motion classification results. Essentially, MediSense can be considered as ``glasses" for the third eye in accurate-sensitive clinical domain is an intelligent embedded wireless sensing system for supporting a CDSS and consists of a motion classifier, a wireless network and localization techniques. To evaluate our system, we deploy MediSense in intensive care units (ICUs) at the Ajou University Hospital Trauma Center, a major hospital facility located in Suwon, South Korea, and evaluate its each system component's performance from real patient traces collected at these ICUs through a 4-month pilot study. Our results show that MediSense successfully classifies patient motions on the bed with >90% accuracy, shows 100% reliability in determining the locations of beds within the ICU, and each bed-attached sensor achieves a lifetime of more than 33 days, which satisfies the application-level requirements suggested by our clinical partners. Furthermore, a simple case-study with arrhythmia patient data shows that MediSense can help improve the clinical diagnosis accuracy.

Stem cell properties of human fetal cartilage derived progenitor cells as a novel cell source of regenerative medicine

김활란 Ajou University 2018 국내박사

Stem cells research in tissue engineering and regenerative medicine is likely to offer a second generation of therapy for clinical diseases that cannot be treated until now. The stem cells possess two properties, self-renewal and differentiation potential. Differentiation potential of stem cells is the ability to differentiate into specialized cells, in response to appropriate signals. Because of ability to differentiate into different types of functional cells. MSCs are especially the major stem cells for regenerative medicine about approximately 10 years. Because MSCs can be obtained from a variety of tissues.But during long term expansion in vitro, they have disadvantages in terms of decrease differentiation and self-renewal ability as well as characteristic changes of senescence. To application of stem cells in regenerative medicine, in vitro expansion is required to reach the large cell numbers and maintain their character are necessary in order to use the cells. To generate therapeutically safe and usable stem cell-derived products for clinical cell therapies, all animal-derived material must be eliminated from the establishment, culture, and differentiation steps. In the stem cell therapies, the animal-derived reagents was a limitation and risk so in the most researches xeno free conditions is the best choice that do not contain animal components. Elimination of animal components during the in vitro long-term expansion as well as differentiation of stem cells is necessary prior to application in cell therapy. Previously, we demonstrated that characteristics of human fetal cartilage-derived cells (H.FCPCs) as a stem cells in comparison with H.MSCs and young chondrocytes in terms of their proliferation ability and plasticity in vitro and in vivo . And we confirmed that it is a cell source with excellent colony forming ability and no tumorigenicity in vivo.(not published) As well as, H.FCPCs showed low toxicity and immune rejection when injected in a rat model, and the possibility of treatment of synovial arthritis was confirmed.

(A) study on the influence of channel structure on consumer price level

Ofori, Henry Ajou University 2018 국내석사

A channel structure serves as a medium through which economic goods moves from the supplier through the retailer to the final consumer. The retailing section of a channel structure can be described as a common retailing agent or exclusive retailing agent. Where the former sells multi-brand products of numerous manufacturers to consumers while the latter involves selling single brands or products form one manufactures. The products may be acquired from the manufacturers on consignment or straight buying basis. The goal of the study was to identify how these channel forms affect retail prices and consequently consumer welfare. Using the consumer price index of Korea, the analysis of the results revealed that the rates of price increase for consumer products are high for exclusive dealing than common retailing. It was also identified that consignment increases price level more than straight buying but such difference is weakly supported by the data. In terms of the combine distribution structure, exclusive dealing and consignment as one channel form has a higher case of increasing retail prices. The research indicated that one of the factors that can improve consumer welfare is low price. Hence, in a channel structure straight buying and common retailing are the most desirable form of channel structure that can help improve consumer welfare.

