The University of Queensland

Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages

Wu, Kai-Chen, Condon, Nicholas D., Hill, Timothy A., Reid, Robert C., Fairlie, David and Lim, Junxian (2023). Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages. Journal of Innate Immunity, 15 (1), 468-484. doi: 10.1159/000530012

PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR

Jiang, Yuhong, Lim, Junxian, Wu, Kai‐Chen, Xu, Weijun, Suen, Jacky Y. and Fairlie, David P. (2021). PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR. British Journal of Pharmacology, 178 (4) bph.15332, 913-932. doi: 10.1111/bph.15332

Europium-labeled synthetic C3a protein as a novel fluorescent probe for human complement C3a receptor

Dantas de Araujo, Aline, Wu, Chongyang, Wu, Kai-Chen, Reid, Robert C., Durek, Thomas, Lim, Junxian and Fairlie, David P. (2017). Europium-labeled synthetic C3a protein as a novel fluorescent probe for human complement C3a receptor. Bioconjugate Chemistry, 28 (6), 1669-1676. doi: 10.1021/acs.bioconjchem.7b00132

Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Lim, Junxian and Fairlie, David P. (2014). Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides. Journal of the American Chemical Society, 136 (34), 11914-11917. doi: 10.1021/ja506518t

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Hamidon, Johan K., Reed, Anthony N., Chu, Peifei, Suen, Jacky Y., Stoermer, Martin J., Blakeney, Jade S., Lim, Junxian, Faber, Jonathan M. and David P. Fairlie, (2013). Downsizing a human inflammatory protein to a small molecule with equal potency and functionality. Nature Communications, 4 (2802) 2802, 1-9. doi: 10.1038/ncomms3802

Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism

Lim, Junxian, Iyer, Abishek, Liu, Ligong, Suen, Jacky Y., Lohman, Rink-Jan, Seow, Vernon, Yau, Mei-Kwan, Brown, Lindsay and Fairlie, David P. (2013). Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism. The FASEB Journal, 27 (12), 4757-4767. doi: 10.1096/fj.13-232702

Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells

Shah, Himani, Hill, Timothy A., Lim, Junxian and Fairlie, David P. (2023). Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells. Journal of Cell Communication and Signaling, 17 (4), 1-15. doi: 10.1007/s12079-023-00791-6

Venom composition and bioactive RF-amide peptide toxins of the saddleback caterpillar, Acharia stimulea (Lepidoptera: Limacodidae)

Goudarzi, Mohaddeseh H., Eagles, David A., Lim, Junxian, Biggs, Kimberley A., Kotze, Andrew C., Ruffell, Angela P., Fairlie, David P., King, Glenn F. and Walker, Andrew A. (2023). Venom composition and bioactive RF-amide peptide toxins of the saddleback caterpillar, Acharia stimulea (Lepidoptera: Limacodidae). Biochemical Pharmacology, 213 115598, 1-11. doi: 10.1016/j.bcp.2023.115598

Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages

Wu, Kai-Chen, Condon, Nicholas D., Hill, Timothy A., Reid, Robert C., Fairlie, David and Lim, Junxian (2023). Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages. Journal of Innate Immunity, 15 (1), 468-484. doi: 10.1159/000530012

Helical structure in cyclic peptides: effect of N-methyl amides versus esters

Wu, Chongyang, Hoang, Huy N., Hill, Timothy A., Lim, Junxian, Kok, W. Mei, Akondi, Kalyani, Liu, Ligong and Fairlie, David P. (2022). Helical structure in cyclic peptides: effect of N-methyl amides versus esters. Chemical Communications, 58 (89), 12475-12478. doi: 10.1039/d2cc05092g

Modifying a hydroxyl patch in glucagon-like peptide 1 produces biased agonists with unique signaling profiles

Wang, Peiqi, Hill, Timothy A., Mitchell, Justin, Fitzsimmons, Rebecca L., Xu, Weijun, Loh, Zhixuan, Suen, Jacky Y., Lim, Junxian, Iyer, Abishek and Fairlie, David P. (2022). Modifying a hydroxyl patch in glucagon-like peptide 1 produces biased agonists with unique signaling profiles. Journal of Medicinal Chemistry, 65 (17), 11759-11775. doi: 10.1021/acs.jmedchem.2c00653

