CCR3 를 통한 염증 신호를 일으키는 NRS N 말단 부위에 대한 구조생물학적 연구

학위논문 (박사)-- 서울대학교 대학원 : 약학대학 약학과, 2019. 2. 한병우.Antisynthetase syndrome 은 autoimmune disease 의 하나로, aminoacyl-tRNA synthetase 에 대한 antibody 가 만들어진다. 그 중에서 asparaginyl-tRNA synthetase 에 대한 autoantibody 인 anti-KS 의 발생은 interstitial lung disease 와 밀접한 관련이 있는 것으로 보이는데 아직 생성 기전이 명확하게 밝혀지지 않았다. 본 연구에서는 human asparaginyl-tRNA synthetase 의 N 말단 부위의 결정구조를 규명하였고 그 구조가 Brugia malayi asparaginyl-tRNA synthetase 의 N 말단 부위와 유사하다는 것을 밝혔다. 또한 human asparaginyl-tRNA synthetase 의 N 말단 부위가 CC chemokine receptor 3 와 직접 결합하여 독립적으로 chemokine 활성을 가진다는 것을 보였고, 그 결합 방식을 NMR spectroscopy 기법을 이용하여 설명하였다. 나아가, interstitial lung disease 의 발달과 autoantibody 의 생성에 있어 human asparaginyl-tRNA synthetase 의 증가된 분비에 따른 비정상적인 N 말단 부위의 chemokine 활성이 잠재적 역할을 할 것이라 제시하였다.Asparaginyl-tRNA synthetase (NRS) is not only essential in protein translation but also associated with autoimmune diseases. Particularly, patients with antibodies that recognize NRS often develop interstitial lung disease (ILD). However, the underlying mechanism of how NRS is recognized by immune cells and provokes inflammatory responses is not well-understood. Here, I found that the crystal structure of the unique N-terminal extension domain of human NRS (named as UNE-N, where -N denotes NRS) resembles that of the chemotactic N-terminal domain of NRS from a filarial nematode, Brugia malayi, which recruits and activates specific immune cells by interacting with CXC chemokine receptor 1 and 2. UNE-N induced migration of C-C chemokine receptor 3 (CCR3)-expressing cells. The chemokine activity of UNE-N was significantly reduced by suppressing CCR3 expression with CCR3-targeting siRNA, and the loop3 region of UNE-N was shown to interact mainly with the extracellular domains of CCR3 in nuclear magnetic resonance perturbation experiments. Based on these results, evolutionarily acquired UNE-N elicits chemokine activities that would promote NRS-CCR3-mediated proinflammatory signaling in ILD.1. Introduction 1 1.1. Aminoacyl-tRNA synthetase . 1 1.2. Class 2b ARS . 10 1.3. Chemokine activities of NRS . 12 1.4. Antisynthetase syndrome . 14 1.5. Chemokine 16 1.6. Summary 18 2. Materials and Methods . 19 2.1. Cloning, protein expression, and purification . 19 2.2. Selenomethionine incorporation 28 2.3. Crystallography 28 2.4. NMR analysis . 35 2.5. Cell culture . 36 2.6. Cell migration assay 37 2.7. Secretion assay 38 2.8. Immunoblotting 39 2.9. Pull-down assay 39 2.10. Statistical analysis . 40 2.11. Data deposition 40 3. Results 41 3.1. UNE-N shares a structural scaffold with the chemotactic N-terminal domain of BmNRS but exhibits unique features 41 3.2. Th1 and Th2 cytokines induce NRS secretion from macrophages 56 3.3. UNE-N exclusively elicits chemotactic activities of NRS on Daudi and Jurkat cells 60 3.4. UNE-N directly interacts with CCR3 extracellular domains 64 3.5. Loop3 of UNE-N is an effector motif for CCR 3interactions 68 3.6. Loop3 region of UNE-N is structurally distinct from UNE-N of BmNRS targeting different receptors . 75 4. Discussion . 79 5. References 88 6. Abstract in Korean (국문 초록) 96Docto

Frey's procedure for chronic pancreatitis: a 10-year single-center experience in Korea

