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2. Aesthetic gene and prospect of garden city from the perspective of Chinese dream

Author

Liu Mengxuan, Chen Siquan, and An Xu

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

This study aims to delve into the impact of the Chinese Dream ideology on the development and aesthetic characteristics of park cities. Building upon their dialectical and unified relationship, it seeks to predict the evolutionary trajectory of urban modernization and methods to enhance residents' quality of life. Focusing on domestic cases of park city construction, the research employs innovative approaches such as on-site investigations, semi-structured interviews, and literature reviews. A distinctive contribution of this study is the introduction of the concept of "aesthetic genes," which is used to describe and interpret aesthetic elements and cultural features within park cities from five different perspectives. Furthermore, the research offers profound analyses from four distinct viewpoints regarding the future prospects of park city development in the new era. By organically integrating the Chinese Dream ideology with the concept of park cities, this study provides valuable theoretical insights and practical guidance in the fields of sustainable park city construction and urban aesthetics research.

Published
2024
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3. The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma

Author

Pan, Min, Wright, William C., Chapple, Richard H., Zubair, Asif, Sandhu, Manbir, Batchelder, Jake E., Huddle, Brandt C., Low, Jonathan, Blankenship, Kaley B., Wang, Yingzhe, Gordon, Brittney, Archer, Payton, Brady, Samuel W., Natarajan, Sivaraman, Posgai, Matthew J., Schuetz, John, Miller, Darcie, Kalathur, Ravi, Chen, Siquan, Connelly, Jon Patrick, Babu, M. Madan, Dyer, Michael A., Pruett-Miller, Shondra M., Freeman, III, Burgess B., Chen, Taosheng, Godley, Lucy A., Blanchard, Scott C., Stewart, Elizabeth, Easton, John, and Geeleher, Paul

Published
2021
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5. Supplementary Figure S6 from Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis

Author

Kenny, Hilary A., primary, Lal-Nag, Madhu, primary, Shen, Min, primary, Kara, Betul, primary, Nahotko, Dominik A., primary, Wroblewski, Kristen, primary, Fazal, Sarah, primary, Chen, Siquan, primary, Chiang, Chun-Yi, primary, Chen, Yen-Ju, primary, Brimacombe, Kyle R., primary, Marugan, Juan, primary, Ferrer, Marc, primary, and Lengyel, Ernst, primary

Published
2023
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6. Data from Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis

Author

Kenny, Hilary A., primary, Lal-Nag, Madhu, primary, Shen, Min, primary, Kara, Betul, primary, Nahotko, Dominik A., primary, Wroblewski, Kristen, primary, Fazal, Sarah, primary, Chen, Siquan, primary, Chiang, Chun-Yi, primary, Chen, Yen-Ju, primary, Brimacombe, Kyle R., primary, Marugan, Juan, primary, Ferrer, Marc, primary, and Lengyel, Ernst, primary

Published
2023
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7. Supplementary Table S1 from Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis

Author

Kenny, Hilary A., primary, Lal-Nag, Madhu, primary, Shen, Min, primary, Kara, Betul, primary, Nahotko, Dominik A., primary, Wroblewski, Kristen, primary, Fazal, Sarah, primary, Chen, Siquan, primary, Chiang, Chun-Yi, primary, Chen, Yen-Ju, primary, Brimacombe, Kyle R., primary, Marugan, Juan, primary, Ferrer, Marc, primary, and Lengyel, Ernst, primary

Published
2023
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8. Supplementary Methods from Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis

Author

Kenny, Hilary A., primary, Lal-Nag, Madhu, primary, Shen, Min, primary, Kara, Betul, primary, Nahotko, Dominik A., primary, Wroblewski, Kristen, primary, Fazal, Sarah, primary, Chen, Siquan, primary, Chiang, Chun-Yi, primary, Chen, Yen-Ju, primary, Brimacombe, Kyle R., primary, Marugan, Juan, primary, Ferrer, Marc, primary, and Lengyel, Ernst, primary