(A) study on CTCF recruitment to damaged DNA sites

Ngo, Thanh Hang Ajou University 2018 국내석사

In response to DNA damages, the ATM-Chk2 pathway is rapidly activated following by phosphorylating a number of proteins such γH2AX, Mre11-Rad50-Nbs1 (MRN) complex , p53 and BRCA1, which are involved in cell cycle arrest, apoptosis and DNA repair to maintain genomic integrity. CTCF has been demonstrated to participate in DNA damage repair in addition to various cellular progresses including transcription, insulation, and chromatin architecture but how CTCF is recruited into damaged DNA is still vague. In this study, I showed that recruitment and stable retention of CTCF into DNA lesions are dependent on Chk2 kinase activity but neither ATM kinase nor PARP activity. I also mutated five putative CHK2 phosphorylation serine/threonine to alanine residues in CTCF and evaluated recruitments of these CTCF mutants into damaged DNA sites using micro-irradiation. These putative un-phosphorylatable CTCF mutants are less recruited into the sites of damaged DNA, compared with its wild type In particular, ATM is required for CTCF accumulation at damaged DNA sites, although ATM kinase activity is not necessary. HP1γ and KAP-1 attendance into DNA double-strand break are dependent on CTCF. Finally, both N terminal and zinc finger domains are sufficient to CTCF accumulation on a damaged DNA line of the laser.

Potential neuroprotection against detrimental effects of diabetes and hyperglycemia in ischemic stroke