Purpose: Chronic pancreatitis (CP) is progressive inflammatory disease that leads to irreversible destruction of the pancreatic parenchyma. The main indications for surgical intervention in cases involving CP are intractable pain, suspicion of malignancy, and failure of other methods. However, there is no report related to Frey's procedure in Korea; hence, we aimed to investigate and analyze our institution's experience and determine the benefits of surgical treatment for CP. Methods: This was a retrospective study of 24 patients with CP who underwent Frey's procedure at Gangnam Severance Yonsei University between January 2007 and December 2017. Preoperative exocrine and endocrine pancreatic function, perioperative finding (blood loss, operation time), postoperative complications were evaluated. Statistical analytics were chi-square test, Fisher exact tests, and Wilcoxon signed-rank test and Mann-Whitney U-test. Results: Surgery was performed due to alcohol-derived CP in 12 of 24 patients (50%) and due to pancreatic stones in 15 of 24 patients (62.5%). Two patients had postoperative complications which were managed conservatively. After surgery, 7 of 24 patients were prescribed with exocrine medication. Comparison of the preoperative and postoperative conditions showed that glycated hemoglobin had no significant differences. After surgery, only 5 patients (21%) complained of intermittent abdominal pain. Conclusion: In conclusion, Frey's procedure appears to be a less burdensome surgical procedure. Thus, it could be the first option for management of patients with large pancreatic stone.ope

Clinical application of invalid foods using mealworms and evaluation of nutrition status and immune function: a study protocol for a randomized, double blind, placebo-controlled trial

Background Protein intake is important for the recovery of the immune system, physical strength, and wound healing after surgery. Sarcopenia is associated with a poor prognosis when compared to patients without sarcopenia in cancer patients. Recently, edible insects, such as mealworms, have been recognized as having a high protein content. In this study, we will evaluate the effect of nutritional status and immune function change based on a patient’s ingestion of mealworms after hepatobiliary pancreatic surgery. Methods/design This is a prospective, two-armed, phase III study investigating the effect of mealworm improving nutrition and immune status in patients after hepatobiliary pancreatic surgery. In the trial group, the patients will be provided with mealworms for 2 months after surgery. In the control group, patients will be provided with grain powder for 2 months after surgery. The target for accrual is 168 patients. We divided in to three groups according to the type of surgery. Discussion The primary endpoint is to evaluate body cell mass index 2 months postoperatively. Secondary endpoints include other body composition changes as well as nutrition index and immune function change. We expect that ingestion of mealworms can effectively improve the nutritional status and enhance the immune function. Mealworm can be used effectively for nutritional management of patients after surgery. Trial registration Clinicaltrials.gov NCT03201926 Registered June 28, 2017, retrospectively registered.ope

P16 and MGMT hypermethylation predicts surgical outcomes in curative resected mid/distal bile duct cancer

Dept. of Medicine/박사Extrahepatic bile duct cancer is a primary malignancy arising from epithelium of extrahepatic biliary tract. In patients with extrahepatic bile duct carcinoma, the 5-year survival rate was 38.3%; a very poor prognosis has been reported. In these patients, the important prognostic factors include the TNM stage, cell differentiation and histologic type. Nevertheless, we often encounter a substantial number of patients whose prognosis is not consistent with the TNM stage. Therefore, other prognostic criteria are mandatory than the TNM staging system which has been widely used at present. We aimed to evaluate the potential role of DNA promoter methylation of gene involved in a variety of celluar function including adhesion (CDH1), cell division (p16) and survival (DAPK), to predict disease free survival (DFS) and overall survival (OS) in curative resected mid/distal bile duct cancer. Sixty-five mid/distal bile duct carcinoma specimens obtained at Severance Hospital of Yonsei University College of Medicine from January 2000 to December 2006. Methylation of interest loci was confirmed using pyrosequecning.The significant methylation frequencies (MtI > 5%) of the 3 gene analyzed were 17% for P16, 54% for DAPK, 60% for E-cadherin. P16 and DAPK MtI status correlated with perineural invasion and tumor depth, respectively. In 65 patients, the 3-year and 5-year overall survival was 54.9% and 48.4%, respectively. In multivariate analysis of overall survival, presence of lymph node metastasis and P16 methylation status were identified as an independent prognostic factors for overall survival. In patient with unmethylated of P16, the 3- and 6-yeat survival rates were 60.8 % and 54.9 %, respectively. In patients with a hypermethylated of P16, the 3- and 6-yeat survival rates were 27.3 % and 0.0 %, respectively. P16 hypermethylation can predict overall survival in curative resected mid/distal bile duct cancer. Classification of mid/distal bile duct cancer by both genetic and epigenetic profiles may improve the capability of predicting prognosis and of applying tailored therapy in mid/distal cancer.ope

Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts

Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell-CAF interaction in the CIPCO promoted epithelial-mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME.ope

An Ultrasonically Powered Implantable Microprobe for Electrolytic Ablation

Electrolytic ablation (EA) is a promising nonthermal tumor ablation technique that destroys malignant cells through induction of a locoregional pH change. EA is typically performed by inserting needle electrodes inside the tumor followed by application of direct current (DC), thus inducing electrolysis and creating localized pH changes around the electrodes. In this paper, we report an ultrasonically powered implantable EA microprobe that may increase the clinical relevance of EA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period). The wireless EA microprobe consists of a millimeter-sized piezoelectric ultrasonic receiver, a rectifier circuit, and a pair of platinum electrodes (overall size is 9x3x2mm(3)). Once implanted through a minimally invasive procedure, the microprobe can stay within a solid tumor and be repeatedly used as needed. Ultrasonic power allows for efficient power delivery to mm-scale devices implanted deep within soft tissues of the body. The microprobe is capable of producing a direct current of 90 mu A at a voltage of 5V across the electrodes under low-intensity ultrasound (similar to 200mW/cm(2)). The DC power creates acidic (pH12.9) regions around the anode and the cathode, respectively. The pH change, measured using tissue-mimicking agarose gel, extends to 0.8cm(3) in volume within an hour at an expansion rate of 0.5mm(3)/min. The microprobe-mediated EA ablative capability is demonstrated in vitro in cancer cells and ex vivo in mouse liver.ope