Published
2023
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9. Data from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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10. Supplementary Figures 1-4 from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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11. Supplementary Figure 8 from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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12. Supplementary Methods, Figure and Table Legends from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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13. Supplementary Table 3A-F from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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14. Supplementary Figures 5-7 from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., primary, Peters, Theodore, primary, Liu, Xiaozhen J., primary, Rappoli, David M., primary, Pickard, Michael D., primary, Menon, Saurabh, primary, Yu, Jie, primary, Driscoll, Denise L., primary, Lingaraj, Trupti, primary, Burkhardt, Anne L., primary, Chen, Wei, primary, Garcia, Khristofer, primary, Sappal, Darshan S., primary, Gray, Jesse, primary, Hales, Paul, primary, Leroy, Patrick J., primary, Ringeling, John, primary, Rabino, Claudia, primary, Spelman, James J., primary, Morgenstern, Jay P., primary, and Lightcap, Eric S., primary

Published
2023
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15. Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs

Author

Kim, Jeremiah Y., primary, Rosenberger, Matthew G., additional, Chen, Siquan, additional, IP, Carman KM, additional, Bahmani, Azadeh, additional, Chen, Qing, additional, Shen, Jinjing, additional, Tang, Yifeng, additional, Wang, Andrew, additional, Kenna, Emma, additional, Son, Minjun, additional, Tay, Savaş, additional, Ferguson, Andrew L., additional, and Esser-Kahn, Aaron P., additional

Published
2023
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19. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

Author

Drayman, Nir, primary, DeMarco, Jennifer K., additional, Jones, Krysten A., additional, Azizi, Saara-Anne, additional, Froggatt, Heather M., additional, Tan, Kemin, additional, Maltseva, Natalia Ivanovna, additional, Chen, Siquan, additional, Nicolaescu, Vlad, additional, Dvorkin, Steve, additional, Furlong, Kevin, additional, Kathayat, Rahul S., additional, Firpo, Mason R., additional, Mastrodomenico, Vincent, additional, Bruce, Emily A., additional, Schmidt, Madaline M., additional, Jedrzejczak, Robert, additional, Muñoz-Alía, Miguel Á., additional, Schuster, Brooke, additional, Nair, Vishnu, additional, Han, Kyu-yeon, additional, O’Brien, Amornrat, additional, Tomatsidou, Anastasia, additional, Meyer, Bjoern, additional, Vignuzzi, Marco, additional, Missiakas, Dominique, additional, Botten, Jason W., additional, Brooke, Christopher B., additional, Lee, Hyun, additional, Baker, Susan C., additional, Mounce, Bryan C., additional, Heaton, Nicholas S., additional, Severson, William E., additional, Palmer, Kenneth E., additional, Dickinson, Bryan C., additional, Joachimiak, Andrzej, additional, Randall, Glenn, additional, and Tay, Savaş, additional

Published
2021
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20. The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma

Author

Pan, Min, primary, Wright, William C., additional, Chapple, Rich, additional, Zubair, Asif, additional, Sandhu, Manbir, additional, Batchelder, Jake, additional, Low, Jonathan, additional, Blankenship, Kaley B, additional, Wang, Yingzhe, additional, Gordon, Brittney, additional, Archer, Payton, additional, Brady, Samuel W., additional, Natarajan, Sivaraman, additional, Posgai, Matthew J., additional, Schuetz, John, additional, Miller, Darcie, additional, Kalathur, Ravi, additional, Chen, Siquan, additional, Connelly, Jon Patrick, additional, Madan Babu, M., additional, Dyer, Michael A., additional, Pruett-Miller, Shondra M., additional, Freeman, Burgess B., additional, Chen, Taosheng, additional, Godley, Lucy A., additional, Blanchard, Scott, additional, Stewart, Elizabeth, additional, Easton, John, additional, and Geeleher, Paul, additional

Published
2021
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21. Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro

Author

Drayman, Nir, primary, Jones, Krysten A., additional, Azizi, Saara-Anne, additional, Froggatt, Heather M., additional, Tan, Kemin, additional, Maltseva, Natalia Ivanovna, additional, Chen, Siquan, additional, Nicolaescu, Vlad, additional, Dvorkin, Steve, additional, Furlong, Kevin, additional, Kathayat, Rahul S., additional, Firpo, Mason R., additional, Mastrodomenico, Vincent, additional, Bruce, Emily A., additional, Schmidt, Madaline M., additional, Jedrzejczak, Robert, additional, Muñoz-Alía, Miguel Á., additional, Schuster, Brooke, additional, Nair, Vishnu, additional, Botten, Jason W., additional, Brooke, Christopher B., additional, Baker, Susan C., additional, Mounce, Bryan C., additional, Heaton, Nicholas S., additional, Dickinson, Bryan C., additional, Jaochimiak, Andrzej, additional, Randall, Glenn, additional, and Tay, Savaş, additional

Published
2020
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22. The gypsy insulator of Drosophila affects chromatin structure in a directional manner

Author

Chen, Siquan and Corces, Victor G.

