Subjectivity at Different Stages in the Contracting Process

학위논문 (석사)-- 서울대학교 대학원 : 경영학과 회계학 전공, 2013. 2. 신재용.When considering the overall contracting process, subjectivity can be adopted in the contract design stage and/or the performance evaluation stage of the contracting process. By distinguishing between these two different contracting stages I shed light on the differential incentives for the inclusion of subjective performance measures at the different stages of the contracting process. My results show that in the contract design stage less subjective performance measures are included in the contract when the compensation committee is unlikely to formulate sufficient subjective assessments due to inadequate knowledge of the to-be-evaluated CEOs and when the level of trust between the compensation committee and the CEO is low. In the performance evaluation stage, after performance results based on objective measures are readily available, subjectivity tends to be used more as a potential tool to complement the predetermined contract. In particular, in cases where the predetermined contract did not assign high weights to objective performance measures that the CEO was able to significantly outperform, my analyses suggest that subjectivity was applied in order to account for such effects ex-post. My last set of hypotheses tries to investigate whether subjectivity is used as a potential tool for powerful CEOs to extract rent. Consistent with prior literature, the mere use of subjectivity in evaluating powerful CEOs does not lead to excess compensation. However, I find that powerful CEOs take advantage of performance evaluators outcome biases and spillover effects from the determined performance results based on objective measures to extract greater amounts of compensation.1. INTRODUCTION 2. PRIOR LITERATURE 3. HYPOTHESES DEVELOPMENT 3.1. Subjectivity in the Contract Design Stage 3.2. Subjectivity in the Performance Evaluation Stage 3.3. Subjectivity as a Potential Tool for Rent Extraction 4. SAMPLE SELECTION AND VARIABLE MEASUREMENT 5. RESEARCH DESIGN AND EMPIRICAL RESULTS 5.1. Subjectivity in the Contract Design Stage 5.2. Subjectivity in the Performance Evaluation Stage 5.3. Subjectivty as a Potential Tool for Rent Extraction 6. SUMMARY AND CONCLUSIONMaste

Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells

Many osteopenic disorders, including a postmenopausal osteoporosis and lytic bone metastasis in breast and prostate cancers, are linked with a hyperosteoclast activity due to increased receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblastic/stromal cells. Therefore, inhibition of RANKL-induced osteoclastogenesis and osteoclast-induced bone resorption is an important approach in controlling pathophysiology of these skeletal diseases. We found that, of seven type I, II, and III saikosaponins isolated from Bupleurum falcatum, saikosaponins A and D, type I saikosaponins with an allyl oxide linkage between position 13 and 28 and two carbohydrate chains that are directly attached to the hydroxyl groups in position 3, exhibited the most potent inhibition on RANKL-induced osteoclast formation at noncytotoxic concentrations. The stereochemistry of the hydroxyl group at C16 did not affect their activity. Saikosaponins A and D inhibited the formation of resorptive pits by reducing the secreted levels of matrix metalloproteinase- (MMP-) 2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Additionally, saikosaponins A and D inhibited mRNA expression of parathyroid hormone-related protein as well as cell viability and invasion in metastatic human breast cancer cells. Thus, saikosaponins A and D can serve as a beneficial agent for the prevention and treatment of osteoporosis and cancer-induced bone loss.ope

Museum of science and art : frank oppenheimer and the early history of the exploratorium

학위논문 (석사)-- 서울대학교 대학원 : 협동과정 과학사및과학철학전공, 2011.2. 홍성욱.Maste

과학 영재와 일반 학생의 창의성 비교 연구 : 확산적 사고와 과학 창의성을 중심으로

학위논문(석사)--서울대학교 대학원 :과학교육과 지구과학전공,2002.Maste

Optimal designs for mixture experiments with process variables

Thesis(master`s)--서울대학교 대학원 :통계학과,2004.Maste

분화 및 미분화 상태의 치은상피세포에서 패턴인식수용체 발현

학위논문(석사) --서울대학교 대학원 :치의학과,2008.2.Maste

Studies on bradykinin signaling pathway in sensory neurons 감각신경 세포에서 브라디키닌의 신호전달 체계에 관한 연구