Tuning electrostatic and hydrophobic surfaces of aromatic rings to enhance membrane association and cell uptake of peptides

de Araujo, Aline Dantes, Hoang, Huy N., Lim, Junxian, Mak, Jeffrey and Fairlie, David P. (2022). Tuning electrostatic and hydrophobic surfaces of aromatic rings to enhance membrane association and cell uptake of peptides. Angewandte Chemie International Edition, 61 (29) e202203995, e202203995. doi: 10.1002/anie.202203995

Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake

de Araujo, Aline D., Lim, Junxian, Wu, Kai-Chen, Hoang, Huy N., Nguyen, Huy T. and Fairlie, David P. (2022). Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake. RSC Chemical Biology, 3 (7), 895-904. doi: 10.1039/d1cb00231g

Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides

de Araujo, Aline D., Hoang, Huy N., Lim, Junxian, Mak, Jeffrey Y. W. and Fairlie, David P. (2022). Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides. Angewandte Chemie, 134 (29). doi: 10.1002/ange.202203995

Temporal perturbation of histone deacetylase activity reveals a requirement for HDAC1–3 in mesendoderm cell differentiation

Sinniah, Enakshi, Wu, Zhixuan, Shen, Sophie, Naval-Sanchez, Marina, Chen, Xiaoli, Lim, Junxian, Helfer, Abbigail, Iyer, Abishek, Tng, Jiahui, Lucke, Andrew J., Reid, Robert C., Redd, Meredith A., Nefzger, Christian M., Fairlie, David P. and Palpant, Nathan J. (2022). Temporal perturbation of histone deacetylase activity reveals a requirement for HDAC1–3 in mesendoderm cell differentiation. Cell Reports, 39 (7) 110818, 1-21. doi: 10.1016/j.celrep.2022.110818

The histone deacetylase Hdac7 supports LPS‐inducible glycolysis and Il‐1β production in murine macrophages via distinct mechanisms

Ramnath, Divya, Das Gupta, Kaustav, Wang, Yizhuo, Abrol, Rishika, Curson, James E. B., Lim, Junxian, Reid, Robert C., Mansell, Ashley, Blumenthal, Antje, Karunakaran, Denuja, Fairlie, David P. and Sweet, Matthew J. (2022). The histone deacetylase Hdac7 supports LPS‐inducible glycolysis and Il‐1β production in murine macrophages via distinct mechanisms. Journal of Leukocyte Biology, 111 (2), 327-336. doi: 10.1002/jlb.2mr1021-260r

HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates

Mak, Jeffrey Y. W., Wu, Kai-Chen, Gupta, Praveer K., Barbero, Sheila, McLaughlin, Maddison G., Lucke, Andrew J., Tng, Jiahui, Lim, Junxian, Loh, Zhixuan, Sweet, Matthew J, Reid, Robert C., Liu, Ligong and Fairlie, David P. (2021). HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates. Journal of Medicinal Chemistry, 64 (4), 2186-2204. doi: 10.1021/acs.jmedchem.0c01967

PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR

Jiang, Yuhong, Lim, Junxian, Wu, Kai‐Chen, Xu, Weijun, Suen, Jacky Y. and Fairlie, David P. (2021). PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR. British Journal of Pharmacology, 178 (4) bph.15332, 913-932. doi: 10.1111/bph.15332

Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition

Kennedy, Amanda J., Sundström, Linda, Geschwindner, Stefan, Poon, Eunice K. Y., Jiang, Yuhong, Chen, Rongfeng, Cooke, Rob, Johnstone, Shawn, Madin, Andrew, Lim, Junxian, Liu, Qingqi, Lohman, Rink-Jan, Nordqvist, Anneli, Fridén-Saxin, Maria, Yang, Wenzhen, Brown, Dean G., Fairlie, David P. and Dekker, Niek (2020). Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition. Communications Biology, 3 (1) 782, 782. doi: 10.1038/s42003-020-01504-0

Achiral derivatives of hydroxamate AR-42 potently inhibit class I HDAC enzymes and cancer cell proliferation

Tng, Jiahui, Lim, Junxian, Wu, Kai-Chen, Lucke, Andrew J., Xu, Weijun, Reid, Robert C. and Fairlie, David P. (2020). Achiral derivatives of hydroxamate AR-42 potently inhibit class I HDAC enzymes and cancer cell proliferation. Journal of Medicinal Chemistry, 63 (11) acs.jmedchem.0c00230, 5956-5971. doi: 10.1021/acs.jmedchem.0c00230