과기정통부와 산림청간의 차이 비교 분석

학위논문(석사) -- 서울대학교대학원 : 행정대학원 행정학과(행정학전공), 2023. 8. 김준기.The purpose of this study is to analyze the differences between Ministry of Science and ICT(MSIT) and Korea Forest Service(KFS) in terms of the factors that influence red tape. In modern administration, the red tape phenomenon is being discussed by many domestic and foreign scholars as a cause of policy failure from the people, who are consumers of administration, as well as hindering the productivity of public organizations. In particular, in the era of the Fourth Industrial Revolution represented by the VUCA (Volatile, Uncertain, Complex, and Ambiguous) environment, the effectiveness of bureaucracy as the source of red tape is gradually decreasing, and the concept of governance is emerging as an alternative to replace it. In particular, compared to private organizations, it is revealed that public organizations create more red tapes due to various factors such as goal ambiguity, formalization, centralization, audit, developmental culture, and information technology, and so on. Looking at many studies on red tape that have been done so far, red tape is used as independent variable, dependent variable, or moderate variable. In this study, red tape was treated as a dependent variable and literature review was conducted to find out the variables that affect it, which related to public administration, political science, psychology, sociology, and cultural anthropology. As a result of reviewing many literatures, it was found that a total of six factors affect the level of red tape. First, formalization and centralization variables as organizational structural factors are widely used as the independent variables. Second, as organizational behavioral factors, core values within the organization and symbolic formalism are used as independent variables. Third, as an information technology factor, the introduction of ICT technology appears to reduce red tape within organizations, but some studies claim that the performance is insignificant. Fourth, as a political factor, it is argued that the influence of the National Assembly, civic groups, and civic movement groups affect the level of red tape. Fifth, as an institutional factor, it is argued that institutions determine the level of red tape by influencing interactions between actors and their preferences. Typical examples are the total cap of regulation and active administration. Finally, in terms of an organizational culture, the level of red tape might decrease when a developmental culture environment is created rather than a hierarchical culture. A two-week survey was conducted from March 7 to 21 for MIST and KFS to see how the factors mentioned above actually affect the level of red tape. The analytic results can be summarized as follows. First, looking at the mean value and difference between groups (t-test), statistically significant variables at the 0.05 level were the red tape level, centralization, developmental culture, and information technology. Specifically, for the red tape, KFS (2.88) was higher than MIST (2.56), and MIST was higher than KFS in terms of developmental culture (MIST: 3.03, KFS: 2.82) and information technology (MIST: 3.39, KFS: 3.11), respectively. In terms of the research hypothesis, there were some significant differences between MIST and KFS in factors affecting red tape. There are a total of six research hypotheses set up in this study, and among them, four sub-hypotheses were established in relation to information technology and developmental culture, which are moderating variables. First, in the case of MIST, only the centralization variable as well as the interaction variable between formalization and developmental culture was found to be statistically significant at the 0.05 level. In other words, the