Thesis (doctoral)--서울대학교 대학원 :약학과 약물학전공,2002.Docto

치주염관련 구강 세균 Fusobacterium nucleatum 및 Treponema denticola에 대한 치은상피세포와

Background Periodontitis is a chronic inflammatory disease caused by polymicrobial infection and subsequent host immune responses. Bacterial colonization in the gingival sulcus is an initial step in the establishment of infection. Gingival epithelia are in the closest contact with those colonized bacteria constantly and provide physical and chemical barrier. Gingival epithelial cells recognize bacteria through pattern recognition receptors and struggle to eliminate the bacteria by producing anti-microbial peptides (AMPs). However, some pathogens often subvert or down-regulate the defense mechanisms. In addition, periodontal pathogens often invade gingival epithelial cells and also survive within the cells. Consequently, this persistent infection induces chronic inflammation. Among the oral bacteria, Fusobacterium nucleatum is a potent immune activator that induces AMPs and IL-8 from gingival epithelial cells. On the other hand, Treponema denticola, one of major pathogens involved in periodontitis, inhibits the expression of AMPs and IL-8 from gingival epithelial cells. T. denticola can evade the innate immunity therefore appropriate adaptive immunities require to defenses it. To understand the pathogenesis of periodontitis, four questions were addressed in this study. First, the molecular mechanisms involved in the suppression of AMPs by T. denticola in gingival epithelial HOK-16B cells were studies. Second, intracellular destiny of T. denticola within HOK-16B cells were studies. Third, the effects of co-infection with F. nucleatum and T. denticola were investigated. Fourth, antibody and T-cell mediate responses to T. denticola and F. nucleatum were characterized in healthy subjects and periodontitis patients. Materials and methods To identify the molecular mechanisms involved in the suppression of human beta defensins (HBDs) in human gingival epithelial cells, immortalized or normal human gingival epithelial cells were infected with live or heat-killed T. denticola for 24 h, and the expression of HBDs was examined by real time RT-PCR. Knockdown of Toll like receptor 2 by RNA interference (RNAi) and neutralization of TNFα with anti-TNFα antibody were performed in gingival epithelial HOK-16B cells. Activation of signaling pathways that are known to regulate HBDs and IL-8, was examined by an enzyme-linked immunosorbent assay (ELISA). To examine the invasion of T. denticola into gingival epithelial cells, HOK-16B cells were infected with 5- (and 6-) carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labeled live or heat-killed T. denticola for 24 h, and the presence of bacteria inside cells was confirmed by confocal microscopy. The invasive ability was quantified by flow cytometry. To determine the destiny of internalized T. denticola, co-localization with early endosomes and lysosomes was examined under the confocal microscopy. Subcellular