Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies

Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens. In this thesis I determined that the early stages of efferosome maturation parallel that of the pro-immunogenic phagocytosis of pathogens. Mass spectrometry analysis of later maturation stages identified unique regulatory proteins on efferosomes and phagosomes. Keys among these were Rab17 and Rab45 on efferosomes versus Rab6b and PI-4-Kinase on phagosomes. The later would allow for antigen presentation from phagosomes, while the former would direct efferosome-derived antigens away from this presentation pathway. Moreover, positive regulators of MAP-kinase signaling were enriched on phagosomes, while negative regulators were enriched on efferosomes, perhaps indicating the mechanism through which efferocytosis inhibits inflammation. These regulators may account for the differences in inflammation and immunogenicity observed after efferocytosis versus phagocytosis

The effect of environmental factors on accounting systems: a comparison between South Korea and Australia

As globalization of the business environment increases, cross-national accounting differences have been the main focus of international accounting research. Specifically, the relationship between accounting and environmental factors has been the subject of many debates over the last decade. In comparative studies of accounting history, culture and practices, researchers have become increasingly aware of the importance of environmental factors in shaping a country's accounting system. This study explores whether environmental factors influence accounting systems by comparing South Korea and Australia. Although both South Korea and Australia were colonies, they had different cultural backgrounds and different legal/judicial systems. Australia's accounting standards-setting process is based on business practices and is relatively open to public opinion, while Korea's accounting standards tend to be enforced by the government and harmonized to tax law. Many prior studies suggest that environmental factors can be a valuable tool in explaining and understanding differences in the way in which accounting operates in countries with different environments. Based on environmental factors, this study found that cultural factors and institutional structures have a significant influence on the development of accounting systems and cause their differences. This study is expected to provide a systematic framework for differences in the development of accounting systems by analyzing the effects of environmental factors on accounting systems

URANS Computations of Cavitating Flow around a 2-D Wedge by Compressible Two-Phase Flow Solver

This paper deals with the computation of unsteady cavitating flow around a twodimensional wedge by using Unsteady Reynolds Averaged Navier-Stokes (URANS) flow solver. Because of accuracy deterioration problem due to excessive numerical dissipations for low Mach number unsteady flow, properly scaled RoeM and AUSMPW+ numerical flux schemes are used to accurately compute unsteady cavitating flow. Fast Fourier Transform (FFT) analysis results of experiments and computations are compared to show similar dominant frequencies of shedding vortices. Shedding pattern and location of vortices are also compared to show similar behavior of each flow result.OAIID:RECH_ACHV_DSTSH_NO:A201606327RECH_ACHV_FG:RR00200003ADJUST_YN:EMP_ID:A001138CITE_RATE:FILENAME:M2J.1.AS733_1588F1.pdfDEPT_NM:기계항공공학부EMAIL:[email protected]_YN:FILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/d3e93894-8ef1-4bce-9dfe-e2c270ced9d8/linkCONFIRM:

Acoustic Aberration in Non-Invasive Histotripsy Therapy.

Acoustic aberration effects have been extensively studied over the years for high intensity focused ultrasound (HIFU) due to the significant therapeutic disruption they can cause in thermal ablation procedures, often rendering the treatment ineffective without the implementation of aberration correction mechanisms. Histotripsy therapy uses highly energetic cavitation bubble clouds to mechanically fractionate tissue. The cavitation bubble cloud initiation is dependent on a pressure threshold mechanism, which allows this process to be controlled by the pressure amplitude available at the focus. The work presented herein explores the therapeutic effects of acoustic aberration in the scope of histotripsy therapy and investigates the feasibility of conducting non-invasive histotripsy procedures without using correction mechanisms in distinct therapeutic contexts likely to introduce high degrees of acoustic aberration. The first context investigated is transcostal therapy. It is demonstrated that histotripsy therapy is able to generate precise lesions through rib obstacles without aberration correction despite the presence of large grating lobes in the focal profile. An in vivo study follows, in which comparable porcine liver lesions are created through windows with full and no ribcage obstruction, inducing no visible damage on overlying tissues. The second context investigates transabdominal fetal therapy. It is shown that histotripsy therapy can achieve precise fetal tissue ablation in sheep models through the intact maternal abdomen without aberration correction. A long-term study on the impact of the therapy in the course of pregnancy is conducted, indicating the potential safety of this technique for non-invasive fetal applications. The third, and perhaps the most challenging therapeutic context involves transcranial therapy. A large aperture array transducer is specifically designed, and a novel sonication mechanism using extremely short pulses with large negative pressures is introduced. It is shown that precise cavitation lesions can be successfully generated transcranially by careful modulation of the focal pressure amplitude. Overall results show that the pressure threshold mechanism governing the initiation of histotripsy bubble clouds lends the therapy a considerable degree of immunity against acoustic aberration effects, a feature, which in combination with the low thermal impact of the therapy would be highly beneficial for a variety of non-invasive therapeutic applications.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/100071/1/yohankim_1.pd

Discovery of Novel Mechanisms Regulating Cancer Extravasation in the Chorioallantoic Membrane Model

Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and establish the secondary site in the metastatic cascade. Although extravasation encompasses key events during cancer cell invasion to aid in the development of effective treatments, an in vivo model that rapidly, reproducibly and economically recapitulates cancer cell extravasation is needed. Therefore, the objectives of my research were to 1) establish and validate an in vivo model of cancer cell extravasation, and 2) identify novel cellular and molecular events. I used the chorioallantoic membrane of chicken embryos as a model system of extravasation as it provides an accessible and highly vascularized structure. The combination of the chorioallantoic membrane of chicken embryos, nanoscale flow cytometry, and confocal microscopy-based intravital imaging allowed me to observe that extravasating prostate cancer cells exhibited significant cell volume reduction. This reduction is suggestive of an invasive cell phenotype. However, cell volume reduction at certain threshold also decreased cancer cell extravasation efficiency. I also found that cancer cell released extravascular vesicles during extravasation, and an increase in extracellular vesicle release reduced cell volume. I then tested the hypothesis that extracellular vesicle release and extravasation may be linked to modes of cell death. Real-time imaging of extravasating cancer cells that released extracellular vesicles did not show activation of caspase-3. Activation of necroptosis, however, increased extracellular vesicle release and decreased cell extravasation and secondary colony formation. These results suggest that necroptosis may be targeted to induce extracellular vesicle release, decrease extravasation, and halt cancer metastasis. Collectively, my work lays out the protocols for the use of the chorioallantoic membrane of chicken embryos as a model system to investigate cancer cell extravasation and invasion. Use of this model system allowed me to identify extracellular vesicle release during extravasation and discover that necroptosis may be a potential regulator of cancer metastasis

Invisible Computing

The computer is no longer a tool solely used for enhancing the productivity of organizational tasks. Rather, computing capability now is embedded into our everyday artifacts, enabling our daily activities to become smarter and easier. As a result, the way we interact with computers has radically changed in the past few years: computing is now being designed for activity-oriented users. Thus, as IS and HCI scholars have discussed, computing should be designed to be invisible. By invisible we mean the phenomenon that users are not conscious of the computing that they are using. The degree of invisibility largely depends on user interfaces of computing. The concept of invisibility has been used among IS and HCI scholars. However, detailed analysis on invisibility as a construct has not been conducted. Therefore, in this paper, we will investigate 1) where and how the concept of invisibility has been used in the literature, 2) a new theoretical framework for the concept of invisibility in computing, and 3) how this concept can provide practical implications by applying it to a related case. In this paper, we focus on the relation between computing devices and users at the individual level with respect to degrees of invisibility

Implicit Kernel Attention

\textit{Attention} computes the dependency between representations, and it encourages the model to focus on the important selective features. Attention-based models, such as Transformers and graph attention networks (GAT) are widely utilized for sequential data and graph-structured data. This paper suggests a new interpretation and generalized structure of the attention in Transformer and GAT. For the attention in Transformer and GAT, we derive that the attention is a product of two parts: 1) the RBF kernel to measure the similarity of two instances and 2) the exponential of $L^{2}$ norm to compute the importance of individual instances. From this decomposition, we generalize the attention in three ways. First, we propose implicit kernel attention with an implicit kernel function, instead of manual kernel selection. Second, we generalize $L^{2}$ norm as the $L^{p}$ norm. Third, we extend our attention to structured multi-head attention. Our generalized attention shows better performance on classification, translation, and regression tasks

NeBLa: Neural Beer-Lambert for 3D Reconstruction of Oral Structures from Panoramic Radiographs

Panoramic radiography (panoramic X-ray, PX) is a widely used imaging modality for dental examination. However, its applicability is limited as compared to 3D Cone-beam computed tomography (CBCT), because PX only provides 2D flattened images of the oral structure. In this paper, we propose a new framework which estimates 3D oral structure from real-world PX images. Since there are not many matching PX and CBCT data, we used simulated PX from CBCT for training, however, we used real-world panoramic radiographs at the inference time. We propose a new ray-sampling method to make simulated panoramic radiographs inspired by the principle of panoramic radiography along with the rendering function derived from the Beer-Lambert law. Our model consists of three parts: translation module, generation module, and refinement module. The translation module changes the real-world panoramic radiograph to the simulated training image style. The generation module makes the 3D structure from the input image without any prior information such as a dental arch. Our ray-based generation approach makes it possible to reverse the process of generating PX from oral structure in order to reconstruct CBCT data. Lastly, the refinement module enhances the quality of the 3D output. Results show that our approach works better for simulated and real-world images compared to other state-of-the-art methods.Comment: 10 pages, 4 figure

Dataset size and composition impact the reliability of performance benchmarks for peptide-MHC binding predictions

BACKGROUND: It is important to accurately determine the performance of peptide:MHC binding predictions, as this enables users to compare and choose between different prediction methods and provides estimates of the expected error rate. Two common approaches to determine prediction performance are cross-validation, in which all available data are iteratively split into training and testing data, and the use of blind sets generated separately from the data used to construct the predictive method. In the present study, we have compared cross-validated prediction performances generated on our last benchmark dataset from 2009 with prediction performances generated on data subsequently added to the Immune Epitope Database (IEDB) which served as a blind set. RESULTS: We found that cross-validated performances systematically overestimated performance on the blind set. This was found not to be due to the presence of similar peptides in the cross-validation dataset. Rather, we found that small size and low sequence/affinity diversity of either training or blind datasets were associated with large differences in cross-validated vs. blind prediction performances. We use these findings to derive quantitative rules of how large and diverse datasets need to be to provide generalizable performance estimates. CONCLUSION: It has long been known that cross-validated prediction performance estimates often overestimate performance on independently generated blind set data. We here identify and quantify the specific factors contributing to this effect for MHC-I binding predictions. An increasing number of peptides for which MHC binding affinities are measured experimentally have been selected based on binding predictions and thus are less diverse than historic datasets sampling the entire sequence and affinity space, making them more difficult benchmark data sets. This has to be taken into account when comparing performance metrics between different benchmarks, and when deriving error estimates for predictions based on benchmark performance.Fil: Kim, Yohan. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sidney, John. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Buus, Søren. Universidad de Copenhagen; DinamarcaFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unido