그래프 신경망의 스펙트럴 해석과 그 응용

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 수리과학부, 2023. 8. 강명주.In this dissertation, we present a theoretical analysis of spectral-based graph neural networks and their practical performance. We analyze how the spectra of a graph Laplacian relates to the convolution operation of a graph neural network, and we discuss how expressive a graph convolutional model can be and how competent expressiveness can be achieved by implementing various convolutions on a graph based on this spectra. The results show that spectral-based graph neural networks can perform well on graph-based tasks, and we discuss what improvements can be made in the future to improve their performance in practice. As an extension, we apply it to traditional computer vision tasks in addition to graph-based tasks and show that it is comparably expressive. In addition, we present several results of its applications utilizing graphs. Specifically, we conducted experiments on the task of salient object detection using directed acyclic graphs. We also show experimental results of applying the simple model based on the theory of Fourier analysis to practical applications such as the rain removal task. These experiments empirically demonstrate that incorporating the knowledge of graph theory and Fourier analysis into the model helps improve performance.본 눈문에서는 스펙트럼 기반 그래프 인공신경망의 이론적 분석과 그 실용적 성능에 대해 다룬다. 그래프 신경망에서의 컨볼루션 연산과 라플라시안 그래프의 스펙트럼 간의 관계를 조사하고, 어떤 가정들 하에서 그래프 컨볼루션이 정의될 수 있으며, 그러한 가정 아래에서 어떤 방식으로 그래프 컨볼루션을 정확히 표현할 수 있는 지에 대해 분석하였다. 이러한 분석을 기반으로 다양한 그래프 컨볼루션을 실험하여 모델의 표현력과 성능을 논의하였다. 결과적으로, 스펙트럼 기반 그래프 신경망이 그래프 기반 작업에서 우수한 성능을 보여줌을 확인하며, 실제 성능을 향상시키기 위한 개선 가능한 부분에 대해 논의한다. 더불어, 이론과 적용 영역을 확장하여 그래프 기반 작업뿐만 아니라 전통적인 컴퓨터 비전 작업 등에도 적용할 수 있음을 보여주어 이러한 방식의 확장성을 보여주었다. 마지막으로 이 논문에서는 그래프를 활용한 몇 가지 응용 사례와 결과를 제시하였다. 구체적인 실험으로 방향성 비순환 그래프(DAG)를 이용한 두드러진 물체 검출 작업에 대한 실험을 수행하였다. 이외에도 푸리에 변환을 활용한 모듈을 활용하여 비를 제거하는 태스크 같은 실용적 분야에 적용한 모델과 실험 결과들을 살펴본다. 이러한 실험들을 통해, 그래프 이론과 푸리에 분석 지식과 같은 수학적 지식을 모델에 통합하고 이를 분석하는 것이 성능 향상에 유용함을 실증적으로 보여주었다.Abstract 1 Introduction 1 2 Preliminaries 4 2.1 Graph Neural Networks 4 2.1.1 Mathematical Terminologies 4 2.1.2 Graph Message Passing 5 2.1.3 Spatial-based Graph Neural Networks 6 2.1.4 Spectral-based Graph Neural Networks 8 2.2 Collaborative Filtering 8 2.3 Directed Acyclic Graphs Learning 10 3 Related Works 12 3.1 Spectral-based Graph Neural Networks 12 3.1.1 Spectral Network 12 3.1.2 ChebNet 12 3.1.3 Graph Convolutional Networks 13 3.2 Collaborative Filtering 13 3.3 Salient Object Detection 15 3.4 Rain Removal Tasks 17 4 Spectral Analysis of Graph Neural Networks 20 4.1 Schwartz space S (Rd) and Ring graph Rn 20 4.2 Convolution on General Graphs 25 5 Proposed Method 30 5.1 Proposal Background 30 5.2 Spectral GNNs to Computational Fluid Dynamics 31 5.3 Collaborative Filtering 33 5.4 Salient Object Detection 34 5.5 Rain Removal Task 36 6 Experiments 39 6.1 Spectral GNNs to Computational Fluid Dynamics 39 6.1.1 Datasets 39 6.1.2 Experimental Results 40 6.2 Collaborative Filtering 45 6.2.1 Datasets 45 6.2.2 Evaluation Metric 46 6.2.3 Bayesian Personalized Ranking 47 6.2.4 Experimental Results 49 6.3 Salient Object Detection 50 6.3.1 Datasets 50 6.3.2 Evaluation metrics 51 6.3.3 Experimental Results 52 6.4 Rain Removal Task 57 6.4.1 Datasets 57 6.4.2 Experimental Results 57 7 Conclusion 63 References 65 Abstract (in Korean) 73박