higher the level of centralization among members of the organization was perceived, the higher the level of red tape was perceived. Concerning the interaction effect between formalization and developmental culture, the more complex an organization is, the higher the level of formalization is in general. When a high developmental culture is established, coupled with a high level of formalization, members of the organization rather perceive the level of red tape as low, compared with a low development culture. Conversely, in a low developmental culture, the higher the level of formalization, the higher members of the organization might recognize the formalization as red tape. As argued by DeHart-Davis (2009), a high developmental culture means that members of the organization perceive formalization as green tape rather than red tape. Second, in the case of KFS, the variables of centralization, audit, interaction between centralization and developmental culture, and interaction between audit and developmental culture were found to be statistically significant at the 0.05 level. In KFS, only the research hypothesis on centralization was adopted. Unlike MIST mainly concerned with policy planning, KFS as an external agency of MAFRA (Ministry of Agriculture, Food and Rural Affairs) mainly focuses on policy execution. For this reason, the level of centralization of KFS is higher than that of MIST. In the case of high centralization, the developmental culture is very important factor. According to the results of the KFS analysis, in the case of low developmental culture, high centralization leads organization members to perceive the level of red tape as higher than that of high developmental culture. In the case of high centralization, it suggests that creating a high developmental culture is very important. Another interesting thing is that in the low innovation culture, the awareness of the level of red tape is very wide according to the level of centralization, whereas in the high developmental culture, the awareness of the level of red tape is relatively narrow. However, looking at the interaction effect between audit and developmental culture, when a high developmental culture is dominant, the intensity of the red tape level felt by members of the organization according to the level of audit is much greater than in the case of a low developmental culture. This finding suggests that internal audits by organizational members themselves rather than external audits are more effective in lowering the level of red tape when organizational managers succeed to establish a high developmental culture. Taken the analytic results together, it can be seen that the variables affecting the red tape appear differently between MIST and KFS. The policy implications for administrative theorists and practitioners are as follows. First, strategies to reduce red tape should be used differently according to the characteristics of ministries. In other words, executive departments need to pay more attention to audit management than policy planning departments. Self-auditing for the members of the organization themselves can be much more effective than external auditing. Second, when the developmental culture is dominant, high control can greatly reduce organizational effectiveness by imprinting the seriousness of red tape on members more. Third, MIST, a policy planning department, needs to pay more attention to the formalization variable in managing red tape levels by organizational managers, and KFS, a policy enforcement department, needs to pay more attention to the centralization variable. However, both ministries need to pay special attention to creating a developmental culture within the organization in the era of the 4th industrial revolution represented by the VUCA environment. The