이성준 Ajou University 2018 국내박사

급성 뇌경색에서 고혈당과 당뇨는 흔한 합병증이며, 조기 신경학적 악화, 뇌경색의 확대, 출혈 변성 및 사망률의 증가와 관련있다. 부분 연구 1 에서 저자들은 당뇨에 병발된 급성 뇌경색에서 혈전 형성 단백인 fibrinogen과 조기 신경학적 악화의 연관성을 분석하였다. 부분연구 2 에서 저자들은 급성 뇌경색에서 혈관내 재개통 시술에 의한 재관류 이후 환자의 예후와 뇌경색의 확대, 출혈 변성과 초기 혈당 수치의 관련성을 분석하였다. 부분 연구 3 에서 저자들은 당뇨 모델 백서에서 DPP-4 억제제인 evogliptin과 metformin 을 독립적으로, 또는 동시에 투여하였을 때 뇌경색의 부피감소에 미치는 영향을 평가하였다. 부분연구 1: 조기 신경학적 악화와 fibrinogen 3814 명의 급성 뇌경색 발생 72시간 이내의 환자를 대상으로 연구를 진행하였다. 조기 신경학적 악화는 입원 7일 이내 National Institutes of Health Stroke Scale (NIHSS) 2점 이상 증가로 정의하였으며, 조기 신경학적 악화의 발생 여부를 propensity score matching을 통하여 당뇨군(조기 신경학적 악화군, n=261; 대조군, n=522) 과 비당뇨군(조기 신경학적 악화군, n=399; 대조군, n=798) 에서 각각 보정하여 분석하였다. Fibrinogen 수치는 전반적으로 조기 신경학적 악화군에서 높았다. 당뇨군에서 fibrinogen 수치는 조기 신경학적 악화의 예측 인자였으나, 비당뇨군에서는 유의한 영향을 보이지 않았다(혈중 fibrinogen 수치 300–599 mg/dL, odds ratio: 1.618 [95% confidence interval: 1.037 – 2.525], p=0.034, 혈중 fibrinogen 수치 ≥600 mg/dL, 2.575 [1.018 – 6.514], p=0.046; 비당뇨군, p=0.393). 본 결과에 따라 당뇨 환자에서 병발한 급성 뇌경색의 경우 혈중 fibrinogen 수치가 조기 신경학적 악화와 연관됨을 보였다. 부분연구 2: 동맥내 재관류 치료 의 예후와 고혈당 다기관 레지스트리를 통해, 2011 년 1월 ~ 2016 년 5월 사이 전순환 대혈관의 급성 폐색으로 동맥내 재관류 치료를 받은 환자들 중 시술 전후 뇌경색 부피를 뇌 자기 공명 확산 가중 영상(diffusion weighted image, DWI)을 통해 평가한 사람을 분석하였다. 내원시 혈당은 정상 혈당(glucose level ≤110 mg/dL), 중도 고혈당(>110 & ≤170 mg/dL), 명백 고혈당(>170 mg/dL)으로 나누어, 열악한 예후(3개월 modified Rankin Scale score 3–6), 뇌경색의 확대, 및 출혈 변성과의 관련성을 분석하였다. 720명의 레지스트리 군 중 341명이 대상이 되었다. 당화 혈색소 수치는 명백 고혈당 군에서 정상 혈당군과 중도 고혈당에 비하여 높았다(p<0.001). 중도 고혈당(2.37 [1.26–4.45], p=0.007)과 명백 고혈당(2.84 [1.19–6.81], p=0.019) 이 열악한 예후와 관련성을 보였다. 시술 후 뇌경색 부피는 전체 고혈당 군에서 유의하게 높았다(padjusted = 0.003). 혈당과 열악한 예후 및 뇌경색 확대는 재관류가 이주어지지 않은 군에서 특히 유의하였다. 명백 고혈당 만이 2 형 실질 혈종와 연관있었으며(9.28 [1.66–51.88], p = 0.011), 재관류 군에서 특히 유의하였다. 부분연구 3: 당뇨 약제의 신경 보호 가능성 6~8주령 백서에서 복강내 streptozotocin 주사로 1형 당뇨를 유발하였다. 백서들에게 30일 동안 대조군, evogliptin, metformin, 또는 evogliptin +metformin 복합요법을 투약하였다. 이후 중뇌동맥 폐색을 일시적으로 유발하여, 발생한 뇌경색의 부피를 T2 뇌 자기공명 영상으로 평가하였다. 그 결과 복합 투여군이 대조군에 비해 유의하게 낮은 뇌경색 부피를 보였다. 혈당 수치는 대조군에 비해 metformin군과 복합 투여군에서 유의하게 낮은 결과를 보인 반면 당화혈색소 수치는 복합 투여군 에서만 대조군에 비해 유의하게 낮았다. 혈장 insulin 수치는 복합 투여군에서 유의하게 높은 결과를 보였다. 본 실험은 1형 당뇨 모델 백서에서 metformin과 insulin 복합 투여가 적절한 혈당 조절 효과와 베타 세포 기능 촉진을 가져올 수 있으며, 이를 통해 허혈 뇌경색의 부피를 감소시킬 수 있음을 보였다. Hyperglycemia and Diabetes mellitus (DM) is a common comorbidity of ischemic stroke, and it is associated with adverse events such as early neurological deterioration (END), infarct growth, hemorrhagic transformation, and increased mortality. In PART I, we evaluated the association between fibrinogen, a prothrombotic protein, and END of diabetic patients with ischemic stroke. In PART II, we evaluated potential effects of admission hyperglycemia on outcomes, infarct growth, and hemorrhagic transformation after endovascular treatment (EVT). In part III, in diabetic rats, we evaluated the ant-ischemic effects of pretreatment with evogliptin, a dipeptidyl peptidase (DPP-4) inhibitor, and metformin, respectively, and combined. PART I: Early Neurological deterioration and fibrinogen We included 3814 ischemic stroke patients within 72 hours of onset. To evaluate the association between fibrinogen and END (National Institutes of Health Stroke Scale [NIHSS] ≥ 2 increase within 1 week of admission), analysis based on propensity score matching between END and non-END population in DM (END, n=261; non-END, n=522) and non-DM populations (END, n=399; non-END, n=798) was performed. Fibrinogen levels were overall higher in the END subgroup compared to non-END subgroup. Only in the DM population were fibrinogen levels an independent predictor for END (fibrinogen levels 300–599 mg/dL, odds ratio: 1.618, 95% confidence interval: 1.037 – 2.525, p=0.034, fibrinogen levels ≥600 mg/dL, 2.575, 1.018 – 6.514, p=0.046; non-DM population, p=0.393). In diabetic patients with acute ischemic stroke, elevated fibrinogen is associated with END dose-dependently. PART II: Adverse effects of hyperglycemia after reperfusion therapy Between January 2011 and May 2016, patients that underwent EVT with pre-procedural and post-procedural diffusion-weighted imaging were identified from a multicenter registry. Normoglycemia was defined as a glucose level ≤110 mg/dL, moderate hyperglycemia as >110 and ≤170 mg/dL, and overt hyperglycemia as >170 mg/dL. Its effects on poor outcomes (3-month modified Rankin Scale score 3–6), infarct growth, and parenchymal hematoma type 2 were analyzed. Of 720 patients encountered, 341 patients were eligible. Glycated hemoglobin levels were higher in overt hyperglycemia group compared to normoglycemia/moderate hyperglycemia group (p<0.001). Moderate hyperglycemia (odds ratio 2.37 [95% confidence interval 1.26–4.45], p=0.007) and overt hyperglycemia (2.84 [1.19–6.81], p=0.019) were associated with poor outcomes. Post-procedural infarct volumes were significantly greater in hyperglycemic patients (padjusted = 0.003). Both findings were confirmed in the total population, and the non-reperfusion subgroup. Only overt hyperglycemia (9.28 [1.66–51.88], p = 0.011) was associated with parenchymal hematoma type 2. This association was confirmed in the total population, and reperfusion subgroup. PART III: Potential neuroprotection of antidiabetic drugs Type 1 diabetes was induced by intraperitoneal injection of streptozotocin in rats aged 6~8 weeks. The rats were treated with vehicle, evogliptin, metformin, or evogliptin/metformin co-administration for 30 days. Stroke was induced by transient middle cerebral artery occlusion afterwards. Ischemic damage was measured by determining infarct volume through T2 weighted magnetic resonance imaging. The results showed pronounced reduction of infarct volume in the co-administration group. Blood glucose lowering effects were significant in the metformin group and co-administration group, while glycated hemoglobin levels were significantly lower in the co-administration group. Plasma insulin levels were significantly higher in the co-administration group. These results show that combined treatment of metformin and evogliptin provide further glycemic control, improve beta cell function and offer neuroprotective effects against ischemic stroke.

