Lipid droplets and lipotoxicity during autophagy.

Lipid droplets (LDs) are neutral lipid storage organelles that provide a rapidly accessible source of fatty acids (FAs) for energy during periods of nutrient deprivation. Surprisingly, lipids released by the macroautophagic/autophagic breakdown of membranous organelles are packaged and stored in new LDs during periods of prolonged starvation. Why cells would store FAs during an energy crisis was unknown. In our recent study, we demonstrated that FAs released during MTORC1-regulated autophagy are selectively channeled by DGAT1 (diacylglycerol O-acyltransferase 1) into triacylglycerol (TAG)-rich LDs. These DGAT1-dependent LDs sequester FAs and prevent the accumulation of acylcarnitines, which otherwise directly disrupt mitochondrial integrity. Our findings establish LD biogenesis as a general cellular response to periods of high autophagic flux that provide a lipid buffering system to mitigate lipotoxic cellular damage

Transfer Control for Resilient End-to-End Transport

Residing between the network layer and the application layer, the transport layer exchanges application data using the services provided by the network. Given the unreliable nature of the underlying network, reliable data transfer has become one of the key requirements for those transport-layer protocols such as TCP. Studying the various mechanisms developed for TCP to increase the correctness of data transmission while fully utilizing the network's bandwidth provides us a strong background for our study and development of our own resilient end-to-end transport protocol. Given this motivation, in this thesis, we study the different TCP's error control and congestion control techniques by simulating them under different network scenarios using ns-3. For error control, we narrow our research to acknowledgement methods such as cumulative ACK - the traditional TCP's way of ACKing, SACK, NAK, and SNACK. The congestion control analysis covers some TCP variants including Tahoe, Reno, NewReno, Vegas, Westwood, Westwood+, and TCP SACK

The role of Benign Envy on Consumption - A Cross-Cultural Comparison in Social Networking Environment

Objectives This thesis aims to investigate benign envy and purchase intentions of social media users in different cultures. To achieve this, Finnish and Vietnamese of all ages, who engaged in social media usage were sampled. As they represent the less and more collectivist sides of consumers, the difference in collectivism is employed to examine the variations in purchase intentions across cultures. Summary Despite being known for its negative impacts on personal and social well-being, envy possesses a subtype called benign envy, which constructively affects sales and economic development. Additionally, compared to malicious envy, benign envy is more common in social media settings. As the number of social media users increases substantially, this positive side of envy becomes a promising aspect for businesses to exploit. Previous studies connect benign envy with the motivation to obtain the same virtue or goods owned by the advantaged party. It is thus hypothesized that this pattern remains valid in online contexts. Moreover, because the intensity of benign envy and the need to conform with social norms are positively correlated to collectivism, collectivist nations are expected to have higher purchase intentions than individualists. 206 participants were engaged through a questionnaire to draw answers for these propositions. While the results support the first argument, they reject the second one since the impacts of envy and collectivism on purchase intentions are independent. Conclusions It could be concluded from this research that benign envy, regardless of offline or online settings, enhances the incentive to obtain the good of the comparable other. Nevertheless, collectivism does not have a significant role in this relationship. Social comparison, on the contrary, could increase envy-related consumption

