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7. The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Author

Liu, Chang, Zhou, Daming, Nutalai, Rungtiwa, Duyvesteyn, Helen M.E., Tuekprakhon, Aekkachai, Ginn, Helen M., Dejnirattisai, Wanwisa, Supasa, Piyada, Mentzer, Alexander J., Wang, Beibei, Case, James Brett, Zhao, Yuguang, Skelly, Donal T., Chen, Rita E., Johnson, Sile Ann, Ritter, Thomas G., Mason, Chris, Malik, Tariq, Temperton, Nigel, Paterson, Neil G., Williams, Mark A., Hall, David R., Clare, Daniel K., Howe, Andrew, Goulder, Philip J.R., Fry, Elizabeth E., Diamond, Michael S., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2022
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12. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice

Author

Guo Hanfei, Qian Lei, Chen Xiao, Zhao Yuguang, Song Wei, Guan Yanjie, and Cui Jiuwei

Subjects
immune checkpoint inhibitors, prognostic marker, hyperprogressive disease, Medicine
Abstract

Clinical treatment is challenging for elderly patients with lung cancer who cannot tolerate chemotherapy, do not have cancer driver genes, and have low expression of PD-L1. Since these patients are usually excluded from clinical studies, evidence-based medicine supporting the use of immunotherapy is lacking. Considering the potentially limited clinical benefits and high associated risk of hyperprogressive disease, determining an appropriate treatment is an urgent clinical challenge. We report a 71 year-old male patient diagnosed with advanced lung adenocarcinoma lacking key driving genes (EGFR, ALK, and ROS-1), and low expression of PD-L1 on tumor cells (10–15%). The tumor tissue showed a low level of microsatellite instability, low tumor mutational burden, and no DNA mismatch repair deficiency on whole-exome sequencing (WES). However, a high blood tumor mutational burden was detected. After considering the biomarkers of therapeutic effect and ruling out the risk of hyperprogressive disease, pembrolizumab 200 mg was administered every 3 weeks for a year (17 cycles). The disease remained stable for >39 months, and adverse effects were mild and well-tolerated. Therefore, a comprehensive biomarker evaluation, especially in elderly patients lacking driving genes, is essential. Liquid biopsy technology and WES may be useful for overcoming the limitations of tissue biopsy.

Published
2021
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13. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Author

Liu, Chang, Ginn, Helen M., Dejnirattisai, Wanwisa, Supasa, Piyada, Wang, Beibei, Tuekprakhon, Aekkachai, Nutalai, Rungtiwa, Zhou, Daming, Mentzer, Alexander J., Zhao, Yuguang, Duyvesteyn, Helen M.E., López-Camacho, César, Slon-Campos, Jose, Walter, Thomas S., Skelly, Donal, Johnson, Sile Ann, Ritter, Thomas G., Mason, Chris, Costa Clemens, Sue Ann, Gomes Naveca, Felipe, Nascimento, Valdinete, Nascimento, Fernanda, Fernandes da Costa, Cristiano, Resende, Paola Cristina, Pauvolid-Correa, Alex, Siqueira, Marilda M., Dold, Christina, Temperton, Nigel, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Crook, Derrick, Lambe, Teresa, Clutterbuck, Elizabeth, Bibi, Sagida, Flaxman, Amy, Bittaye, Mustapha, Belij-Rammerstorfer, Sandra, Gilbert, Sarah C., Malik, Tariq, Carroll, Miles W., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Baillie, Vicky, Serafin, Natali, Ditse, Zanele, Da Silva, Kelly, Paterson, Neil G., Williams, Mark A., Hall, David R., Madhi, Shabir, Nunes, Marta C., Goulder, Philip, Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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14. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Author

Graham, Carl, Seow, Jeffrey, Huettner, Isabella, Khan, Hataf, Kouphou, Neophytos, Acors, Sam, Winstone, Helena, Pickering, Suzanne, Galao, Rui Pedro, Dupont, Liane, Lista, Maria Jose, Jimenez-Guardeño, Jose M., Laing, Adam G., Wu, Yin, Joseph, Magdalene, Muir, Luke, van Gils, Marit J., Ng, Weng M., Duyvesteyn, Helen M.E., Zhao, Yuguang, Bowden, Thomas A., Shankar-Hari, Manu, Rosa, Annachiara, Cherepanov, Peter, McCoy, Laura E., Hayday, Adrian C., Neil, Stuart J.D., Malim, Michael H., and Doores, Katie J.

