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104. Rapid generation of potent antibodies by autonomous hypermutation in yeast

Author

Wellner, Alon, McMahon, Conor, Gilman, Morgan SA, Clements, Jonathan R, Clark, Sarah, Nguyen, Kianna M, Ho, Ming H, Hu, Vincent J, Shin, Jung-Eun, Feldman, Jared, Hauser, Blake M, Caradonna, Timothy M, Wingler, Laura M, Schmidt, Aaron G, Marks, Debora S, Abraham, Jonathan, Kruse, Andrew C, and Liu, Chang C

Subjects
Prevention, Biotechnology, Vaccine Related, Immunization, Generic health relevance, Antibodies, Antibody Formation, Antigens, COVID-19, Humans, Peptide Library, Protein Engineering, Recombinant Proteins, SARS-CoV-2, Saccharomyces cerevisiae, Single-Domain Antibodies, Spike Glycoprotein, Coronavirus, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Biochemistry & Molecular Biology
Abstract

The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, not always accessible and poorly compatible with many antigens. Here, we describe 'autonomous hypermutation yeast surface display' (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. By encoding antibody fragments on an error-prone orthogonal DNA replication system, surface-displayed antibody repertoires continuously mutate through simple cycles of yeast culturing and enrichment for antigen binding to produce high-affinity clones in as little as two weeks. We applied AHEAD to generate potent nanobodies against the SARS-CoV-2 S glycoprotein, a G-protein-coupled receptor and other targets, offering a template for streamlined antibody generation at large.

Published
2021

105. Albuminuria Testing in Hypertension and Diabetes: An Individual-Participant Data Meta-Analysis in a Global Consortium.

Author

Shin, Jung-Im, Chang, Alex, Grams, Morgan, Coresh, Josef, Ballew, Shoshana, Surapaneni, Aditya, Matsushita, Kunihiro, Bilo, Henk, Carrero, Juan, Chodick, Gabriel, Daratha, Kenn, Jassal, Simerjot, Nadkarni, Girish, Nelson, Robert, Nowak, Christoph, Stempniewicz, Nikita, Sumida, Keiichi, Traynor, Jamie, Woodward, Mark, Sang, Yingying, and Gansevoort, Ron

Subjects
albuminuria, blood pressure, diabetes mellitus, hypertension, kidney, prevalence risk, Adult, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Glomerular Filtration Rate, Humans, Hypertension, Middle Aged, Renal Insufficiency, Chronic
Abstract

[Figure: see text].

Published
2021

109. Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis

Author

Shin Jung, Chang Yoon, Kim Tae, Kim Hyung, Ahn Chul, and Byun Min

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background This study was aimed to investigate the diagnostic value of fiberoptic bronchoscopy (FOB) with chest high-resolution computed tomography (HRCT) for the rapid diagnosis of active pulmonary tuberculosis (PTB) in patients suspected of PTB but found to have a negative sputum acid-fast bacilli (AFB) smear. Methods We evaluated the diagnostic accuracy of results from FOB and HRCT in 126 patients at Gangnam Severance Hospital (Seoul, Korea) who were suspected of having PTB. Results Of 126 patients who had negative sputum AFB smears but were suspected of having PTB, 54 patients were confirmed as having active PTB. Hemoptysis was negatively correlated with active PTB. Tree-in-bud appearance on HRCT was significantly associated with active PTB. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FOB alone was 75.9%, 97.2%, 95.3%, and 84.3%, respectively, for the rapid diagnosis of active PTB. The combination of FOB and HRCT improved the sensitivity to 96.3% and the NPV to 96.2%. Conclusions FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB.

Published
2012
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110. Institutional Autonomy and Capacity of Higher Education Governance in South Asia: A Comparative Perspective

Author

Shin, Jung Cheol, Li, Xin, Nam, Inhye, and Byun, Bo-Kyung

Abstract

Recent studies reveal that developing countries cannot achieve good governance in higher education by merely borrowing structures from advanced systems because the globally advocated "one-best-way" approach often ignores levels of institutional capacity in developing countries. This study suggests institutional capacity as a core dimension for practicing good governance in four South Asian countries (Bangladesh, India, Nepal, and Sri Lanka). Building on this, this study compiles data from each country's legislation and the UNESCO data to evaluate the autonomy and capacity of higher education institutions and compares those with Southeast and Northeast Asian countries as a reference. This study finds that these four South Asian countries are grouped into different environments based on the divergent paths to governance improvement suggested for each group. This study concludes that university autonomy is critical for good governance in the long run, whereas it is the capacity building that should be given priority to provide an optimal governance environment.