localization of bacteria was examined under the transmission electron microscopy. Intracellular survival of T. denticola was examined by antibiotics protection assay. To characterize the bacteria-specific T cell and Ab response, blood samples were obtained from patients with aggressive periodontitis (n=10), with chronic periodontitis (n=11), and their age- and sex-matched healthy controls (n=21). Saliva was also obtained from patients with chronic periodontitis and their controls. After clinical treatments of patients with chronic periodontitis (n=9), saliva and blood were re-sampled. The levels of bacteria-specific IgA, IgG1, and IgG4 in plasma and that of IgA in saliva were quantified by ELISA using recombinant FADA and Td92, a surface antigen of F. nucleatum and T. denticola, respectively. The levels of F. nucleatum and T. denticola in dental plaque or precipitate from saliva were analyzed by real time PCR. Peripheral mononuclear cells (PBMCs) were stimulated with FADA or Td92. Then, the number of Ag-specific CD4- and Treg cells was examined by flow cytometry using CD154+ and FOXP3+ as a marker, respectively. In addition, the amounts of secreted IL-4, IL-10, IL-17, and IFNγ were analyzed by ELISA. Results Live T. denticola suppressed the expression of HBD-2 and -3 about 50% and reduced the activation of JNK and NF-κB. However, heat-killed bacteria did not present such suppressive effect and rather up regulated the level of HBD-2 and 3. T. denticola infection could rapidly suppress the expression of HBD-3 from 1h of infection. However, HBD-2 expression suppressed only at late time points, which was accompanied with the suppression of TNFα production. Neutralization of TNFα with an antibody abrogated the suppressive effect of T. denticola on HBD-2. In addition, heat-killed T. denticola did not suppress TNFα production. Knockdown of TLR2 by RNA interference reversed the suppressive effect of T. denticola on the expression of HBD-2 and -3 but not on the production of TNFα. Furthermore, live T. denticola had ability to inhibit TLR2 activation by Pam3CSK, which disappeared by the treatment of heat or proteinase K. In conclusion, T. denticola suppressed the expression of HBDs in gingival epithelial cells by inhibiting ether TLR2 activation and TNFα production. Live T. denticola, but not heat-killed bacteria, invaded HOK-16B cells. Confocal microscopy also revealed that internalized T. denticola rarely colocalized with either endosomes or lysosomes. Transmission electron microscopy of infected cells showed that intracellular T. denticola was localized inside endosome-like structures tightly enclosed vesicles or vacuoles, and the proportion of bacteria localized to vacuoles increased after culturing for an additional 24 h. Although a culture-based antibiotics protection assay suggested that intracellular T. denticola dies within 12 h of infection, a substantial number of bacteria were observed by confocal microscopy up to 48 h after infection. In addition, flow cytometric