Published
2021
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15. Antibody evasion by the P.1 strain of SARS-CoV-2

Author

Dejnirattisai, Wanwisa, Zhou, Daming, Supasa, Piyada, Liu, Chang, Mentzer, Alexander J., Ginn, Helen M., Zhao, Yuguang, Duyvesteyn, Helen M.E., Tuekprakhon, Aekkachai, Nutalai, Rungtiwa, Wang, Beibei, López-Camacho, César, Slon-Campos, Jose, Walter, Thomas S., Skelly, Donal, Costa Clemens, Sue Ann, Naveca, Felipe Gomes, Nascimento, Valdinete, Nascimento, Fernanda, Fernandes da Costa, Cristiano, Resende, Paola Cristina, Pauvolid-Correa, Alex, Siqueira, Marilda M., Dold, Christina, Levin, Robert, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Crook, Derrick, Lambe, Teresa, Clutterbuck, Elizabeth, Bibi, Sagida, Flaxman, Amy, Bittaye, Mustapha, Belij-Rammerstorfer, Sandra, Gilbert, Sarah C., Carroll, Miles W., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Paterson, Neil G., Williams, Mark A., Hall, David R., Hulswit, Ruben J.G., Bowden, Thomas A., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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16. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Author

Zhou, Daming, Dejnirattisai, Wanwisa, Supasa, Piyada, Liu, Chang, Mentzer, Alexander J., Ginn, Helen M., Zhao, Yuguang, Duyvesteyn, Helen M.E., Tuekprakhon, Aekkachai, Nutalai, Rungtiwa, Wang, Beibei, Paesen, Guido C., Lopez-Camacho, Cesar, Slon-Campos, Jose, Hallis, Bassam, Coombes, Naomi, Bewley, Kevin, Charlton, Sue, Walter, Thomas S., Skelly, Donal, Lumley, Sheila F., Dold, Christina, Levin, Robert, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Crook, Derrick, Lambe, Teresa, Clutterbuck, Elizabeth, Bibi, Sagida, Flaxman, Amy, Bittaye, Mustapha, Belij-Rammerstorfer, Sandra, Gilbert, Sarah, James, William, Carroll, Miles W., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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17. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Author

Supasa, Piyada, Zhou, Daming, Dejnirattisai, Wanwisa, Liu, Chang, Mentzer, Alexander J., Ginn, Helen M., Zhao, Yuguang, Duyvesteyn, Helen M.E., Nutalai, Rungtiwa, Tuekprakhon, Aekkachai, Wang, Beibei, Paesen, Guido C., Slon-Campos, Jose, López-Camacho, César, Hallis, Bassam, Coombes, Naomi, Bewley, Kevin R., Charlton, Sue, Walter, Thomas S., Barnes, Eleanor, Dunachie, Susanna J., Skelly, Donal, Lumley, Sheila F., Baker, Natalie, Shaik, Imam, Humphries, Holly E., Godwin, Kerry, Gent, Nick, Sienkiewicz, Alex, Dold, Christina, Levin, Robert, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Klenerman, Paul, Crook, Derrick, Lambe, Teresa, Clutterbuck, Elizabeth, Bibi, Sagida, Flaxman, Amy, Bittaye, Mustapha, Belij-Rammerstorfer, Sandra, Gilbert, Sarah, Hall, David R., Williams, Mark A., Paterson, Neil G., James, William, Carroll, Miles W., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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18. The antigenic anatomy of SARS-CoV-2 receptor binding domain