Potent thiophene antagonists of human complement C3a receptor with anti-inflammatory activity

Rowley, Jessica A., Reid, Robert C., Poon, Eunice K. Y., Wu, Kai-Chen, Lim, Junxian, Lohman, Rink-Jan, Hamidon, Johan K., Yau, Mei-Kwan, Halili, Maria A., Durek, Thomas, Iyer, Abishek and Fairlie, David P. (2020). Potent thiophene antagonists of human complement C3a receptor with anti-inflammatory activity. Journal of Medicinal Chemistry, 63 (2) acs.jmedchem.9b00927, 529-541. doi: 10.1021/acs.jmedchem.9b00927

Bicyclic helical peptides as dual inhibitors selective for Bcl2A1 and Mcl-1 proteins

de Araujo, Aline D., Lim, Junxian, Wu, Kai-Chen, Xiang, Yibin, Good, Andrew C., Skerlj, Renato and Fairlie, David P. (2018). Bicyclic helical peptides as dual inhibitors selective for Bcl2A1 and Mcl-1 proteins. Journal of Medicinal Chemistry, 61 (7), 2962-2972. doi: 10.1021/acs.jmedchem.8b00010

A potent antagonist of protease-activated receptor 2 that inhibits multiple signaling functions in human cancer cells

Jiang, Yuhong, Yau, Mei-Kwan, Lim, Junxian, Wu, Kai-Chen, Xu, Weijun, Suen, Jacky Y and Fairlie, David P (2018). A potent antagonist of protease-activated receptor 2 that inhibits multiple signaling functions in human cancer cells. The Journal of pharmacology and experimental therapeutics, 364 (2), 246-257. doi: 10.1124/jpet.117.245027

Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a

Lohman, Rink-Jan, Hamidon, Johan K., Reid, Robert C., Rowley, Jessica A., Yau, Mei-Kwan, Halili, Maria A., Nielsen, Daniel S., Lim, Junxian, Wu, Kai-Chen, Loh, Zhixuan, Do, Anh, Suen, Jacky Y., Iyer, Abishek and Fairlie, David P. (2017). Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a. Nature Communications, 8 (1) 351, 351. doi: 10.1038/s41467-017-00414-w

Europium-labeled synthetic C3a protein as a novel fluorescent probe for human complement C3a receptor

Dantas de Araujo, Aline, Wu, Chongyang, Wu, Kai-Chen, Reid, Robert C., Durek, Thomas, Lim, Junxian and Fairlie, David P. (2017). Europium-labeled synthetic C3a protein as a novel fluorescent probe for human complement C3a receptor. Bioconjugate Chemistry, 28 (6), 1669-1676. doi: 10.1021/acs.bioconjchem.7b00132

Biased signaling by agonists of protease activated receptor 2

Jiang, Yuhong, Yau, Mei-Kwan, Kok, W. Mei, Lim, Junxian, Wu, Kai-Chen, Liu, Ligong, Hill, Timothy A., Suen, Jacky Y. and Fairlie, David P. (2017). Biased signaling by agonists of protease activated receptor 2. ACS Chemical Biology, 12 (5), 1217-1226. doi: 10.1021/acschembio.6b01088

Mapping transmembrane residues of proteinase activated recpetor 2 (PAR2) that influence ligand-modulated calcium signaling

Suen, J.Y., Adams, M. N., Lim, J., Madala, P.K., Xu, W, Cotterell, A., He, Y., Yua, Mei-Kwan, Hooper, J. D. and Fairlie, D.P. (2017). Mapping transmembrane residues of proteinase activated recpetor 2 (PAR2) that influence ligand-modulated calcium signaling. Pharmacological Research, 117, 328-342. doi: 10.1016/j.phrs.2016.12.020

Electrophilic helical peptides that bond covalently, irreversibly, and selectively in a protein-protein interaction site

Dantas De Araujo, Aline, Lim, Junxian, Good, Andrew C., Skerlj, Renato T. and Fairlie, David P. (2017). Electrophilic helical peptides that bond covalently, irreversibly, and selectively in a protein-protein interaction site. ACS Medicinal Chemistry Letters, 8 (1), 22-26. doi: 10.1021/acsmedchemlett.6b00395

Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

Seow, Vernon, Lim, Junxian, Cotterell, Adam J., Yau, Mei-Kwan, Xu, Weijun, Lohman, Rink-Jan, Kok, W. Mei, Stoermer, Martin J., Sweet, Matthew J., Reid, Robert C., Suen, Jacky Y. and Farilie, David P. (2016). Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists. Scientific Reports, 6 (1) 24575, 24575.1-24575.12. doi: 10.1038/srep24575

Protease activated receptor 2 (PAR2) modulators: a patent review (2010–2015)

Yau, Mei-Kwan, Lim, Junxian, Liu, Ligong and Fairlie, David P. (2016). Protease activated receptor 2 (PAR2) modulators: a patent review (2010–2015). Expert Opinion on Therapeutic Patents, 26 (4), 471-483. doi: 10.1517/13543776.2016.1154540

Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity

Yau, Mei-Kwan, Liu, Ligong, Lim, Junxian, Lohman, Rink-Jan, Cotterell, Adam J., Suen, Jacky Y., Vesey, David A., Reid, Robert C. and Fairlie, David P. (2016). Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity. Bioorganic and Medicinal Chemistry Letters, 26 (3), 986-991. doi: 10.1016/j.bmcl.2015.12.048

PAR2 modulators derived from GB88

Yau, Mei-Kwan, Liu, Ligong, Suen, Jacky Y., Lim, Junxian, Lohman, Rink-Jan, Jiang, Yuhong, Cotterell, Adam J., Barry, Grant D., Mak, Jeffrey Y. W., Vesey, David A., Reid, Robert C. and Fairlie, David P. (2016). PAR2 modulators derived from GB88. ACS Medicinal Chemistry Letters, 7 (12), 1179-1184. doi: 10.1021/acsmedchemlett.6b00306

Potent small agonists of protease activated receptor 2

Yau, Mei-Kwan, Suen, Jacky Y., Xu, Weijun, Lim, Junxian, Liu, Ligong, Adams, Mark N., He, Yaowu, Hooper, John D., Reid, Robert C. and Fairlie, David P. (2016). Potent small agonists of protease activated receptor 2. ACS Medicinal Chemistry Letters, 7 (1), 105-110. doi: 10.1021/acsmedchemlett.5b00429

Repurposing Registered Drugs as Antagonists for Protease-Activated Receptor 2

Xu, Weijun, Lim, Junxian, Goh, Chai-Yeen, Suen, Jacky Y., Jiang, Yuhong, Yau, Mei-Kwan, Wu, Kai-Chen, Liu, Ligong and Fairlie, David P. (2015). Repurposing Registered Drugs as Antagonists for Protease-Activated Receptor 2. Journal of Chemical Information and Modeling, 55 (10), 2079-2084. doi: 10.1021/acs.jcim.5b00500

Three homology models for PAR2 derived from different templates: Application to antagonist discovery

Perry, Samuel R., Xu, Weijun, Wirija, Anna, Lim, Junxian, Yau, Mei-Kwan, Stoermer, Martin J., Lucke, Andrew J. and Fairlie, David P. (2015). Three homology models for PAR2 derived from different templates: Application to antagonist discovery. Journal of Chemical Information And Modeling, 55 (6), 1181-1191. doi: 10.1021/acs.jcim.5b00087

Potent heterocyclic ligands for human complement C3a receptor

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Hamidon, Johan K., Lim, Junxian, Stoermer, Martin J. and Fairlie, David P. (2014). Potent heterocyclic ligands for human complement C3a receptor. Journal of Medicinal Chemistry, 57 (20), 8459-8470. doi: 10.1021/jm500956p

Pathway-selective antagonism of proteinase activated receptor 2

Suen, J. Y., Cotterell, A., Lohman, R. J., Lim, J., Han, A., Yau, M. K., Liu, L., Cooper, M. A., Vesey, D. A. and Fairlie, D. P. (2014). Pathway-selective antagonism of proteinase activated receptor 2. British Journal of Pharmacology, 171 (17), 4112-4124. doi: 10.1111/bph.12757

Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Lim, Junxian and Fairlie, David P. (2014). Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides. Journal of the American Chemical Society, 136 (34), 11914-11917. doi: 10.1021/ja506518t