Published
2022
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111. LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells

Author

Shin Jung-Young, Kim Jeong-Oh, Lee Suk, Chae Hiun-Suk, and Kang Jin-Hyoung

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background As EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A) in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY), a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719. Methods After single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT. Results When 5-FU was sequentially combined with LY, the combination index (CI) value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NFκB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NFκB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (%) increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone. Conclusion These data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance of 5-FU via downregulation of activated p-AKT and mitochondria-dependent apoptosis in EBV gastric cancer cell line, SNU-719.

Published
2010
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114. Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis

Author

Hahn, Jong Woo, Lee, Kwanjoo, Shin, Jae Il, Cho, Seong Ho, Turner, Stephen, Shin, Jung U, Yeniova, Abdullah Özgür, Koyanagi, Ai, Jacob, Louis, Smith, Lee, Fond, Guillaume, Boyer, Laurent, Lee, Seung Won, Kwon, Rosie, Kim, Soeun, Shin, Youn Ho, Rhee, Sang Youl, Moon, Jin Soo, Ko, Jae Sung, Yon, Dong Keon, and Papadopoulos, Nikolaos G.

Published
2023
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115. Protein design and variant prediction using autoregressive generative models.

Author

Shin, Jung-Eun, Riesselman, Adam J, Kollasch, Aaron W, McMahon, Conor, Simon, Elana, Sander, Chris, Manglik, Aashish, Kruse, Andrew C, and Marks, Debora S

Subjects
Humans, Proteins, Antibodies, Antigens, Protein Engineering, Computational Biology, Amino Acid Sequence, Genotype, Phenotype, Mutation, Algorithms, Neural Networks, Computer, Neural Networks, Computer
Abstract

The ability to design functional sequences and predict effects of variation is central to protein engineering and biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments are not robust. Such applications include the prediction of variant effects of indels, disordered proteins, and the design of proteins such as antibodies due to the highly variable complementarity determining regions. We introduce a deep generative model adapted from natural language processing for prediction and design of diverse functional sequences without the need for alignments. The model performs state-of-art prediction of missense and indel effects and we successfully design and test a diverse 105-nanobody library that shows better expression than a 1000-fold larger synthetic library. Our results demonstrate the power of the alignment-free autoregressive model in generalizing to regions of sequence space traditionally considered beyond the reach of prediction and design.

Published
2021

121. Estimated prevalence and trends in smoking among adolescents in South Korea, 2005–2021: a nationwide serial study

Author

Shin, Hyoin, Park, Sangil, Yon, Hyunju, Ban, Chae Yeon, Turner, Stephen, Cho, Seong Ho, Shin, Youn Ho, Shin, Jung U., Koyanagi, Ai, Jacob, Louis, Smith, Lee, Min, Chanyang, Lee, Young Joo, Kim, So Young, Lee, Jinseok, Kwon, Rosie, Koo, Min Ji, Fond, Guillaume, Boyer, Laurent, Hahn, Jong Woo, Kim, Namwoo, Rhee, Sang Youl, Shin, Jae Il, Woo, Ho Geol, Park, Hyeowon, Kim, Hyeon Jin, Lee, Yoonsung, Kim, Man S., Lefkir, Eléa, Hadalin, Vlasta, Choi, Jungwoo, Lee, Seung Won, Yon, Dong Keon, and Kim, Sunyoung

Published
2023
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124. A preliminary study about the potential risks of the UV-weathered microplastic: The proteome-level changes in the brain in response to polystyrene derived weathered microplastics