analysis of HOK-16B cells infected with CFSE-labeled T. denticola showed that there was no loss of fluorescence over 48 h. Co-infection of T. denticola and F. nucleatum increased the invasive ability of T. denticola and rendered F. nucleatum to resist endocytic degradation. In addition, this co-infection neutralized the ability of F. nucleatum and T. denticola to induce or suppress HBDs but suppressed the expression of IL-8. In healthy individuals, higher levels of plasma IgG1 and salivary IgA to FADA than those to Td92 were observed. Compared with healthy subjects, patients with aggressive periodontitis showed significantly decreased levels of FADA-specific-IgA and -IgG1, and Td92-specific-IgA in plasma. However, the patients with chronic periodontitis did not show any significant difference in the levels of bacteria-specific Abs in plasma or in saliva. PBMCs from healthy individuals significantly increased the number of CD154+ CD4 T cells following in vitro stimulation with either FADA or Td92. In addition, both Ags enhanced IL-10 and IFNγ but decreased IL-4 secretion. Such bacterial Ag-induced upregulation of IFNγ did not observed in patients with chronic periodontitis. In addition, the PBMCs from the chronic periodontitis patients produced the higher level of IL-4 than those from healthy controls in the basal level and also following stimulation with either FADA or Td92. Interestingly, these decreased IFNγ and increased IL-4 responses to FADA and Td92 were exaggerated after clinical treatment. Conclusion T. denticola suppresses the expression of HBD-2 and -3 in gingival epithelial cells by inhibiting TLR2 activation and TNFα production. In addition, T. denticola not only invades gingival epithelial cells but also survive within the host cells for an extensive number of hours through evading from endocytic degradation pathway. Simultaneous colonization by F. nucleatum and T. denticola is expected to aggravate the pathogenicity of each bacterium. In healthy individuals, F. nucleatum and T. denticola induce Th1 (IgG1 and IFNγ)- and Tr1 (IgA and IL-10)-dominant immune responses. Impaired Ab and T cell responses were examined in patients with periodontitis.목 적 치주염은 복합 세균 감염에 대한 숙주 면역반응의 상호작용으로 치주조직의 파괴와 치아 상실을 유발하는 만성 염증성 질환이다. 수 많은 세균들이 치은 연하에 집락을 형성하게 되면서 감염이 확립되고 치은상피세포는 세균집락과 가장 가깝게 항시적으로 상호작용을 하고 있다. 치은상피세포는 패턴인식수용체를 통해 세균을 인지하고 항균물질이나 케모카인, 싸이토카인 등의 분비를 통해 선천면역을 유도하여 세균을 제거한다. 그러나 일부의 병원성 세균들은 이러한 선천면역반응을 억제하거나 회피한다. 또한 병원성 세균들은 상피세포를 침범할 뿐 아니라 세포 내에서의 생존을 통해 만성 염증 반응을 유도하게 된다. 수 많은 구강 세균 중 Fusobacterium nucleatum은 치은상피세포로부터 항균물질이나 케모카인 IL-8 분비를 강력하게 활성화 시키며 상피세포로 침투하는 능력이 높지만 세포 내에서 생존하지는 못한다. 반면 Treponema denticola는 상피세포로부터 항균물질이나 IL-8 발현을 억제하며 상피세포로 침윤이 가능하다. 이처럼 T. denticola는 선천면역으로부터 회피할 수 있으므로 T. denticola를 제어하기 위한 적절한 적응면역반응이 필요하다. 치주염의 병인을 이해하기 위해 다음과 같은 연구를 진행하였다. 첫째, T. denticola에 의한 치은상피 HOK-16B 세포의 항균물질 억제에 관련된 분자기전을 연구하였다. 둘째, T. denticola의 치은상피세포 내 운명을 연구 하였다. 셋째, T. denticola와 F. nucleatum의 동시 감염에 대한 치은상피의 면역반응을 연구하였다. 