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Hamidon, Johan K., Reed, Anthony N., Chu, Peifei, Suen, Jacky Y., Stoermer, Martin J., Blakeney, Jade S., Lim, Junxian, Faber, Jonathan M. and David P. Fairlie, (2013). Downsizing a human inflammatory protein to a small molecule with equal potency and functionality. Nature Communications, 4 (2802) 2802, 1-9. doi: 10.1038/ncomms3802

Inflammatory Responses Induced by Lipopolysaccharide Are Amplified in Primary Human Monocytes but Suppressed in Macrophages by Complement Protein C5a

Seow, Vernon, Lim, Junxian, Iyer, Abishek, Suen, Jacky Y., Ariffin, Juliana K., Hohenhaus, Daniel M., Sweet, Matthew J. and Fairlie, David P. (2013). Inflammatory Responses Induced by Lipopolysaccharide Are Amplified in Primary Human Monocytes but Suppressed in Macrophages by Complement Protein C5a. Journal of Immunology, 191 (8), 4308-4316. doi: 10.4049/jimmunol.1301355

Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism

Lim, Junxian, Iyer, Abishek, Liu, Ligong, Suen, Jacky Y., Lohman, Rink-Jan, Seow, Vernon, Yau, Mei-Kwan, Brown, Lindsay and Fairlie, David P. (2013). Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism. The FASEB Journal, 27 (12), 4757-4767. doi: 10.1096/fj.13-232702

C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling

Liu, Junxian, Iyer, Abishek, Suen, Jacky Y., Seow, Vernon, Reid, Robert C., Brown, Lindsay and Fairlie, David P. (2013). C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling. The FASEB Journal, 27 (2), 822-831. doi: 10.1096/fj.12-220582

An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats

Iyer, Abishek, Lim, Junxian, Poudyal, Hemant, Reid, Robert C., Suen, Jacky Y., Webster, Julie, Prins, Johannes B., Whitehead, Jonathan P., Fairlie, David P. and Brown, Lindsay (2012). An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats. Diabetes, 61 (9), 2320-2329. doi: 10.2337/db11-1179

Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats

Iyer, Abishek, Fenning, Andrew, Lim, Junxian, Le, Giang T, Reid, Robert C, Halili, Maria A, Fairlie, David P and Brown, Lindsay (2010). Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats. British Journal of Pharmacology, 159 (7), 1408-1417. doi: 10.1111/j.1476-5381.2010.00637.x

Structure-activity relationships for substrate-based inhibitors of human complement factor B

Ruiz-Gomez, G, Lim, J, Halili, M. A., Le, G. T., Madala, P. K., Abbenante, G and Fairlie, D. P. (2009). Structure-activity relationships for substrate-based inhibitors of human complement factor B. JOURNAL OF MEDICINAL CHEMISTRY, 52 (19), 6042-6052. doi: 10.1021/jm900781m

Heterocycles for switching GPCR ligand conformation and activity

Fairlie, David, Reid, Robert, Rowley, Jessica, Wu, Kai-Chen, Yau, Mei-Kwan, Lim, Junxian and Iyer, Abishek (2019). Heterocycles for switching GPCR ligand conformation and activity. National Meeting of the American Chemical Society (ACS), Orlando, FL United States, 31 March-4 April 2019. Washington, DC United States: American Chemical Society.

Potent small agonists of protease activated receptor 2

Yau, Mei Kwan, Suen, Jacky, Xu, Weijun, Lim, Junxian, Liu, Ligong, Adams, Mark, He, Yaowu, Hooper, John, Reid, Robert and Fairlie, David (2015). Potent small agonists of protease activated receptor 2. WASHINGTON: AMER CHEMICAL SOC.

Downsizing Proteins Without Losing Potency or Function

Fairlie, David P. , Yau, Mei-Kwan , Hamidon, Johan K. , Singh, Ranee , Lim, Junxian , Suen, Jacky Y. , Rowley, Jessica A. , Lohman, Rink-Jan , Stoermer, Martin J. , Iyer, Abishek and Reid, Robert C. (2015). Downsizing Proteins Without Losing Potency or Function. American Peptide Symposium 2015, Orlando , Florida, United States, 20-25 June 2015. American Peptide Society. doi: 10.17952/24APS.2015.016