Author

Dejnirattisai, Wanwisa, Zhou, Daming, Ginn, Helen M., Duyvesteyn, Helen M.E., Supasa, Piyada, Case, James Brett, Zhao, Yuguang, Walter, Thomas S., Mentzer, Alexander J., Liu, Chang, Wang, Beibei, Paesen, Guido C., Slon-Campos, Jose, López-Camacho, César, Kafai, Natasha M., Bailey, Adam L., Chen, Rita E., Ying, Baoling, Thompson, Craig, Bolton, Jai, Fyfe, Alex, Gupta, Sunetra, Tan, Tiong Kit, Gilbert-Jaramillo, Javier, James, William, Knight, Michael, Carroll, Miles W., Skelly, Donal, Dold, Christina, Peng, Yanchun, Levin, Robert, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Klenerman, Paul, Temperton, Nigel, Hall, David R., Williams, Mark A., Paterson, Neil G., Bertram, Felicity K.R., Siebert, C. Alistair, Clare, Daniel K., Howe, Andrew, Radecke, Julika, Song, Yun, Townsend, Alain R., Huang, Kuan-Ying A., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Diamond, Michael S., Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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19. Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

Author

Huo, Jiandong, Zhao, Yuguang, Ren, Jingshan, Zhou, Daming, Duyvesteyn, Helen M.E., Ginn, Helen M., Carrique, Loic, Malinauskas, Tomas, Ruza, Reinis R., Shah, Pranav N.M., Tan, Tiong Kit, Rijal, Pramila, Coombes, Naomi, Bewley, Kevin R., Tree, Julia A., Radecke, Julika, Paterson, Neil G., Supasa, Piyada, Mongkolsapaya, Juthathip, Screaton, Gavin R., Carroll, Miles, Townsend, Alain, Fry, Elizabeth E., Owens, Raymond J., and Stuart, David I.

Published
2020
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22. Material perception across different media—comparing perceived attributes in oil paintings and engravings

Author

Zhao, Yuguang, Stumpel, Jeroen, de Ridder, Huib, Wijntjes, Maarten W.A., Zhao, Yuguang, Stumpel, Jeroen, de Ridder, Huib, and Wijntjes, Maarten W.A.

Abstract

We investigated the influence of the medium on the perception of depicted objects and materials. Oil paintings and their reproductions in engravings were chosen because they are vastly distinctive media while having completely identical content. A total of 15 pairs were collected, consisting of 88 fragments depicting different materials, including fabric, skin, wood and metal. Besides the original condition, we created three manipulations to understand the effect of colour (a greyscale version) and contrast (equalised histograms towards both painting and engraving). We performed rating experiments on five attributes: three-dimensionality, glossiness, convincingness, smoothness and softness. An average of 25 participants finished each of the 20 online experimental sessions (five attributes X four conditions). Besides clear correlations between the two media, the differences mainly show in their means (different levels of perceived attributes) and standard deviations (perceived range). In most sessions, paintings depict a wider range than engravings. In addition, it was the histogram equalisation (global contrast) that made the most impact on perceived attributes, rather than colour removal. This suggests that engravers compensated for the lack of colour by exploiting the possibilities of local contrast.

Published
2024

23. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Author

Zhou, Daming, Duyvesteyn, Helen M. E., Chen, Cheng-Pin, Huang, Chung-Guei, Chen, Ting-Hua, Shih, Shin-Ru, Lin, Yi-Chun, Cheng, Chien-Yu, Cheng, Shu-Hsing, Huang, Yhu-Chering, Lin, Tzou-Yien, Ma, Che, Huo, Jiandong, Carrique, Loic, Malinauskas, Tomas, Ruza, Reinis R., Shah, Pranav N. M., Tan, Tiong Kit, Rijal, Pramila, Donat, Robert F., Godwin, Kerry, Buttigieg, Karen R., Tree, Julia A., Radecke, Julika, Paterson, Neil G., Supasa, Piyada, Mongkolsapaya, Juthathip, Screaton, Gavin R., Carroll, Miles W., Gilbert-Jaramillo, Javier, Knight, Michael L., James, William, Owens, Raymond J., Naismith, James H., Townsend, Alain R., Fry, Elizabeth E., Zhao, Yuguang, Ren, Jingshan, Stuart, David I., and Huang, Kuan-Ying A.