넷째, T. denticola와 F. nucleatum 특이적 항체 및 T 세포 면역반응의 특성을 건강인과 치주질환자에게서 연구하였다. 방 법 세균에 의한 항생물질의 발현 조절에 연루된 분자 기전을 밝히기 위해 치은상피세포의 Toll like receptor 2 발현을 RNA interference로 억제하거나 TNFα 기능을 항체 중화 방법으로 억제한 후 세균에 대한 치은상피세포의 항생물질 발현과 케모카인, 사이토카인의 발현을 실시간 유전자 증폭 및 효소 면역측정법을 통해 측정하였다. 항균물질과 IL-8 조절에 관련된 신호조절 분자들의 활성을 효소 면역측정법으로 측정하였다. 치은상피세포로 세균의 침투와 침투 후 운명을 관찰하기 위해 세균을 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE)로 염색한 후 세포로의 침투 능력을 유세포 분석기와 공초점형광현미경을 통해 관찰하였다. 세포로 침투 후 엔도좀, 라이소좀과의 결합을 공초점형광현미경을 통해 관찰하였으며 전자현미경을 통해 세포 내 세균의 위치를 관찰하였다. 항생제 보호 분석을 통해 세균의 세포 내 생존능력을 확인하였다. 배양접시에서 응집된 F. nucleatum과 T. denticola 감염 후 세포로의 침입 능력을 유세포 분석기로 확인하였으며 라이소좀과의 결합, 세포 내 생존능력, 치은상피세포에 의한 항균물질과 IL-8 발현 측정을 통해 두 세균의 공동 감염이 세균의 운명과 선천면역반응에 미치는 영향을 확인하였다. 세균 특이적 항체 및 CD4+ T 세포 면역반응을 확인하기 위해 정상인 (n=21)과 만성 (n=11) 또는 급성 (n=10) 치주질환자로부터 말초혈액과 치태 또는 타액을 얻었으며 만성 치주질환자의 경우 치료 후에 재 채취 하였다. 혈액으로부터 분리된 혈장에서 세균 특이적 IgA, IgG1, IgG4 항체를 타액의 상층액에서 IgA 항체를 효소 면역측정법으로 정량 하였다. 치태나 타액의 침전물에서 추출한 DNA를 이용하여 F. nucleatum과 T. denticola의 상대적인 양을 실시간 유전자 증폭을 통해 정량 하였다. 혈액에서 분리한 말초혈액 단핵구를 F. nucleatum과 T. denticola의 표면항원 재조합 단백질 FADA와 Td92로 자극시킨 후 항원 특이적 CD4+와 조절 T 세포 (Treg)의 수를 CD154+와 FOXP3+ 특이적 표지인자를 사용하여 유세포 분석기로 분석하였다. 또한 항원에 대한 반응으로 말초혈액 단핵구가 분비하는 IFNγ, IL-4, IL-10, IL-17을 효소 면역측정법을 통해 측정하였다. 결 과 첫째, T. denticola는 항균물질 Human beta defensin (HBD)-2와 -3의 발현을 억제하고 JNK와 NF-κB의 활성을 억제한다. 그러나 열처리 세균의 경우 HBD-2와 -3의 발현이 오히려 증가되는 것을 확인하였다. T. denticola는 HBD-3를 감염 1시간부터 억제하기 시작하였지만 HBD-2의 경우 감염 후 늦은 시간대에서 억제되었으며 TNFα 생산 감소를 동반하였다. 항체를 이용한 TNFα의 중화는 HBD-2의 억제 효과를 사라지게 하였다. 더욱이 열처리 세균은 TNFα를 감소시키지 못하였다. T. denticola에 의한 HBD-2와 -3의 억제 효과는 RNA 간섭을 통한 TLR2 발현 감소에 의해 사라졌지만 TNFα의 생산에는 영향이 없었다. 더욱이 살아있는 T. denticola는 Pam3CSK에 의해 유도된 TLR2의 활성을 억제시켰으며 열처리에 의해 사라졌다. 살아있는 T. denticola만이 HOK-16B 세포를 침투할 수 있었다. HOK-16B 세포 내로 침입한 T. denticola는 엔도좀이나 라이소좀과의 결합이 거의 일어나지 않았다. 세포 내로 침입한 T. denticola는 소낭이나 액포에 둘러 싸여져 있었으며 24 시간 추가 배양 후에는 세포 내 T. denticola가 액포에 더 많이 존재하는 것을 확인하였다. 비록 배양방법을 기본으로 한 항생제 보호 분석에서는 감염 후 12 시간 까지만 세균이 생존 하는 결과를 얻었지만 감염 후 48 시간 후에도 세포 내에 존재 하고 있는 것을 공초점형광현미경을 통해 관찰하였다. 더욱이 세포 내 CFSE-T. denticola의 형광이 48 시간 이후에도 감소되지 않는 것을 유세포 분석방법을 통해 확인하였다. T. denticola와 F. nucleatum의 동시 감염은 HOK-16B세포로의 T. denticola의 침윤능력을 증가시켰으며 F. nucleatum이 세포 내에서 분해되는 것을 감소시켰다. 더욱이, 동시 감염은 F. nucleatum과 T. denticola의 HBDs 발현유도 또는 억제 능력을 중화시켰으나 IL-8의 발현은 동시 감염에도 여전히 억제되어 있었다. 건강인은 FADA에 대한 혈장 IgG1과 타액 IgA가 Td92에 대한 항체보다 높은 것을 관찰하였다. 건강인과 비교하여 급성 치주염 환자의 경우 FADA-특이적-혈장 IgA, IgG1 그리고 Td92-특이적-혈장 IgA가 현저하게 감소되어 있다. 그러나 만성 치주염 환자들에 있어서는 세균-특이적 혈장이나 타액 항체의 변화가 관찰되지 않았다. 건강인의 말초혈액 단핵구들은 두 세균에 특이적으로 CD154+CD4+ T 세포를 증가시켰다. 두 세균 항원은 IL-10이나 IFNγ의 생산을 증가시켰지만 IL-4는 감소시켰다. 게다가 건강인에 비해 만성 치주염 환자는 IL-4의 생산량이 증가되어져 있었다. 흥미롭게도 임상적 치료 후에 FADA와 Td92에 대한 IFNγ의 감소와 IL-4의 증가가 관찰되었다. 결 론 T. denticola는 TLR2의 활성을 억제하거나 TNFα 생산의 억제를 통해 치은상피세포에서 HBD-2와 –3를 감소 시켰다. T. denticola는 치은상피세포로 침윤 후 엔도좀, 라이소좀과의 결합 회피를 통해 세포 내에서 생존하며 F. nucleatum과의 동시 감염은 두 세균의 병독력을 증가시켰다. 건강인은 F. nucleatum과 T. denticola 특이적 Th1 (IgG1, IFNγ)-과 TR1- 우세 면역반응을 유도하였다. 그러나 치주질환자들은 항체나 T 세포 면역반응이 감소되어 있었다.Docto