PD-1 Blockade Reinvigorates Bone Marrow CD8 + T Cells from Patients with Multiple Myeloma in the Presence of TGFβ Inhibitors

Purpose: Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma. Experimental design: Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti-PD-1 and TGFβ inhibitors. Results: We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1-expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti-PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti-PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFβ, which was overexpressed by myeloma cells. Conclusions: Our findings indicate that combined blockade of PD-1 and TGFβ may be useful for the treatment of multiple myeloma.ope

Mothers and Fathers in Playing-Teaching Task Situations: Do They Interact and Influence Infants' Language Development Differently?

학위논문 (석사)-- 서울대학교 대학원 : 심리학과 발달심리학 전공, 2016. 2. 곽금주.Infants develop and acquire basic language skills as they interact with their caregivers. As sensitive teachers, friendly playmates, or challenging partners, parents aid infants language development. As active participants, infants, in turn, learn, understand, and express various words and phrases. Therefore, parent-infant interaction is important in early language development in infancy. Most of the previous studies observed mother-infant interaction during free-play situation, and revealed that mothers responsiveness, didactic behaviors, and emotions aid infants language achievement. On the other hand, the study about father-infant interaction has not received attention until recently. Also, researchers have claimed that free-play situation is limited to represent parent-infant interaction as a whole. Therefore, the current study observed mother- and father-infant interaction during free-play and teaching-task situations to examine behavioral differences between mothers and fathers, and analyze unique relationship between mothers and fathers behaviors and infants language comprehension and production. Parent-infant interaction was observed when the infants were at 9 months, and the interactions were coded with Caregiver-Child Affect, Responsiveness, and Engagement Scale (C-CARES). Also, infants language comprehension and production were measured with MacArthur-Bates Communicative Inventory-Korean (M-B CDI-K) when infants were at 9 and 12 months of age. Results indicated that mothers and fathers displayed different behavioral patterns when interacting with their infants. Also, parents behaviors were different across free-play and teaching-task situations. In addition, significant parent x situation, parent x infant gender, and parent x situation x infant gender interaction effects were found. Moreover, different mothers and fathers behavioral variables were associated with infants language measures. Specifically, mothers disciplinary and negative verbalization and fathers teasing and task-oriented behavior continuously predicted infants language comprehension and production. Mothers behaviors can be explained as culture-specific behavioral pattern, and fathers behaviors can be explained as fathers unique contribution. Implications and limitations are further discussed.Introduction 1 Interaction with Mother and Language Development 5 Interaction with Father and Language Development 11 Interaction in Free-play and Teaching-task Situations and Language Development 16 The Current Study 19 Method 23 Participants 23 Procedures 23 Measures 24 Results 29 Differences in Parents Behaviors by Parent Gender, Situation, and Infant Gender 30 Relationship between Parents Behaviors and Infants Language Measures 39 Predictive Relationship between Parents Behaviors and Infants Language Measures 48 Discussion 55 Parents Behaviors: Mother versus Father, Free-play versus Teaching-task Situation and Infant Gender 57 Parents Behaviors and Infants Language Development 61 Mothers and Fathers Unique and Longitudinal Contribution to Language Development 63 Implications and Limitations 66 References 69 국문초록 84Maste

Reversible Pulmonary Hypertension due to Sick Sinus Syndrome

A 60-year-old man visited the hospital after experiencing dyspnea after exertion for 2 weeks. An electrocardiogram showed sinus arrest with junctional escape rhythm at 40 beats/min. Transthoracic echocardiography showed that the right ventricular systolic pressure (RVSP) was approximately 71 mmHg and that the left ventricular ejection fraction was preserved. The ratio of peak early diastolic transmitral inflow velocity to early diastolic peak mitral annular velocity (E/E’) was 29. Cardiac catheterization revealed a systolic pulmonary artery pressure (SPAP) of 63 mmHg, a mean pulmonary artery pressure of 27 mmHg, and a pulmonary capillary wedge pressure of 22 mmHg with a rhythm of 40 beats/min. The patient was diagnosed with pulmonary hypertension (group 2) due to sick sinus syndrome. SPAP decreased to 48 mmHg during atrial pacing at 60 beats/min. After permanent pacemaker insertion, RVSP decreased from 71 mmHg to 44 mmHg. In this case, passive group 2 pulmonary hypertension occurred due to sick sinus syndrome.ope