Subjects
Drosophila -- Genetic aspects, Chromatin -- Research, Biological sciences
Abstract

Chromatin insulators are thought to regulate gene expression by establishing higher-order domains of chromatin organization, although the specific mechanisms by which these sequences affect enhancer-promoter interactions are not well understood. Here we show that the gypsy insulator of Drosophila can affect chromatin structure. The insulator itself contains several DNase I hypersensitive sites whose occurrence is dependent on the binding of the Suppressor of Hairy-wing [Su(Hw)] protein. The presence of the insulator in the 5' region of the yellow gene increases the accessibility of the DNA to nucleases in the promoter-proximal, but not the promoter-distal, region. This increase in accessibility is not due to alterations in the primary chromatin fiber, because the number and position of the nucleosomes appears to be the same in the presence or absence of the insulator. Binding of the Su(Hw) protein to insulator DNA is not sufficient to induce changes in chromatin accessibility, and two domains of this protein, presumed to be involved in interactions with other insulator components, are essential for this effect. The presence of Modifier of mdg4 [Mod(mdg4)] protein, a second component of the gypsy insulator, is required to induce these alterations in chromatin accessibility. The results suggest that the gypsy insulator affects chromatin structure and offer insights into the mechanisms by which insulators affect enhancer-promoter interactions.

Published
2001

23. Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis

Author

Kenny, Hilary A., primary, Lal-Nag, Madhu, additional, Shen, Min, additional, Kara, Betul, additional, Nahotko, Dominik A., additional, Wroblewski, Kristen, additional, Fazal, Sarah, additional, Chen, Siquan, additional, Chiang, Chun-Yi, additional, Chen, Yen-Ju, additional, Brimacombe, Kyle R., additional, Marugan, Juan, additional, Ferrer, Marc, additional, and Lengyel, Ernst, additional

Published
2020
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24. Abstract NT-097: QUANTITATIVE HIGH-THROUGHPUT SCREENING USING AN ORGANOTYPIC MODEL IDENTIFIES TWO KINASE INHIBITORS THAT INHIBIT OVARIAN CANCER METASTASIS

Author

Kenny, Hilary A., primary, Lal, Madhu, additional, Shen, Min, additional, Nahotko, Dominik, additional, Fazal, Sarah, additional, Chen, Siquan, additional, Chiang, Chun-Yi, additional, Kara, Betul, additional, Yamada, S. Diane, additional, Brimacombe, Kyle, additional, Marugan, Juan, additional, Ferrer, Marc, additional, and Lengyel, Ernst, additional

Published
2019
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25. 6mer seed toxicity in viral microRNAs

Author

Murmann, Andrea E., primary, Bartom, Elizabeth T., additional, Schipma, Matthew J., additional, Vilker, Jacob, additional, Chen, Siquan, additional, and Peter, Marcus E., additional

Published
2019
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32. Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.

Author

Murmann, Andrea E., Gao, Quan Q., Putzbach, William E., Patel, Monal, Bartom, Elizabeth T., Law, Calvin Y., Bridgeman, Bryan, Chen, Siquan, McMahon, Kaylin M., Thaxton, C. Shad, and Peter, Marcus E.

Abstract

Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/ CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Effect of substituting elements on thermal stability and glass-forming ability of an Al-based Al[sbnd]Ni[sbnd]Er metallic glass.

Author

Zhang, Wei, Chen, Siquan, Zhu, Zhengwang, Wang, Hao, Li, Yanhui, Kato, Hidemi, and Zhang, Haifeng

Subjects
*METALLIC glasses, *THERMAL stability, *ALUMINUM alloys, *SUPERCOOLED liquids, *THICKNESS measurement
Abstract

Addition of a small amount of La and Co enhances the stabilization of supercooled liquid and glass-forming ability (GFA) of an Al 85 Ni 7 Er 8 metallic glass. The Al 85 Ni 5 Co 2 Er 6 La 2 alloy exhibits large supercooled liquid region of 40 K, high GFA with a critical thickness of 450 μm, and the viscosities on the order of 10 7 −10 9 Pa s in the supercooled liquid state. The Al-based glassy nano-scale patterns were formed by imprinting, indicating its good thermoplastic formability. The possible mechanism for the improvement of the supercooled liquid stability of the Al Ni Er alloy by addition of La and Co elements was discussed in terms of the crystallization behavior. [ABSTRACT FROM AUTHOR]

Published
2017
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34. Lymphoblastoid Cell Lines as a Tool to Study Inter-Individual Differences in the Response to Glucose.