Published
2020
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24. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Author

Huo, Jiandong, Le Bas, Audrey, Ruza, Reinis R., Duyvesteyn, Helen M. E., Mikolajek, Halina, Malinauskas, Tomas, Tan, Tiong Kit, Rijal, Pramila, Dumoux, Maud, Ward, Philip N., Ren, Jingshan, Zhou, Daming, Harrison, Peter J., Weckener, Miriam, Clare, Daniel K., Vogirala, Vinod K., Radecke, Julika, Moynié, Lucile, Zhao, Yuguang, Gilbert-Jaramillo, Javier, Knight, Michael L., Tree, Julia A., Buttigieg, Karen R., Coombes, Naomi, Elmore, Michael J., Carroll, Miles W., Carrique, Loic, Shah, Pranav N. M., James, William, Townsend, Alain R., Stuart, David I., Owens, Raymond J., and Naismith, James H.

Published
2020
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32. A phase Ib study evaluating the safety and efficacy of IBI310 plus sintilimab in patients with advanced non‐small‐cell lung cancer who have progressed after anti‐PD‐1/L1 therapy.

Author

Zhao, Yuguang, Chen, Xiao, Yao, Jun, Long, Jianlin, Mao, Yong, Wu, Di, Zang, Aimin, Zhao, Jun, Liu, Ziling, Meng, Rui, Chen, Ye, Luo, Yang, Guo, Qun, Li, Li, and Cui, Jiuwei

Subjects
*NON-small-cell lung carcinoma, *IMMUNE checkpoint inhibitors, *ADVERSE health care events, *PROGRESSION-free survival
Abstract

Background: The development of immune checkpoint inhibitors has made a significant breakthrough in the treatment of non‐small‐cell lung cancer (NSCLC). However, there remains a huge unmet clinical need for patients with acquired resistance after initial treatment response. Methods: This study evaluated the combination of IBI310 (an anti‐cytotoxic T lymphocyte‐associated antigen‐4 [CTLA‐4] antibody) and sintilimab (an anti‐programmed death 1 [PD‐1]) antibody) in NSCLC patients who have previously been treated with anti‐PD‐1/ligand (L)1 and acquired resistance. The patients were randomly assigned to receive either a lower dose of IBI310 (1 mg/kg Q3W, cohort A) or a higher dose of IBI310 (3 mg/kg Q3W, cohort B) in combination with sintilimab (200 mg Q3W). The primary endpoints of the study were objective response rate (ORR) assessed by RECISTv1.1 and safety, while secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). Results: As of November 2, 2023, the study had enrolled 30 patients, with 15 patients in each cohort. The ORR was 13.3% (2/15, 95% confidence interval [CI], 1.7–40.5) in cohort B. DCR were 46.7% (95% CI, 21.3–73.4) and 66.7% (95% CI, 38.4–88.2) in cohorts A and B, respectively. In cohorts A and B of this trial, the median follow‐up times were 4.2 and 5.6 months, respectively. Median PFS was 1.45 (95% CI, 1.35–2.73) versus 2.73 (95% CI, 1.41–4.90) months for cohort A versus B; the median OS was 7.03 (95% CI, 3.09–not calculable [NC]) months in cohort A and 8.90 (95% CI, 5.13–NC) months in cohort B. Of the 30 patients, 86.7% in both cohorts experienced treatment‐related adverse events (TRAEs) with Grade ≥3 TRAEs occurring in 40% and 53.3% of patients in cohorts A and B, respectively. Conclusion: IBI310 3 mg/kg Q3W plus sintilimab was effective in a small number of previously treated anti‐PD‐1/L1‐resistant NSCLC patients. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Electrochemistry of aluminium in room temperature A1C13-TMPAC molten salts

