Amanda Foks
Universitair hoofddocent
- Naam
- Dr. A.C. Foks
- Telefoon
- +31 71 527 6213
- a.c.foks@lacdr.leidenuniv.nl
- ORCID iD
- 0000-0002-9747-3458
Meer informatie is beschikbaar op de Engelse profielpagina.
Nieuws
Promovendi
Oud Promovendi
Universitair hoofddocent
- Wiskunde en Natuurwetenschappen
- Leiden Academic Centre for Drug Research
- LACDR/Biopharmaceutics
- Schaftenaar F.H., Dam A.D. van, Bruin G. de, Depuydt M.A.C., Mol J., Amersfoort J., Douna H., Meijer M., Kröner M.J., Santbrink P.J. van, Bernabé Kleijn M.N.A., Puijvelde G.H.M. van, Florea B.I., Slütter B., Foks A.C., Bot I., Rensen P.C.N. & Kuiper J. (2024), Immunoproteasomal inhibition with ONX-0914 attenuates atherosclerosis and reduces white adipose tissue mass and metabolic syndrome in mice, Arteriosclerosis, Thrombosis, and Vascular Biology 44(6): 1346–1364.
- Snijckers R.P.M. & Foks A.C. (2024), Adaptive immunity and atherosclerosis: aging at its crossroads, Frontiers in immunology 15: 1350471.
- Smit V., Mol J. de, Bernabé Kleijn M.N.A.B., Depuydt M.A.C., Winther M.P.J. de Bot I., Kuiper J. & Foks A.C. (2024), Sexual dimorphism in atherosclerotic plaques of aged Ldlr-/- mice, Immunity and Ageing 21(1): 27.
- Depuydt M.A.C., Smit V., Schaftenaar F.H., Hemme E., Delfos L., Vlaswinkel F.D., Simpson C., Kovanen P.T., Slütter B.A., Kuiper J., Bot I. & Foks A.C. (2024), Aging promotes mast cell activation and antigen presenting capacity in atherosclerosis, Cardiovascular Research 120(Supplement 1): cvae088.201.
- Bot I., Delfos L., Hemme E., Bernabé Kleijn M.N.A., Santbrink P.J. van, Foks A.C., Kovanen P.T., Jouppila A. & Lassila R. (2024), Treatment with APAC, a dual antiplatelet anticoagulant heparin proteoglycan mimetic, limits early collar-induced carotid atherosclerotic plaque development in Apoe-/- mice, Atherosclerosis 397: 118567.
- Horstmann H., Michel N.A, Sheng X., Hansen S., Lindau A., Pfeil K., Fernandez M.C., Marchini T., Winkels H., Mitre L.S. Abogunloko T., Li X., Mwinyella T. Bon-Nawul, Gissler M.C., Bugger H., Heidt T., Buscher K., Hilgendorf I., Stachon P., Piepenburg S., Verheyen N., Rathner T., Gerhardt T., Siegel P.M., Oswald W.K., Cohnert T., Zernecke A., Madl J., Kohl P., Foks A.C., Muehlen C. von zur, Westermann D., Zirlik A. & Wolf D. (2024), Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis, Cardiovascular Research 120(14): 1713-1726.
- Hemme E., Depuydt M.A.C., Santbrink P.J. van, Wezel A., Smeets H.J., Foks A.C., Kuiper J. & Bot I. (2024), Leukemia inhibitory factor receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr-/- mice, European Journal of Pharmacology 985: 177121.
- Smit V., Mol J. de, Schaftenaar F.H., Depuydt M.A.C., Postel R.J., Smeets D.: Verheijen F.W.M., Bogers L., Duijn J. van, Verwilligen R.A.F., Grievink H.W., Bernabé Kleijn M.N.A., Ingen E. van, Jong M.J.M. de, Goncalves L.: Peeters J.A.H.M., Smeets H.J., Wezel A., Polansky J.K., Winther M.P.J. de, Binder C.J., Tsiantoulas D., Bot I., Kuiper J. & Foks A.C. (2023), Single-cell profiling reveals age-associated immunity in atherosclerosis, Cardiovascular Research 119(15): 2508-2521.
- Delfos L., Depuydt M.A.C., Foks A.C., Bernabe Kleijn M.N.A., Kuiper J., Chemaly M., Peace A., McGilligan V. & Bot I. (2023), NLRP3 inflammasome inhibition by the novel bispecific antibody inflamab inhibits atherosclerosis in apolipoprotein E-deficient mice, Atherosclerosis 379(Supplement 1): S2.