Science teacher's role for cultivating student's scientific creativity in the classroom

학위논문 (박사)-- 서울대학교 대학원 : 과학교육과(지구과학전공), 2011.8. 최승언.Docto

대두와 헤마토코쿠스 추출물 특정 비율 복합물의 자외선에 의한 광노화 개선 효능 규명

학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2016. 2. 이기원.Soybean has been constantly consumed in Asian countries. It contains high amounts of isoflavones. Soybean-derived isoflavones are known for many advantages such as anti-carcinogenic activity and estrogenic-like effect. In particular, soy isoflavones have been studied on their beneficial effects in improving UV-induced skin damage such as wrinkle formation and inflammation by binding with specific targets which result in regulating signal transduction. Haematococcus pluvialis (H. pluvialis, Haematococcus) is a carotenoid pigment containing the largest amount of natural astaxanthin. The astaxanthin is a non-provitamin A carotenoid, but it involves in retinoic acid receptor (RAR) or retinoid signaling which are associated with inhibiting activator protein (AP)-1 dependent transcription. Based on the previous studies, I hypothesized that soy extract (SE) and haematococcus extract (HE) can effectively improve UVB-induced photo-aging through specific signaling pathways by regulating targets. And I investigated an effect of the mixture in different ratios on UVB-induced wrinkles in hairless mice and human dermal fibroblasts (HDFs). The 1:2 ratio of SE and HE mixture (SHM) showed the most promising benefit compared to the other different ratios in vivo. Based on in vivo study I used primary HDFs for mechanisms study. SHM has an inhibitory effect on wrinkle formation through down-regulating matrix metalloproteinase (MMP)-1 protein and mRNA expression. SHM also inhibits transactivation of AP-1 which has important role in regulating MMP expression. In addition, SHM influences UVB-induced mitogen activated protein kinases (MAPKs) which regulate AP-1 transactivation. These result suggest that SHM could be a potential agent against UVB-induced skin wrinkles.Ⅰ. INTRODUCTION 1 Ⅱ. MATERIALS AND METHODS 8 1. Chemicals and reagents 8 2. Sample preparation 9 3. Animals and treatments 10 4. Cell Culture and treatments 12 5. Cell viability 13 6. Determination of winkle formation 14 7. Hematoxyln and eosin staining 15 8. Massons trichrome staining 15 9. Western blot and zymography 16 10. Real-time quantitative PCR 18 11. Luciferase reporter gene assay 20 12. Statistical analysis 21 Ⅲ. RESULTS 23 1. Oral administration of SHM decreased UVB-induced skin wrinkles in hairless mice 23 2. SHM prevented UVB-induced increase of epidermal thickness and collagen degradation in hairless mice 26 3. SHM significantly decreased UVB-induced MMP-1 overexpression in protein and gene level in cultured primary human dermal fbroblasts 29 4. SHM significantly decreased UVB-induced AP-1 trans-activation and influenced UVB-induced cellular signal transduction in cultured primary human dermal fibroblasts 33 Ⅳ. DISCUSSION 37 Ⅴ. REFERENCES 41 Ⅵ. 국문 초록 46Maste