펜톡시필린과 토코페롤의 방사선 조사 백서 악골에서의 피질골량과 골질 증진에 대한 미세단층촬영 연구

학위논문(석사)--서울대학교 대학원 :치의학대학원 치의과학과,2019. 8. 김성민.연구 배경 및 연구 목적 두경부 악성 종양의 치료 있어 방사선 치료는 일차적으로 근치적 치료 요법, 수술적 치료의 보조적 요법, 항압 치료와 함께 하는 병용 요법 또는 절제 불가능한 경우 고식적 치료 요법으로 사용되고 있다. 최근에는 방사선 치료 기술이 발전함에 따라, 예상하지 못한 합병증들이 국소화되고 있다. 그러나, 여전히 환자들은 점막, 하방의 턱뼈, 타액선의 방사선에 대한 반응으로 고통을 받고 있으며, 그 중에 가장 특이할 만한 합병증은 하악의 방사선 골괴사증 (osteoradionecrosis, ORN)이다. 펜톡시필린 (pentoxifylline)과 토코페롤 (tocopherol)은 강력한 섬유화 방지 효과를 가지고 있으며, 이는 만성 섬유화를 감소시키고 ORN에서 골치유를 촉진시키는 것으로 알려져 왔다. 펜톡시필린과 토코페롤의 병용 요법은 수술적 치료에 보조적으로 또는 ORN의 비침습적 치료 방법으로 사용될 수 있다. 본 연구에서는 새로운 micro-CT 패러다임을 사용하여 ORN 동물 모델에 펜톡시필린과 토코페롤을 투여하여 약제의 효과를 피질골 분석을 통해 평가하고, 이를 바탕으로 ORN의 병태생리 및 최근의 치료법에 대하여 논의할 것이다. 연구 방법 8주령의 평균 몸무게 369.6g인 수컷 Sprague-Dawley 백서 (오리엔트바이오, 성남, 한국) 48마리를 실험에 사용하였다. 백서는 무작위로 실험군으로 방사선 조사군 (40 마리)과 대조군으로 방사선 조사를 받지 않은 군 (8마리)으로 나누었다. 방사선 조사군은 투여한 약물에 따라서 PTX (펜톡시필린, pentoxifylline), TP (토코페롤, tocopherol), PTX+TP (펜톡시필린과 토코페롤, pentoxifylline and tocopherol)와 NS (생리 식염수, normal saline)로 나누었다. 약제는 실험 기간 종료시까지 투여하였다. 방사선 조사 3주 후에, 하악 구치의 발치를 진행하였다. 실험 동물은 방사선 조사 7주, 발치 4주 후에 희생하였다. 채취한 하악골은 micro-CT와 조직학적 평가를 통해 분석하였다. 연구 결과 1. Micro-CT 분석 방사선 조사군 중에 NS군과 대조군 (C)에서 치조골 높이 (alveolar bone height, ABH)와 피질골 두께 (cortical bone thickness, CBT)를 비교하였다. ABH와 CBT는NS군에서 방사선 비조사군 (C)에 비하여 낮게 나타났다. 방사선 조사 실험군에서 투여한 약제에 따라 ABH와 CBT를 비교하였다. 펜톡시필린과 토코페롤을 함께 투여한 군에서 ABH와 CBT는 다른 실험군에 비하여 유의미하게 높게 나타났다. PTX+TP군에서 ABH와 CBT는 유의미한 차이를 나타내지는 않았다. PTX 군에서 CBT는 NS 군에 비하여 유의미하게 높게 나타났다. (p < 0.05). 모든 방사선 조사군에서 설측의 치조골 소실 (ΔHL)이 협측의 치조골 소실 (ΔHB)에 비하여 유의미하게 높게 나타났다. 협측에서, PTX+TP를 사용한 그룹에서 PTX 그룹과 NS 그룹에 비하여 ΔHB가 유의미하게 낮게 나타났다. 설측에서는 NS 그룹의 ΔHL이 PTX + TP 그룹의 ΔHL에 비하여 유의미하게 높게 나타났다 (p < 0.05). 방사선 조사군 중 PTX + TP군에서 피질골 부피 (cortical bone volume, Ct.BV)와 총피질골 표면적 (Ct.S)이 PTX, TP, NS 군에 비하여 유의미하게 높게 나타났다. 총기공 부피 (total pore volume, Pov)은 약제에 따른 차이를 보이지는 않았다. 총기공 부피율 (total pore rate, PoV%)는 PTX + TP 군에서 PTX 군이나 NS 군에 비해서 유의미하게 나타났으며 (p < 0.05), TP 군과는 유의미한 차이를 보이지는 않았다. 2. 제3차원 (3D) 재구성된 이미지 평가 3D 재구성된 이미지에서 피질골 결손 부위를 평가하였다. 모든 방사선 조사 군에서 협측골의 결손된 상태에 비하여 설측골의 결손된 상태가 심하게 나타났다. PTX+TP 군의 결손부 상태는 PTX, TP, NS 군에 비하여 양호하였다. 발치와에서 피질골 결손부와 해면골 결손부 사이의 상관관계를 평가하기 위해 3D 이미지를 사용하였다. 방사선 비조사군에서 골치유가 일어났으며, 발치와는 새롭게 형성된 해면골로 채워지고, 건전한 피질골 벽으로 둘러 쌓여 있는 소견을 보여주었다. 방사선 조사군에서 치유되지 않은 발치와와 골괴사가 관찰되었다. 그리고 잔존한 피질골과 해면골의 부피가 불충분함을 보여주었다. 3. 조직 학적 및 면역 조직 화학적 분석 방사선 조사군에서 골세포가 없는 골소강이 관찰되었는데, 특히 NS 군에서 그러하였다. PTX + TP군에서 하버스관 (haversian canal)에서 살아있는 혈관이 관찰되었으며 PTX 군에서도 적은 양으로 관찰되었다. TP와 NS군에서는 하버스관에서 실활된 혈관이 우세하였다. CD31 (PECAM) 염색을 사용하여 미세 혈관 밀도 (microvessel density, MVD)를 분석하였다. PTX + TP군에서 MVD는 PTX, TP, NS 군에 비하여 MVD가 유의미하게 높게 나타났다 (p < 0.05). osteocalcin (OC) 염색은 피질골 내의 골세포를 평가하기 위해 사용하였다. NS 군에서 OC+ 골세포의 수가 다른 실험군에 비하여 유의미하게 낮게 나타났다 (p < 0.05). PTX +TP, PTX, TP군 간에서는 유의미한 차이를 나타내지는 않았다. TNF-α와 TGF-β1의 발현은 PTX+TP군에서 상대적으로 낮게 나타났다. IL-6, ALP와 같은 다른 마커들에서는 유의미한 차이를 나타내지 않았다. 결론 결과적으로, 피질골은 ORN의 임상적 평가 및 예후에 있어 중요한 역할을 하는 것으로 나타났다. 부가적으로, PTX와 TP는 병용하여 사용하였을 때 강력한 섬유화 억제 작용이 있어 ORN의 치료에 긍정적인 효과를 가지고 있으며, 질환 진행을 후퇴시킬 수 있다. 악골에서 micro-CT는 피질골 분석에서 신뢰 가능한 도구이며, 다른 골구조물 지표의 정량 분석을 강화하는 데 도움을 줄 것이다.Introduction The use of radiotherapy (RT) in head and neck malignancies treatment includes primary therapy, RT as adjuvant to surgery and RT in combination with chemotherapy or as palliative treatment for late stage and unresectable tumors. With recent advances in radiation technique, the undesired effects of irradiation were minimized. However, patients still suffer from reactions of the mucosa, jaw bone or salivary glands, of which one specific adverse effect is osteoradionecrosis (ORN) of the mandible. Pentoxifylline and tocopherol together work as potent antifibrotic agents, which are believed to have the effect of reducing the chronic fibrosis and induce bone healing in ORN. This combination may provide an adjuvant to surgical treatment or an alternative noninvasive treatment for ORN. The study was designed to assess the improvement of cortical bone quality and quantity on irradiated animal model treated with pentoxifylline and tocopherol using a novel micro-CT paradigm. Materials and methods Forty-eight 8-week-old male Sprague-Dawley rats (OrientBio Inc., Seongnam, Korea) with an average body weight of 369.6g were used in this study. Rats were randomly divided into irradiated group (n = 40) and non-irradiated control group (n = 8). In irradiated group, animals were divided into 4 subgroups according to treatment, including PTX + TP (pentoxifylline and tocopherol), PTX (pentoxifylline), TP (tocopherol), and NS (normal saline). Medicine was administrated until the end