Author

Grassi, Michael A., Rao, Vidhya R., Chen, Siquan, Cao, Dingcai, Gao, Xiaoyu, Cleary, Patricia A., Huang, R. Stephanie, Paterson, Andrew D., Natarajan, Rama, Rehman, Jalees, Kern, Timothy S., and null, null

Subjects
LYMPHOBLASTOID cell lines, INDIVIDUAL differences, DIABETIC retinopathy treatment, GLUCOSE, GENE expression
Abstract

Background: White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy. Methods: Lymphoblastoid cell lines were obtained from twenty-three human subjects. Differences between high and standard glucose conditions were assessed for expression, endothelial adhesion, and reactive oxygen species. Results: Collectively, stimulation of the lymphoblastoid cell lines with high glucose demonstrated corresponding changes on molecular, cellular and functional levels. Lymphoblastoid cell lines up-regulated expression of a panel of genes associated with the leukocyte-mediated inflammation found in diabetic retinopathy that include: a cytokine (IL-1B fold change = 2.11, p-value = 0.02), an enzyme (PKCB fold change = 2.30, p-value = 0.01), transcription factors (NFKB-p50 fold change = 2.05, p-value = 0.01), (NFKB-p65 fold change = 2.82, p-value = 0.003), and an adhesion molecule (CD18 fold change = 2.59, 0.02). Protein expression of CD18 was also increased (p-value = 2.14x10-5). The lymphoblastoid cell lines demonstrated increased adhesiveness to endothelial cells (p = 1.28x10-5). Reactive oxygen species were increased (p = 2.56x10-6). Significant inter-individual variation among the lymphoblastoid cell lines in these responses was evident (F = 18.70, p < 0.0001). Conclusions: Exposure of lymphoblastoid cell lines derived from different human subjects to high glucose demonstrated differential and heterogeneous gene expression, adhesion, and cellular effects that recapitulated features found in the diabetic state. Lymphoblastoid cells may represent a useful tool to guide an individualized understanding of the development and potential treatment of diabetic complications like retinopathy. [ABSTRACT FROM AUTHOR]

Published
2016
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36. Genetic Variation Is the Major Determinant of Individual Differences in Leukocyte Endothelial Adhesion

Author

Grassi, Michael A., primary, Rao, Vidhya, additional, Winkler, Kathryn P., additional, Zhang, Wei, additional, Bogaard, Joseph D., additional, Chen, Siquan, additional, LaCroix, Bonnie, additional, Lenkala, Divya, additional, Rehman, Jalees, additional, Malik, Asrar B., additional, Cox, Nancy J., additional, and Huang, R. Stephanie, additional

Published
2014
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37. Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., additional, Peters, Theodore, additional, Liu, Xiaozhen J., additional, Rappoli, David M., additional, Pickard, Michael D., additional, Menon, Saurabh, additional, Yu, Jie, additional, Driscoll, Denise L., additional, Lingaraj, Trupti, additional, Burkhardt, Anne L., additional, Chen, Wei, additional, Garcia, Khristofer, additional, Sappal, Darshan S., additional, Gray, Jesse, additional, Hales, Paul, additional, Leroy, Patrick J., additional, Ringeling, John, additional, Rabino, Claudia, additional, Spelman, James J., additional, Morgenstern, Jay P., additional, and Lightcap, Eric S., additional

Published
2010
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38. Abstract A70: A genome‐wide siRNA screen for modulators of cell death induced by the proteasome inhibitor bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., additional, Peters, Theodore, additional, Liu, Jane, additional, Rappoli, David M., additional, Pickard, Michael D., additional, Menon, Saurabh, additional, Yu, Jie, additional, Driscoll, Denise L., additional, Lingaraj, Trupti, additional, Burkhardt, Anne L., additional, Chen, Wei, additional, Sappal, Darshan S., additional, Gray, Jesse, additional, Garcia, Khristofer, additional, Hales, Paul, additional, Leroy, Patrick J., additional, Ringeling, John, additional, Rabino, Claudia, additional, Spelman, James J., additional, Morgenstern, Jay P., additional, and Lightcap, Eric S., additional

Published
2009
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39. Influence of different boundary conditions on polarization and phase transition properties of temperature-graded ferroelectric thin films.