Visual Question Answering using Simple Natural Language Processing

학위논문 (석사)-- 서울대학교 대학원 : 공과대학 컴퓨터공학부, 2018. 8. 이상구.시각적 질의응답이란 기계학습 분야에 최근 등장한 과제로서, 이미지와 자연언어 질문이 주어졌을 때, 이미지에 있는 정보를 바탕으로 질문에 대한 정확한 답변을 하는 과제를 말한다. 이는 컴퓨터 비전과 자연언어처리(Natural Language Processing)이라는 큰 갈래로 나누어져서 진행이 되던 연구들의 교차로 기로에 있는 중요한 연구 주제이다. 위 과제를 해결하기 위해 최근 다양한 딥러닝 기반의 모델들이 쏟아져 나오고 있다. 이러한 다양한 모델들이 좋은 성능을 보이지만, 장소를 묻는 질문에 예(yes) 라고 대답하고, 비슷하지만 다른 질문에 똑같은 대답 을 하는 등의 자연어 질문에 대한 이해 부족으로 짐작되는 현상들이 두루 나타난다. 따라서 본 연구에서는 위에서 지적한 문제점을 해결하기 위해 문장 분류 와 품사 태깅을 이용하여, 좋은 성능을 유지하면서 기계의 자연어 질문에 대한 이해도를 높이는 새로운 시각적 질의응답 모델을 제안한다. 정확도를 포함한 다양한 실험 결과, 본 연구가 제시하는 자연어 질문에 대한 이해도 를 평가하는 척도에서 다른 모델보다 좋게 나왔으며, 성능 또한 기존의 최 고 성능을 보이는 모델[4]과 비슷한 것을 확인했다.제 1장 서론 . １ 제 2장 관련 연구 ４ 2.1 기본 모델(Baseline Model) . ４ 2.2 어텐션 기반 모델(Attention Based Model) ７ 2.3 Bilinear Pooling 기반 모델 . １０ 제 3장 자연 언어처리를 이용한 시각적 질의응답 １３ 3.1 기존 연구의 한계점 １３ 3.2 문장 분류와 품사 태깅을 이용한 질문 인코딩 １５ 3.2.1 분장 분류를 통한 정답 형태 예측 . １６ 3.2.2 품사 태깅을 이용한 질문 간소화. １９ 3.3 자연언어처리를 활용한 시각적 질의응답 모델 ２２ 제 4장 실험 방법 및 결과 ２８ 4.1 데이터 셋과 실험 방법 . ２８ 4.1.1 학습 데이터 셋 ２８ 4.1.2 평가 기준 . ３０ 4.2 실험 결과 및 분석 ３４ 4.2.1 모델의 내부 실험 결과와 분석 ３４ 4.2.2 기존 모델들과의 비교 . ３７ 제 5장 결론 및 향후 연구 ４５ 5.1 결론 ４５ 5.2 향후 연구 . ４５ 참고 문헌 ４７ Abstract . ５１Maste

Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating Mcl-1 in acute myeloid leukaemia cells

Background: The evasion of apoptosis through dysregulated Bcl-2 family members is a hallmark of leukaemia stem cells (LSCs) in acute myeloid leukaemia (AML). Therefore, targeting Bcl-2 with venetoclax has been suggested as an attractive strategy for inducing apoptosis in AML LSCs. However, the selective inhibition of Bcl-2 in AML often leads to upregulation of Mcl-1, another dominant anti-apoptotic Bcl-2 family protein conferring venetoclax resistance. Methods: We assessed the combined effect of venetoclax and arsenic trioxide (ATO) on leukaemic cell viability, apoptosis, combination index, and cell cycle in the human LSC-like KG1 and KG1a cells. The synergistic effect of venetoclax and ATO on apoptosis was also examined in primary CD34+ and CD34+CD38- LSCs from the bone marrow (BM) of AML patients, and compared with those from healthy donors. Results: Venetoclax efficiently impaired cell viability and dose-dependently promoted apoptosis when combined with ATO; their synergism was aptly represented by the combination index. The combination of venetoclax and ATO impaired cell cycle progression by restricting cells within the sub-G1 phase and facilitating caspase-dependent apoptotic cell death associated with the loss of mitochondrial membrane potential, while sparing healthy BM haematopoietic stem cells. Mechanistically, ATO mitigated venetoclax-induced upregulation of Mcl-1 by the inhibition of AKT and ERK, along with activation of GSK-3β. This led to the Mcl-1 destabilisation, triggering Noxa and Bim to facilitate apoptosis and the consequent activation of the apoptosis executioner protein Bak. Moreover, the combination promoted phosphorylation of ATM, Chk2, p38, and H2AX, indicating an active DNA damage response. Conclusions: Our findings demonstrate the synergistic, preferential antileukaemic effects of venetoclax and ATO on LSCs, providing a rationale for preclinical and clinical trials by combining these agents already being used in clinical practice to treat acute leukaemia.ope