Validation study of the Korean version of the Reward Probability Index (RPI)

안보미 Ajou University 2018 국내석사

The purpose of the current study was to translate and validate the Reward Probability Index(RPI) developed by Carvalho and colleges(2011) with Korean adults. Exploratory Factor Analysis conducted with non-clinical 300 adults reported a two factor structure with 15 items. Confirmatory Factor Analysis with 400 non-clinical adults supported the two factor model. Results indicate a strong factor structure, internal consistency and test-retest reliability. Convergent and divergent validity were also supported. Study 2 applied the Korean RPI to examine the relationship between negative affectivity and depression. As a result, Experiential Avoidance and Reward Probability partially mediated the relationship between Negative Affectivity and Depression. These findings suggest that negative affectivity indirectly had an impact on depressive symptoms through the signifiant mediating effects of experiential avoidance and reward probability. Based on these results, implications, limitations, and suggestions for future research were discussed.

Small file indexing scheme for HDFS with erasure coding

Terefe, Anene Bekuma Ajou University 2018 국내석사

Hadoop Distributed File System (HDFS) is designed to store and manage large files. It stores the file system metadata in the NameNode’s memory for high performance. Since there is a single NameNode in HDFS cluster, it suffers from high memory usage of the NameNode when processing a massive number of small files. This problem is referred as ‘the small file problem’. The small file problem occurs because HDFS stores each small file on a separate storage block in the DataNode and maintains an individual metadata on the NameNode. Researchers suggested merging small files to large file with a size of one HDFS block to reduces the memory usage of the NameNode. They considered HDFS with contiguous block layout to solve the small file problem. However, a striped block layout has been adopted by Hadoop when Erasure Coding is enabled. In this block layout, a file is divided into smaller parts of 1MB size and distributed across multiple storage blocks of a DataNode. As a result, it creates a possibility to further reduce the memory usage of the small files by increasing the merged file size to fully fill the multiple storage blocks while maintaining the same size of metadata. Therefore, we propose a new scheme for solving the small file problem that further reduces the memory usage of the NameNode by considering a striped block layout. However, it brings a new challenge as it needs a novel file indexing and file extracting methods to access the small files. We introduced a program named Small File Processor (SFP) which performs file merging and indexing on small files. A file extracting algorithm has been implemented to read the small files from their corresponding merged file. The experiment result shows that the proposed scheme reduces the memory usage of NameNode and improves the write access speed of the small files compared to the default HDFS with Erasure Coding.