- Depuydt M.A.C., Schaftenaar F.H., Prange H.H.M., Boltjes A., Hemme E., Delfos L., Mol J. de, Jong M.J.M. de, Bernabé Kleijn M.N.A., Peeters J.A.H.M., Goncalves L., Wezel A., Smeets H.J., Borst G.J. de, Foks A.C., Pasterkamp G., Winther M.P.J. de, Kuiper J., Bot I. & Slütter B. (2023), Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells, Nature Cardiovascular Research 2: 112-125.
- Hemme E.: Biskop D., Depuydt M.A.C., Smit V., Delfos L., Bernabé Kleijn M.N.A., Foks A.C., Kuiper J. & Bot I. (2023), Bruton's Tyrosine Kinase inhibition by Acalabrutinib does not affect early or advanced atherosclerotic plaque size and morphology in Ldlr-/- mice, Vascular Pharmacology 150: 107172.
- Douna H., Mol J. de, Amersfoort J., Schaftenaar F.H., Kiss M.G., Suur B.E., Kroner M.J., Binder C.J., Bot I., Puijvelde G.H.M. van, Kuiper J. & Foks A.C. (2022), IFNγ-stimulated B cells inhibit T follicular helper cells and protect against atherosclerosis, Frontiers in Cardiovascular Medicine 9: 781436.
- Mol J. de, Postel R.J., Smit V., Bernabé Kleijn M.N.A., Bot I., Kuiper J. & Foks A.C. (2022), B cell depletion skews cd4+t cell towards a pro-inflammatory phenotype in aged atherosclerotic mice, Cardiovascular Research 118(Supplement_1): cvac066.230.
- Hemme E., Delfos L., Depuydt M.A.C., Bernabé Kleijn M.N.A., Schaftenaar F.H., Foks A.C., Kuiper J. & Bot I. (2022), Brutons tyrosine kinase inhibition to suppress mast cell activation in atherosclerosis, Cardiovascular Research 118(Supplement_1): cvac066.227.
- Depuydt M.A.C., Smit V., Lozano Vigario F., Bernabé Kleijn M.N.A., Vries M.R. de, Quax P.H.A., Wezel A., Smeets H.J., Kuiper J., Foks A.C., Bot I. & Slütter B.A. (2022), Granzyme B+CD4+T cells associate with an unstable plaque phenotype in advanced human atherosclerosis, Cardiovascular Research 118(Supplement_1): cvac066.229.
- Grievink H.W., Smit V., Huisman B.W., Gal P., Yavuz Y., Klerks C., Binder C.J., Bot I., Kuiper J., Foks A.C. & Moerland M. (2022), Cardiovascular risk factors: the effects of ageing and smoking on the immune system, an observational clinical study, Frontiers in immunology 13: 968815.
- Douna H., Smit V., Puijvelde G.H.M. van, Kiss M.G., Binder C.J., Bot I., Kuchroo V.K., Lichtman A.H., Kuiper J. & Foks A.C. (2022), Tim-1 mucin domain-mutant mice display exacerbated atherosclerosis, Atherosclerosis 352: 1-9.
- Liu F., Aulin L.B.S., Kossen S.S.A., Cathalina J.E.J., Bremmer M., Foks A.C., Graaf P.H. van den Moerland M. & Hasselt J.G.C. van (2022), A system pharmacology Boolean network model for the TLR4-mediated inflammatory response in early sepsis, Journal of Pharmacokinetics and Pharmacodynamics 49(6): 645-655.
- Depuydt M.A.C., Vlaswinkel F.D., Hemme E., Delfos L., Bernabe Kleijn M.N.A., Santbrink P.J. van, Foks A.C., Slütter B., Kuiper J. & Bot I. (2022), Blockade of the BLT1-LTB4 axis does not affect mast cell migration towards advanced atherosclerotic lesions in LDLr-/- mice, Scientific Reports 12(1): 18362.
- Postel R.J., Smit V., De Mol J., Bernabé Kleijn M.N.A., De Jong M.J.M., Delfos L., Hemme E., Depuydt M.A.C., Bot I., Kuiper J. & Foks A.C. (2022), IL-21R blockade reduces atherosclerosis development in LDLR-/- mice, Atherosclerosis 355: 23.