of the study. Three weeks after irradiation, mandibular posterior teeth were extracted. Animals were sacrificed 7 weeks after irradiation and 4 weeks after extraction. Cortical bone quality and quantity were analyzed using micro-CT and histological evaluation. Alveolar bone height (ABH) and cortical bone thickness (CBT) were compared between non-irradiation control group (C) and irradiated, normal saline administrated group (NS). ABH and CBT were also compared between irradiated groups with different medicine administrated. Cortical bone defect was evaluated on 3D reconstructed images. Results 1. Micro-CT analyses Both ABH and CBT results in group NS were significantly lower than those in non-irradiation group. The ABH and CBT of PTX + TP administrated group were significantly higher than other groups. The ABH and CBT of PTX and TP groups did not differed significantly. The CBT of PTX group was significantly higher than normal saline group (p < 0.05). In all irradiated groups, alveolar bone loss in the lingual side (ΔHL) results were significantly higher than alveolar bone loss in the buccal side (ΔHB). In addition, on buccal side, ΔHB of PTX + TP group was significantly lower compare to PTX group and NS group. On the lingual side, ΔHL of NS group was significantly higher than ΔHL of PTX and PTX + TP group (p < 0.05). In the irradiated group, cortical bone volume (Ct.BV) and total cortical bone surface (Ct.S) of PTX + TP group was significantly higher than which of PTX, TP and NS groups. Average cortical bone thickness (Ct.Th) of PTX + TP group was significantly higher than NS group. The total pore volume (PoV) of 4 groups did not differ significantly. However, total pore volume rate (PoV%) in PTX + TP group was significantly lower than which in PTX and NS groups, and did not significantly differ to TP group (p < 0.05). 2. Three-dimensional (3D) reconstructed images evaluation In all four irradiated groups, observed defective state of lingual walls were more severe than defective state of buccal walls. Also, defective state of PTX + TP group was lower than PTX, TP and NS groups. The 3D reconstructed images were also used to evaluate the correlation between cortical bone defect and cancellous bone defect at the extracted sites. In non-irradiated group, bone healing occurred and the extracted socket was filled with new formed cancellous bone, surrounding by healthy cortical bone walls. In irradiated groups, the non-healing wound and bone necrosis were observed. In addition, there was an inadequacy in the residual volume of cortical bone and cancellous bone. 3. Histological and immunohistochemical analyses We observed empty lacunae with loss of nuclei in irradiated groups, especially in NS group. Viable blood vessels within Haversian canals can be observed in PTX + TP group, and a small amount in PTX group. In TP and NS group, the unviable blood vessels within Haversian canals were dominated. CD31 (PECAM) staining was used for evaluation of microvessel density (MVD). MVD of PTX + TP group was significantly higher than which of PTX, PT and normal saline groups (p < 0.05). Osteocalcin (OC) staining was used for evaluation of osteocyte within cortical bone. Number of OC+ osteocyte in NS group was significantly lower than other three groups. Number of OC+ osteocytes in PTX + TP, PTX and TP groups did not differ significantly (p < 0.05). The expression of TNF-α and TGF-β1 was relatively lower in group taking PTX +TP. The other markers including IL-6, ALP did not show significant difference. Conclusion From the results our study, cortical bone has proven to play an important role in the evaluation and prognosis of ORN. The combination of PTX and TP has improving effect on the cortical bone quality and quantity, resulting in a regression of the disease and can be a reliable treatment protocol or used for early ORN prevention in particular susceptible patients.I. Introduction 01 II. Materials and Methods 04 1. Animal 04 2. Radiation procedures 04 3. Medication, extraction and sacrifice procedures 05 4. Micro-CT scanning and data reconstruction procedures 05 5. Micro-CT analyses 06 6. Histological and immunohistochemical evaluation 07 7. Statistical analysis 08 III. Results 09 1. Alveolar bone height (ABH) and cortical bone thickness (CBT) evaluation 09 2. Cortical bone parameter analyses 09 3 Three-dimensional (3D) reconstructed images evaluation 10 4. Histological and immunohistochemical evaluation 10 IV. Discussion 12 V. Conclusion 18 References 19 Tables 23 Figure legends and Figures 27 Appendix 43 Abstract in Korean 50Maste