Transvenous pacemaker lead removal in pacemaker lead endocarditis with large vegetations: a report of two cases.

Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics.ope

Deferoxamine Reduces Inflammation and Osteoclastogenesis in Avulsed Teeth

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase-polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague-Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.ope

Incidence of Febrile Neutropenia in Korean Female Breast Cancer Patients Receiving Preoperative or Postoperative Doxorubicin/Cyclophosphamide Followed by Docetaxel Chemotherapy

PURPOSE: Doxorubicin/cyclophosphamide followed by docetaxel chemotherapy (AC-D) is an intermediate risk factor (incidence of 10%-20%) for febrile neutropenia (FN) in breast cancer. However, the reported incidence of FN while using this regimen was obtained mostly from Western breast cancer patients, with little data available from Asian patients. This study aimed to assess the incidence of FN in Korean breast cancer patients and to describe clinical variables related to FN. METHODS: From September 2010 to February 2013, data from the Yonsei Cancer Center registry of breast cancer patients who received neoadjuvant or adjuvant chemotherapy with four cycles of AC-D (60 mg/m(2) doxorubicin, 600 mg/m(2) cyclophosphamide every 3 weeks for four cycles followed by 75 mg/m(2) or 100 mg/m(2) docetaxel every 3 weeks for four cycles) were analyzed. The incidence of FN, FN associated complications, dose reduction/delays, and relative dose intensity (RDI) were investigated. RESULTS: Among the 254 patients reported to the registry, the FN incidence after AC-D chemotherapy was 29.5% (75/254), consisting of 25.2% (64/254) events during AC and 4.7% (12/254) during docetaxel chemotherapy. Dose reductions, delays, and RDI less than 85.0% during AC were observed in 16.5% (42/254), 19.5% (47/254), and 11.0% (28/254) of patients, respectively. Patients with FN events frequently experienced dose reduction/delays, which eventually led to a decreased RDI. CONCLUSION: The incidence of FN during AC-D neoadjuvant or adjuvant chemotherapy was higher than expected in Korean breast cancer patients. Whether these patients should be classified as a high-risk group for FN warrants future prospective studies.ope

DRP1 Inhibition Enhances Venetoclax-Induced Mitochondrial Apoptosis in TP53-Mutated Acute Myeloid Leukemia Cells through BAX/BAK Activation

Although TP53 mutations in acute myeloid leukemia (AML) are associated with poor response to venetoclax, the underlying resistance mechanism remains unclear. Herein, we investigated the functional role of dynamin-related protein 1 (DRP1) in venetoclax sensitivity in AML cells with respect to TP53 mutation status. Effects of DRP1 inhibition on venetoclax-induced cell death were compared in TP53-mutated (THP-1 and Kasumi-1) and TP53 wild-type leukemia cell lines (MOLM-13 and MV4-11), as well as in primary AML cells obtained from patients. Venetoclax induced apoptosis in TP53 wild-type AML cells but had limited effects in TP53-mutated AML cells. DRP1 expression was downregulated in MOLM-13 cells after venetoclax treatment but was unaffected in THP-1 cells. Cotreatment of THP-1 cells with venetoclax and a TP53 activator NSC59984 downregulated DRP1 expression and increased apoptosis. Combination treatment with the DRP1 inhibitor Mdivi-1 and venetoclax significantly increased mitochondria-mediated apoptosis in TP53-mutated AML cells. The combination of Mdivi-1 and venetoclax resulted in noticeable downregulation of MCL-1 and BCL-xL, accompanied by the upregulation of NOXA, PUMA, BAK, and BAX. These findings suggest that DRP1 is functionally associated with venetoclax sensitivity in TP53-mutated AML cells. Targeting DRP1 may represent an effective therapeutic strategy for overcoming venetoclax resistance in TP53-mutated AML.ope