- Amersfoort J., Schaftenaar F.H., Douna H., Santbrink P.J. van, Puijvelde G.H.M. van, Slütter B., Foks A.C., Harms A., Moreno-Gordaliza E., Wang Y., Hankemeier T., Bot I., Chi H. & Kuiper J. (2021), Diet-induced dyslipidemia induces metabolic and migratory adaptations in regulatory T cells, Cardiovascular Research 117(5): 1309-1324.
- Duijn J. van, Jong M.J.M. de, Benne N., Leboux R.J.T., Ooijen M.E. van, Kruit N., Foks A.C., Jiskoot W., Bot I., Kuiper J. & Slütter B. (2021), Tc17 CD8+ T-cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development, Cardiovascular Research 117(14): 2755-2766.
- Zhou E., Li Z., Nakashima H., Liu C., Ying Z., Foks A.C., Berbée J.F.P., Dijk K.W. van, Rensen P.C.N. & Wang Y. (2021), Hepatic scavenger receptor class B type 1 knockdown reduces atherosclerosis and enhances the antiatherosclerotic effect of brown fat activation in APOE*3-Leiden.CETP mice, Arteriosclerosis, Thrombosis, and Vascular Biology 41(4): 1474-1486.
- Grievink H.W., Smit V., Verwilligen R.A.F., Bernabé Kleijn M.N.A., Smeets D., Binder C.J., Yagita H., Moerland M., Kuiper J., Bot I. & Foks A.C. (2021), Stimulation of the PD-1 pathway decreases atherosclerotic lesion development in Ldlr deficient mice, Frontiers in Cardiovascular Medicine 8: 740531.
- Ingen E. van, Foks A.C.: Woudenberg T., Bent M.L. van der, Jong A. de, Hohensinner P.J., Wojta J., Bot I., Quax P.H.A. & Nossent A.Y. (2021), Inhibition of microRNA-494-3p activates Wntsignaling and reduces proinflammatorymacrophage polarization in atherosclerosis, Molecular Therapy - Nucleic Acids 26: 1228-1239.
- Mol J. de, Kuiper J., Tsiantoulas D. & Foks A.C. (2021), The dynamics of B cell aging in health and disease, Frontiers in Immunology 12: 733566.
- Douna H., Amersfoort J., Schaftenaar F.H., Kröner M.J., Kiss M.B., Slütter B.A., Depuydt M.A.C., Bernabé Kleijn M.N.A., Wezel A., Smeets H., Yagita H., Binder C.J., Bot I., Puijvelde G.H.M. van, Kuiper J. & Foks A.C. (2020), BTLA stimulation protects against atherosclerosis by regulating follicular B cells, Cardiovascular Research 116(2): 295-305.
- Kritikou E., Depuydt M.A.C., Vries M.R. de, Mulder K.E., Govaert A.M., Smit M.D., Duijn J. van, Foks A.C., Wezel A., Smeets H.J., Slütter B., Quax P.H.A., Kuiper J. & Bot I. (2019), Flow Cytometry-Based Characterization of Mast Cells in Human Atherosclerosis, Cells 8(4): 334.
- Douna H., Amersfoort J., Schaftenaar F.H., Kröner M.J., Kiss M.B., Slütter B., Depuydt M.A.C., Kleijn M.N.A.B., Wezel A., Smeets H., Yagita H., Binder C.J., Bot I., Puijvelde G.H.M. van, Kuiper J. & Foks A.C. (2019), B- and T-lymphocyte attenuator stimulation protects against atherosclerosis by regulating follicular B cells, Cardiovascular Research 116(2): 295-305.
- Douna H., Smit V., Puijvelde G. van, Binder C., Bot I., Kuchroo V., Lichtman A., Kuiper J. & Foks A. (2019), Tim-1 mucin domain-mutant mice display exacerbated atherosclerosis, Atherosclerosis 287: E25-E26.
- Ingen E. van, Foks A.C., Kröner M.J., Kuiper J., Quax P.H.A., Bot I. & Nossent Y. (2019), Inhibition Of Microrna-494 Halts Atherosclerotic Plaque Progression And Stabilizes Advanced Atherosclerotic Lesions, Atherosclerosis 287: E15.
- Ingen E. van, Foks A.C., Kröner M.J., Kuiper J., Quax P.H.A., Bot I. & Nossent A.Y. (2019), Antisense Oligonucleotide Inhibition of MicroRNA-494 Halts Atherosclerotic Plaque Progression and Promotes Plaque Stabilization, Molecular Therapy - Nucleic Acids 18: 638-649.