International Women Graduate Students: Transition to Public Research Universities in the Midwest

This phenomenological qualitative study explored the experiences of international women graduate students (IWGSs) in transitioning to public research universities in the Midwest. The study utilized Schlossberg’s transition theory (Anderson et al., 2012) to gain insights into the perceptions of six participants during their college transition process. Based on the analysis of data collected through in-depth phenomenological interviews with each participant, three themes emerged that described the challenges faced by the participants during their transition. These themes were: solitary voyage, a dilemma of self-reliance and reliance, and a vicious cycle of limited time and financial constraints. Through the three themes, the study addressed these research questions: How do international women graduate students describe their transition experiences at public research institutions in the Midwest? What student support services do these students believe they need from the university, other networks, and beyond to have a successful transition? Implications for practice and recommendations for student affairs professionals and future research were also provided to better support IWGSs at institutions of higher education in the United States. Advisor: Corey Ruman

Max-Plus線形表現に基づくクリティカルチェイン複数プロジェクト管理手法

国立大学法人長岡技術科学大

On a simple cyclic plasticity modeling with implicit kinematic hardening restoration

10 pagesInternational audienceThis paper presents a fully three-dimensional plastic constitutive modeling framework suitable for the prediction of cyclic loading at large number of cycles. It can require only one yield surface and is motivated by a simple rheological model where a restoration of the kinematic hardening is introduced. The classical kinematic hardening rules are then simply adapted leading to time-dependent evolution laws that are consistent with continuum thermodynamics requirements. The resulting behavior is physically motivated by many man-made materials of engineering interest such as bituminous material. This framework allows all types of yield functions to be easily implemented numerically. This is first illustrated with algorithmic details through a simple associative pressure-insensitive model example of the von Mises type. Then a more elaborated model is given where the present framework is applied to the description of bituminous materials submitted to triaxial static creep and to large number of cyclic loadings. Of particular interest is the ratcheting and the mean stress relaxation. The responses agree well with some experimental test results found in the literature

Denial-of-Service Vulnerability of Hash-based Transaction Sharding: Attacks and Countermeasures

Since 2016, sharding has become an auspicious solution to tackle the scalability issue in legacy blockchain systems. Despite its potential to strongly boost the blockchain throughput, sharding comes with its own security issues. To ease the process of deciding which shard to place transactions, existing sharding protocols use a hash-based transaction sharding in which the hash value of a transaction determines its output shard. Unfortunately, we show that this mechanism opens up a loophole that could be exploited to conduct a single-shard flooding attack, a type of Denial-of-Service (DoS) attack, to overwhelm a single shard that ends up reducing the performance of the system as a whole. To counter the single-shard flooding attack, we propose a countermeasure that essentially eliminates the loophole by rejecting the use of hash-based transaction sharding. The countermeasure leverages the Trusted Execution Environment (TEE) to let blockchain's validators securely execute a transaction sharding algorithm with a negligible overhead. We provide a formal specification for the countermeasure and analyze its security properties in the Universal Composability (UC) framework. Finally, a proof-of-concept is developed to demonstrate the feasibility and practicality of our solution