limitations of this study are as follows. First, it is difficult to generalize the results of the study because only two of the 46 central ministries were targeted. If more studies on the central government are done in the future, it is necessary to conduct a meta-analysis by synthesizing them. Second, there is a limit to understanding the influence of dynamic variables over time because only one time point was targeted. To overcome this, it is necessary to conduct time series analysis using panel data. Third, it is necessary to examine in depth how the independent variables that affect the level of red tape appear differently between power ministries and non-power ministries, and what differences exist in the influence of moderating variables. Lastly, although this study targeted only the central government, it is also important to expand the scope of the research and conduct a comparative analysis targeting public institutions, government-invested institutions, and private companies. Because regulation vs. market debate is an important topic in the field of public administration, it is very meaningful to identify where the problem of red tape is the most serious among these fields.본 연구의 목적은 과기정통부와 산림청의 레드테이프에 영향을 미치는 요인의 차이를 분석하는 것이다. 현대행정에 있어 레드테이프 현상은 행정조직의 생산성을 저해할 뿐만 아니라 행정 수요자인 국민들로부터 정책실패를 야기하는 원인으로 많은 국내외 학자들에 의하여 거론되고 있다. 특히 VUCA(Volatile, Uncertain, Complex, and Ambiguous) 환경으로 대변되는 4차 산업혁명시대에 있어 레드테이프의 근원인 관료제의 효용성은 점점 더 감소하고 있으며, 이를 대체하기 위해 거버넌스 개념이 대안으로 부상하고 있다. 특히 민간조직에 비해, 공공조직은 목표 모호성, 공식화, 집권화, 감사, 혁신문화, 정보기술 등 다양한 요인에 의해서 더 많은 레드테이프를 만들어 내는 것으로 밝혀지고 있다. 그동안에 이루어진 레드테이프에 관한 많은 연구들을 보면, 레드테이프를 독립변수, 종속변수, 혹은 조절매개변수로 사용하고 있다. 이번 연구에서는 레드테이프를 종속변수로 취급하고 여기에 영향을 미치는 변수들을 찾아내기 위해 행정학, 정치학, 심리학, 사회학, 문화인류학과 관련된 문헌들을 심층적으로 검토하였다. 기존 문헌들을 검토한 결과, 총 6가지 요인들이 레드테이프 수준에 중요한 영향을 미치는 것으로 나타났다. 첫째, 조직 구조적 요인으로서 이의 특성을 가늠해 주는 요소인 복잡성. 공식화, 집권화 변수가 독립변수로서 많이 사용되고 있다. 둘째, 조직 행태적 요인으로서 조직 내 핵심가치, 상징적 형식주의 등이 독립변수로서 활용되고 있다. 셋째, 정보 기술적 요인으로서 ICT 기술의 도입이 조직 내 레드테이프를 줄이는 것으로 나타나고 있으나 일부 연구는 그 성과가 미미하다고 주장한다. 넷째, 정치적 요인으로서 국회, 시민단체, 시민사회단체, 시민운동단체들의 영향력이 레드테이프 수준에 영향을 미친다고 주장한다. 다섯째, 제도적 요인으로서 제도는 행위자 간 상호작용의 역할 및 행위자 선호에 영향을 미침으로써 레드테이프 수준을 결정한다고 주장한다. 대표적인 제도로 규제총량제와 적극행정의 적극적 도입이 있다. 마지막으로 조직 문화적 요인이 있는데 레드테이프는 위계 문화보다는 혁신 문화 환경이 조성될 때 그 수준이 감소한다고 보는 것이 일반적이다. 위에서 언급된 요인들이 레드테이프 수준에 실제 어떤 영향을 미치는지를 과기정통부(MIST)와 산림청(KFS)을 대상으로 3월 7일부터 21일까지 2주간 구조화된 설문지를 활용해 서베이를 실시하였다. 본 연구를 통해 도출된 분석결과를 요약해 보면 다음과 같 다. 첫째, 집단 간 평균차이 검증(t 검증)을 보면, 유의수준 0.05에서 통계적으로 유의미한 변수는 종속변수인 레드테이프 수준과 독립변수인 집권화, 혁신문화, 정보기술로 나타났다. 구체적으로 보면, 레드테이프 수준의 평균값은 KFS(2.88)가 MIST(2.56)보다 높았고 혁신문화(MIST: 3.03, KFS: 2.82)와 정보기술(MIST: 3.39, KFS: 3.11) 수준은 각각 MIST가 KFS보다 높았다. 연구가설에서 설정한 것처럼 MIST와 KFS 간에 레드테이프에 영향을 미치는 요인들에서 상당한 차이가 나타났다. 이번 논문에서 설정한 연구가설은 총 6개이며, 그 중 조절변수인 정보기술과 혁신문화와 관련하여 각각 4개의 하위가설이 설정되었다(4개의 하위가설은 독립변수인 목표 모호성, 공식화, 집권화, 감사와 두 개의 조절변수인 혁신문화와 정보기술 간의 상호작용항임). 첫째, MIST의 경우엔 집권화 변수와 공식화와 혁신문화 간 상호작용항 변수만이 유의수준 0.05에서 통계학적으로 유의미한 것으로 나타났다. 즉, 연구가설에서 설정한 것처럼 조직 내 구성원들이 집권화 수준을 높게 인식할수록, 레드테이프 수준도 높게 인식하는 것으로 나타났다. 그리고 공식화와 혁신문화 간 상호작용항의 분석결과를 보면, 조직이 복잡해질수록 공식화 수준은 일반적으로 높아지는데, 높은 혁신문화가 자리잡게 되면 높은 공식화 수준에서도 조직 구성원들은 오히려 레드테이프 수준을 낮게 인식한다는 것은 흥미로운 발견이었다. 반대로 낮은 혁신문화일 때는 공식화 수준이 높으면 높을수록 조직 구성원들은 이를 레드테이프로 인식할 가능성이 높아진다는 것이다. DeHart-Davis(2009)의 주장대로, 높은 혁신문화에서는 조직 구성원들이 공식화를 레드테이프가 아니라 그린테이프로 인식하게 된다는 것을 시사해 주고 있다. 둘째, KFS의 경우엔 집권화, 감사 요인, 집권화와 혁신문화 간 상호작용, 감사와 혁신문화 간 상호작용 변수가 유의수준 0.05에서 통계학적으로 유의미한 것으로 나타났다. KFS에 있어서는 집권화에 관한 연구가설만이 채택되었다. 즉, 정책기획업무가 주된 업무인 MIST와는 달리, MAFRA(Ministry of Agriculture, Food and Rural Affairs)의 외청인 KFS는 주로 정책집행업무에 치중해 있다. 이러한 이유로 MIST에 비해 KFS의 집권화 수준이 높게 나타나고 있다. 높은 집권화일 때 혁신문화 수준의 높·낮음이 매우 중요한데, KFS에 대한 분석결과를 보면 낮은 혁신문화일 때에 높은 집권화는 조직 구성원들로 하여금 레드테이프 수준을 높은 혁신문화에 비해 더 높게 인식하고 있는 것으로 나타났다. 따라서 높은 집권화 현상이 조직 내에 지배적일 경우에는 높은 혁신문화 조성이 매우 중요하다는 것을 시사해 주고 있다. 