Author

Kim, Hee-Yeon, Ashim, Janbolat, Park, Song, Kim, Wansoo, Ji, Sangho, Lee, Seoung-Woo, Jung, Yi-Rang, Jeong, Sang Won, Lee, Se-Guen, Kim, Hyun-Chul, Lee, Young-Jae, Kwon, Mi Kyung, Hwang, Jun-Seong, Shin, Jung Min, Lee, Sung-Jun, Yu, Wookyung, Park, Jin-Kyu, and Choi, Seong-Kyoon

Published
2023
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126. Accurate single-shot measurement technique for the spectral distribution of GeV electron beams from a laser wakefield accelerator

Author

Hojbota, Calin Ioan, Kim, Hyung Taek, Shin, Jung Hun, Aniculaesei, Constantin, Rao, Bobbili Sanyasi, and Nam, Chang Hee

Subjects
Physics - Plasma Physics, Physics - Accelerator Physics, Physics - Instrumentation and Detectors
Abstract

We present a technique, based on a dipole magnet spectrometer containing multiple scintillation screens, to accurately characterize the spectral distribution of a GeV electron beam generated by laser wakefield acceleration (LWFA). An optimization algorithm along with a numerical code was developed for trajectory tracing and reconstructing the electron beam angle, divergence, and energy spectrum with a single-shot measurement. The code was validated by comparing the results with the Monte-Carlo simulation of electron beam trajectories. We applied the method to analyze data obtained from laser wakefield acceleration experiments performed using a multi-Petawatt laser to accelerate electron beams to multi-GeV energy. Our technique offers improved accuracy to faithfully characterize electron beams with non-negligible shot-to-shot beam pointing fluctuations, particularly in the state-of-the-art multi-GeV LWFA experiments performed to push the energy frontier., Comment: The following article has been submitted to Review of Scientific Instruments. After it is published, it will be found at https://publishing.aip.org/resources/librarians/products/journals/

Published
2019

139. Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis

Author

Choi, Won-Mook, Yip, Terry Cheuk-Fung, Wong, Grace Lai-Hung, Kim, W. Ray, Yee, Leland J., Brooks-Rooney, Craig, Curteis, Tristan, Cant, Harriet, Chen, Chien-Hung, Chen, Chi-Yi, Huang, Yi-Hsiang, Jin, Young-Joo, Jun, Dae Won, Kim, Jin-Wook, Park, Neung Hwa, Peng, Cheng-Yuan, Shin, Hyun Phil, Shin, Jung Woo, Yang, Yao-Hsu, and Lim, Young-Suk

Published
2023
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141. (Re)turn of the abject : representation of Asian (American) masculinity in the West

Author

Shin, Jung Ju

Subjects
BF Psychology, E11 America (General), HT Communities. Classes. Races, P Philology. Linguistics
Abstract

This thesis examines the Western representation of Asian masculinity in Anglophone literary and popular cultural texts, to discuss how and why these texts illustrate the ways in which the existing hegemonic racial and gender norms maintain and reinforce privilege. The concept of masculinity offers a coherent framework for the investigation of the nature of hegemony. Based on the theoretical frames of hegemonic masculinity and (racial) abjection, the thesis aims to offer an extended understanding of the ideological reconstruction of hegemonic relations between the East and the West and of the changing position of East Asia within contemporary Western as well as global imagination. The system of global neoliberal capitalism still assumes the hegemony of white masculinity and more importantly, works to maintain and reinforce it. I argue that as national/global abject, Asian (American) masculinity reflects relations of power and that behind the celebrated return of the abject to the centre, white hegemonic masculinity still directs the fate of the abject and eventually returns it to its own place of exile, causing the second(ary) abjection that is more difficult to recognise and challenge than before. Through investigation of topics such as racial and gender in/visibility, legacy and lineage, hybridity, the thesis highlights the continuing influence and legacy of white hegemonic masculinity in the allegedly post-racial, post-gender society we live in. The thesis also locates conflicting impulses of reinforcement of and intervention to hegemonic racial and gender ideals within the representations. It examines how hegemony operates within the texts to shape representations of masculinities to the advantage of white hegemonic masculinity, while they also harbour desires to explore possibilities of challenging and disavowing previous forms of hegemony, and asks how we can register progressive changes to the current uneven dynamics of racial and gender hegemony moving away from the repetitive cycle of abjection.

Published
2020

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