Author

Zhao, Yuguang

Subjects
541, Chemistry
Abstract

Aluminium can be electrodeposited on tungsten, aluminium, platinum, nickel and glassy carbon from 2: 1 A1C13-TMPAC (trimethylphenylammonium chloride) molten salts at room temperature. The A1C13-TMPAC melts diluted with 1,2-dichlorobenzene of had a beneficial effect on increasing aluminium deposition and stripping currents by decreasing viscosity and increasing the conductivity of the melt. The reductions of A12C17 ions were quasi-reversible and diffusion controlled, The irreversibility of the reductions was due to the relatively low conductivity and high viscosity of the melts. The aluminium deposition was associated with the reduction of the resulting product A1C14 ions following the locally changing acidity of the melts, and a corrosion reaction between fresh aluminium deposits and the melt. The mechanism for aluminium electrodeposition from 2: 1 A1C13-TMPAC was realised likely similar to that for the acidic A1C13- BPC melts. The bulk depositions of aluminium on all electrode except platinum involved three-dimensional instantaneous nucleation process followed by hemispherical diffusion-controlled growth of the developing nuclei. On platinum the nucleation process was characteristic of instantaneous at short time and then tended to progressive. The phenomena of aluminium UPD were found on all electrodes but not on aluminium itself, highly dependent upon substrates, and involved alloying effects on metal substrates. The UPD layers on the surface of the electrodes corresponded to about 2 -- 10 aluminium monolayer equivalents. The UPD was surface constrained on tungsten, whereas were diffusion controlled on nickel and platinum. The processes on tungsten and platinum were under the limitation of kinetics. On nickel and platinum, the electrodes and the nickel and platinum components in fresh deposits were likely to react with A12C17 and Cl' ions in the melt to form corresponding metal complexes. 11 The passivation phenomena were observed to occur on all electrodes. These could resulted from a black layer formed by AIC13 precipitates. Particularly, on aluminium the stripping of aluminium was involved in an active dissolution-passivation process.

Published
1997

42. Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Author

Huo, Jiandong, Bas, Audrey Le, Ruza, Reinis R., Duyvesteyn, Helen M. E., Mikolajek, Halina, Malinauskas, Tomas, Tan, Tiong Kit, Rijal, Pramila, Dumoux, Maud, Ward, Philip N., Ren, Jingshan, Zhou, Daming, Harrison, Peter J., Weckener, Miriam, Clare, Daniel K., Vogirala, Vinod K., Radecke, Julika, Moynié, Lucile, Zhao, Yuguang, Gilbert-Jaramillo, Javier, Knight, Michael L., Tree, Julia A., Buttigieg, Karen R., Coombes, Naomi, Elmore, Michael J., Carroll, Miles W., Carrique, Loic, Shah, Pranav N. M., James, William, Townsend, Alain R., Stuart, David I., Owens, Raymond J., and Naismith, James H.

Published
2021
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44. Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Author

Huo, Jiangdong, Le Bas, Audrey, Ruza, Reinis R., Duyvesteyn, Helen M. E., Mikolajek, Halina, Malinauskas, Tomas, Tan, Tiong Kit, Rijal, Pramila, Dumoux, Maud, Ward, Philip N., Ren, Jingshan, Zhou, Daming, Harrison, Peter J., Weckener, Miriam, Clare, Daniel K., Vogirala, Vinod K., Radecke, Julika, Moynié, Lucile, Zhao, Yuguang, Gilbert-Jaramillo, Javier, Knight, Michael L., Tree, Julia A., Buttigieg, Karen R., Coombes, Naomi, Elmore, Michael J., Carroll, Miles W., Carrique, Loic, Shah, Pranav N. M., James, William, Townsend, Alain R., Stuart, David I., Owens, Raymond J., and Naismith, James H.