Author

Chen Hui, Cheng Taimin, and Chen Siquan

Subjects
BOUNDARY value problems, POLARIZATION (Electricity), PHASE transitions, TEMPERATURE effect, FERROELECTRIC thin films, MAGNETIC coupling
Abstract

In the framework of the mean field approximation, a transverse Ising model is adopted to investigate the influence of two boundary conditions (free boundary condition and clamped boundary condition) on the polarization and phase transition properties of temperature-graded ferroelectric films. Due to the ferroelectric distortion aroused by temperature gradient across the film, the elastic thermal stress in the film increases. A distribution function is introduced to characterize the variation of interaction couplings between two pseudo-spins under different boundary conditions. It's shown that polarization and phase transition temperatures of films under free boundary condition are larger than that of films under clamped boundary condition, and the variation of temperature gradient and film thickness have more obvious influence on films under clamped boundary condition. [ABSTRACT FROM AUTHOR]

Published
2012

40. Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.

Author

Skol AD, Jung SC, Sokovic AM, Chen S, Fazal S, Sosina O, Borkar PP, Lin A, Sverdlov M, Cao D, Swaroop A, Bebu I, Stranger BE, and Grassi MA

Subjects
Adult, Case-Control Studies, Cell Line, Transformed, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 metabolism, Diabetic Retinopathy diagnosis, Diabetic Retinopathy metabolism, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lymphocytes metabolism, Male, Mendelian Randomization Analysis, Proto-Oncogene Proteins metabolism, Quantitative Trait Loci, Tumor Suppressor Proteins metabolism, Young Adult, Diabetes Mellitus, Type 1 genetics, Diabetic Retinopathy genetics, Gene Expression Profiling, Glucose toxicity, Lymphocytes drug effects, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins genetics, Transcriptome, Tumor Suppressor Proteins genetics
Abstract

We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes with and without retinopathy. Those genes exhibiting the largest difference in glucose response were assessed for association with diabetic retinopathy in a genome-wide association study meta-analysis. Expression quantitative trait loci (eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin ( FLCN ) as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy. Independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs with diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy. Integrating genetic association with gene expression implicated FLCN as a disease gene for diabetic retinopathy., Competing Interests: AS, SJ, AS, SC, SF, OS, PB, AL, MS, DC, AS, IB, BS, MG No competing interests declared, (© 2020, Skol et al.)

Published
2020
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41. Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro .

Author

Drayman N, Jones KA, Azizi SA, Froggatt HM, Tan K, Maltseva NI, Chen S, Nicolaescu V, Dvorkin S, Furlong K, Kathayat RS, Firpo MR, Mastrodomenico V, Bruce EA, Schmidt MM, Jedrzejczak R, Muñoz-Alía MÁ, Schuster B, Nair V, Botten JW, Brooke CB, Baker SC, Mounce BC, Heaton NS, Dickinson BC, Jaochimiak A, Randall G, and Tay S

Abstract

There is an urgent need for anti-viral agents that treat SARS-CoV-2 infection. The shortest path to clinical use is repurposing of drugs that have an established safety profile in humans. Here, we first screened a library of 1,900 clinically safe drugs for inhibiting replication of OC43, a human beta-coronavirus that causes the common-cold and is a relative of SARS-CoV-2, and identified 108 effective drugs. We further evaluated the top 26 hits and determined their ability to inhibit SARS-CoV-2, as well as other pathogenic RNA viruses. 20 of the 26 drugs significantly inhibited SARS-CoV-2 replication in human lung cells (A549 epithelial cell line), with EC50 values ranging from 0.1 to 8 micromolar. We investigated the mechanism of action for these and found that masitinib, a drug originally developed as a tyrosine-kinase inhibitor for cancer treatment, strongly inhibited the activity of the SARS-CoV-2 main protease 3CLpro. X-ray crystallography revealed that masitinib directly binds to the active site of 3CLpro, thereby blocking its enzymatic activity. Mastinib also inhibited the related viral protease of picornaviruses and blocked picornaviruses replication. Thus, our results show that masitinib has broad anti-viral activity against two distinct beta-coronaviruses and multiple picornaviruses that cause human disease and is a strong candidate for clinical trials to treat SARS-CoV-2 infection.

Published
2020
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