또 하나 흥미로운 점은 낮은 혁신문화에서는 조직 구성원들이 집권화 수준의 인식 정도에 따라 레드테이프 수준에 대한 인식 폭의 차이가 매우 큰데 비하여 높은 혁신문화에서는 상대적으로 레드테이프 수준에 대해 느끼는 인식의 폭이 적다는 점이다. 하지만 감사와 혁신문화 간 상호작용 효과를 보면, 높은 혁신문화가 지배적일 때 감사 수준의 높·낮음에 따라 조직 구성원들이 느끼는 레드테이프 수준의 폭이 낮은 혁신문화일 때 비해 훨씬 더 크다는 것이다. 이러한 발견은 조직관리자로 하여금 높은 혁신문화가 자리 잡을수록 외부 감사보다는 조직 구성원들 스스로에 의한 자율감사가 레드테이프 수준을 낮추는데 효과적이라는 점을 시사해 주고 있다. 지금까지의 분석결과를 종합해 보면, 정책기획업무를 주로 하는 MIST와 집행업무가 주된 업무인 KFS 간에는 레드테이프에 영향을 미치는 변수가 다르게 나타남을 알 수 있다. 이러한 분석결과가 행정이론가나 실무자들에게 주는 정책적 함의는 다음과 같다. 첫째, 부처의 특성에 따라 레드테이프를 줄이기 위한 전략은 다르게 구사되어야 한다. 즉, 집행부처인 경우에 감사 수준의 관리에 정책기획부처보다 더 많은 관심을 기울일 필요가 있다. 과도한 감사보다는 조직 구성원 스스로에 위한 자율감사가 훨씬 더 효과적일 수 있다. 둘째, 혁신문화가 지배적일 때는 과도한 감사는 레드테이프에 대한 심각성을 구성원들에게 더 많이 각인시켜 조직효과성을 크게 떨어뜨릴 수 있다. 셋째, 정책기획부처인 MIST는 조직 관리자가 레드테이프 수준을 관리하는데 있어 공식화 변수에 좀 더 많은 관심을 가질 필요가 있고 정책집행부처인 KFS는 집권화 변수에 좀 더 많은 관심을 기울일 필요가 있다. 하지만 두 부처 모두 VUCA환경으로 대변되는 4차 산업혁명 시대를 맞아 조직 내 혁신문화 조성에 각별히 관심을 기울일 필요가 있다. 이번 연구가 가지는 연구의 한계점은 다음과 같다. 첫째, 46개 중앙부처 중 두 개 부처만을 대상으로 했기 때문에 연구 결과를 일반화하기는 어렵다. 앞으로 중앙부처에 대한 더 많은 연구가 이루어지면 이를 종합하여 메타 분석을 해 볼 필요가 있다. 둘째, 한 시점만을 대상으로 했기 때문에 시간적 흐름에 따른 동태적 변수의 영향을 파악하는 데는 한계가 있다. 이를 극복하기 위해서는 패널 데이터를 활용한 시계열 분석이 이루어질 필요가 있다. 셋째, 권력부처와 비권력부처 간에 레드테이프 수준에 영향을 미치는 독립변수가 어떻게 상이하게 나타나고 있는지, 조절변수의 영향력에서는 어떠한 차이가 있는지를 심도 있게 규명할 필요가 있다. 끝으로, 이번 연구는 중앙부처만을 대상으로 했지만, 연구범위를 확대하여 공공기관, 정부투자기관, 민간 기업을 대상으로 한 비교분석을 해 보는 것도 중요하다. 왜냐하면 규제 vs 시장 논쟁은 행정학 분야의 중요 화두이기 때문에 레드테이프의 문제가 이들 부문 중에서 어느 곳에서 가장 심각한지를 규명해 보는 것은 매우 의미가 있다고 생각된다.제 1 장 서론 1 제 1 절 연구목적 1 제 2 절 연구의 범위 및 방법 3 제 2 장 이론적 논의 및 선행연구 검토 5 제 1 절 레드테이프 개념 및 의의 5 1. 개념 5 2. 의의 및 유형 5 제 2 절 레드테이프 발생 원인으로서의 관료제 논의 6 1. 관료제 개념과 주요 특성들 6 2. 관료제 조직구조의 구성 차원 8 3. 그린테이프 vs 레드테이프 8 4. 레드테이프 감축을 위한 민첩한 정부 13 제 3 절 레드테이프 영향요인들 13 1. 조직 구조적 요인 13 2. 조직 행태적 요인 14 3. 정보 기술적 요인 16 4. 정치적 요인 16 5. 제도적 요인 17 6. 조직문화 요인 18 제 4 절 선행연구 동향 및 논의 19 1. 공·사조직 간 및 업무특성에 따른 레드테이프 차이 연구 19 2. 레드테이프 원인변수에 대한 연구 21 3. 레드테이프의 실제 사례들 23 제 3 장 연구모형 및 연구방법 26 제 1 절 연구모형 설정 26 제 2 절 연구방법 26 1. 변수의 조작화 및 측정 26 2. 확인적 요인분석 및 신뢰도 검증 28 3. 연구가설 설정 30 제 4 장 분석결과 및 논의 33 제 1 절 표본 대상의 특성 33 제 2 절 통계분석 결과 및 논의 34 1. 기술통계 분석 및 집단 간 차이 검증 34 2. 상관관계 분석 36 3. 다중회귀 분석 37 제 5 장 정책적 함의 및 결론 52 제 1 절 정책적 함의 52 1. 조직 구조적 측면 52 2. 조직 행태적 측면 53 3. 정보 기술적 측면 54 4. 정치적 측면 55 5. 조직 문화적 측면 56 6. 제도적 측면 56 제 2 절 요약 및 연구한계 57 참고문헌 59 부록 65석

Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone

Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.ope

Intraductal papillary mucinous neoplasm of the biliary tract with cardiac metastasis: A case report

Introduction: Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later. Patient concerns: A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital. Diagnosis: Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion. Interventions: Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy. Outcomes: Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed. Conclusion: To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB.ope

Surgical Management of Chronic pancreatitis: What Can Surgeons Do?

Chronic pancreatitis (CP) is an inflammatory disease and causes chronic pain, exocrine and endocrine function failure. Pain is major indication for surgical procedure indication in CP. Advances in noninvasive treatment now allow for better therapeutic options at an early stage of CP. However, many data show that surgical procedure may produce superior results to endoscopic treatment in CP management. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. There are many surgical options to control chronic pain in CP, therefore preoperative assessment is important to choose optimal surgical management. Effective surgical procedures and timing of surgery for chronic pancreatitis remain unclear. This review comprehensively assesses the evidence for these different approaches to surgical intervention in chronic pancreatitis.ope