Published
2020
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45. Ferroptosis: Reviewing CRC with the Third Eye

Author

Liu,Xingyu, Tuerxun,Halahati, Li,Yawen, Li,Yaping, He,Yuanyuan, and Zhao,Yuguang

Subjects
Journal of Inflammation Research
Abstract

Xingyu Liu, Halahati Tuerxun, Yawen Li, Yaping Li, Yuanyuan He, Yuguang Zhao Cancer Center, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yuguang Zhao, Cancer Center, the First Hospital of Jilin University, Changchun, People’s Republic of China, Email zhaoyuguang@jlu.edu.cnAbstract: Colorectal cancer (CRC) has been one of the most common cancers and maintains the second-highest incidence and mortality rates among all cancers. The high risk of recurrence and metastasis and poor survival are still huge challenges in CRC therapy, in which the discovery of ferroptosis provides a novel perspective. It has been ten years since a unique type of regulated cell death driven by iron accumulation and lipid peroxidation was proposed and named ferroptosis. During the past decade, there have been multiple pieces of evidence suggesting that ferroptosis participates in the pathophysiological processes during disease progression. In this review, we describe ferroptosis as an imbalance of oxidant systems and anti-oxidants which results in lipid peroxidation, membrane damage, and finally cell death. We elaborate on the mechanisms of ferroptosis and systematically summarize recent studies on the regulatory pathways of ferroptosis in CRC from various perspectives, ranging from encoding genes, noncoding RNAs to regulatory proteins. Finally, we discuss the potential therapeutic role of ferroptosis in CRC treatments.Keywords: ferroptosis, colorectal cancer, redox imbalance, regulatory pathways, therapeutic potential

Published
2022

46. Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy

Author

Jia, Lin, primary, Chen, Naifei, additional, Chen, Xiao, additional, Niu, Chao, additional, Liu, Ziling, additional, Ma, Kewei, additional, Wang, Nanya, additional, Yang, Lei, additional, Zhao, Yuguang, additional, Song, Wei, additional, Lu, Jin, additional, Chen, Chen, additional, Cong, Xiaofeng, additional, Wang, Xu, additional, Xu, Yinghui, additional, Cui, Guozhen, additional, Liu, Zengguang, additional, Chen, Rongrong, additional, Li, Wei, additional, and Cui, Jiuwei, additional

Published
2022
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49. Toremifene interacts with and destabilizes the Ebola virus glycoprotein

Author

Zhao, Yuguang, Ren, Jingshan, Harlos, Karl, Jones, Daniel M., Zeltina, Antra, Bowden, Thomas A., Padilla-Parra, Sergi, Fry, Elizabeth E., and Stuart, David I.

Subjects
Glycoproteins -- Health aspects, Drug interactions -- Observations, Host-virus relationships -- Observations, Ebola virus -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion (1-7). GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered (8-10). Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein-drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14°C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs., The recent outbreak of EBOV in West Africa, the worst of more than 30 in the past 40 years, comprised more than 28,000 cases and over 11,000 deaths (11). In [...]

Published
2016

50. Enhancing Electrocardiogram Identity Recognition Using Convolutional Neural Networks With a Multisimilarity Loss Model

Author

Zhao, Yuguang, Zhao, Lina, Xiao, Zhijun, Li, Jianqing, and Liu, Chengyu

Abstract

Identity recognition plays an important role in human civilization. With people’s further cognition of physiological signals, research on electrocardiogram (ECG)-based identity recognition is gradually carried out at home and abroad. At present, the accuracy of the ECG-based identity recognition is not high, and the generalization ability of the model is weak; to solve this problem, we propose a solution to identity recognition based on multisimilarity loss (MS Loss). First, we filter the signal from ECG identity (ECG-ID) database and feed it into the designed convolutional neural networks (CNNs) for training. After that, the extracted embeddings are then trained with K-nearest neighbor (KNN), support vector machines (SVMs), and Siamese neural networks (Siamese NNs) for recognition. To verify the effectiveness of the embeddings obtained by CNN, we also compared the MS Loss method with the direct training method. To verify the generalization ability of the mode, we collected ECG data from 20 members of the laboratory and established self-built database. Results show that the proposed model has advanced generalization ability than the state-of-the-art works and achieves 97.13% accuracy in the 90-person-scale database and 99.86% recognition accuracy in the 20-person-scale self-built database. This article uses a deep CNN to extract features via MS Loss from ECG signals and realizes quickly distinguishing different individuals, which provides a feasible and natural method for small-scale identification and reduces the difficulty of engineering generalization.

Published
2024
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