- Schaftenaar F.H., Amersfoort J., Douna H., Kröner M.J., Foks A.C., Bot I., Slütter B.A., Puijvelde G.H.M. van, Drijfhout J.W. & Kuiper J. (2019), Induction of HLA-A2 restricted CD8 T cell responses against ApoB100 peptides does not affect atherosclerosis in a humanized mouse model, Scientific Reports 9(1): 17391.
- Douna H., Amersfoort J., Schaftenaar F.H., Kroon S., Puijvelde G.H.M. van, Kuiper J. & Foks A.C. (2019), Bidirectional effects of IL-10+ regulatory B cells in Ldlr−/− mice, Atherosclerosis 280: 118-125.
- Foks A.C. (6 februari 2019), Infarct voorkomen met jongere afweercellen. Leidsch Dagblad.
- Puijvelde G.H.M. van, Foks A.C., Bochove R.E. van, Bot I., Habets K.L.L., Jager S.C. de, Borg M.N.D. ter, Osch P. van, Boon L., Vos M., Waard V. de & Kuiper J. (2018), CD1d deficiency inhibits the development of abdominal aortic aneurysms in LDL receptor deficient mice, 13(1): e0190962.
- Duijn J. van, Kritikou E., Benne N., Heijden T. van der, Puijvelde G.H. van, Kröner M.J., Schaftenaar F.H., Foks A.C., Wezel A., Smeets H., Yagita H., Bot I., Jiskoot W., Kuiper J. & Slütter B. (2018), CD8+ T-cells contribute to lesion stabilization in advanced atherosclerosis by limiting macrophage content and CD4+ T-cell responses, Cardiovascular Research 115(4): 729-738.
- Amersfoort J., Douna H., Schaftenaar F.H., Foks A.C., Kröner M.J., Santbrink P.J. van, Puijvelde G.H.M. van, Bot I. & Kuiper J. (2018), Defective Autophagy in T Cells Impairs the Development of Diet-Induced Hepatic Steatosis and Atherosclerosis, Frontiers in Immunology 9: 2937.
- Ingen E. van, Foks A.C., Kröner M.J., Agrawal S., Kuiper J., Quax P.H.A., Bot I. & Nossent A.Y. (2018), Inhibition of microRNA-494 halts atherosclerotic plaque progression and stabilizes advanced atherosclerotic lesions, Cardiovascular Research 114(suppl_1): S57-S57.
- Douna H., Amersfoort J., Schaftenaar F.H., Puijvelde G.H.M. van, Kuiper J. & Foks A.C. (2018), Stimulation of the co-inhibitory BTLA pathway protects against atherosclerosis by selectively reducing atherogenic B cells, Atherosclerosis Supplements 32: 89-89.
- Snip O.S.C., Hoekstra M., Zhao Y., Calpe-Berdiel L., Vulve J., Carles Escola-Gil J., Foks A., Sluis R.J. van der, Blanco-Vaca F., Berkel T.J.C. van, Kuivenhoven J. & Eck M. van (2018), Reduced systemic inflammation and increased reverse cholesterol transport together drive leukocyte ABCA1-mediated protection against atherosclerosis, Atherosclerosis 275: e43-e44.
- Ellenbroek G., Puijvelde G.H.M. van, Anas A.A., Bot M., Asbach M., Schoneveld A., Santbrink P.J. van, Foks A.C., Timmers L., Doevendans P.A., Pasterkamp G., Hoefer I.E., Poll T. van der, Kuiper J. & Jager S.C.A. de (2017), Leukocyte TLR5 deficiency inhibits atherosclerosis by reduced macrophage recruitment and defective T-cell responsiveness, Scientific Reports 7: 42688.
- Heijden T. van der, Kritikou E., Venema W., Duijn J. van, Santbrink P.J. van, Slütter B., Foks A.C., Bot I. & Kuiper J. (2017), NLRP3 Inflammasome Inhibition by MCC950 Reduces Atherosclerotic Lesion Development in Apolipoprotein E-Deficient Mice-Brief Report, Arteriosclerosis, Thrombosis, and Vascular Biology 37(8): 1457-1461.
- Foks A.C. & Kuiper J. (2017), Immune checkpoint proteins: exploring their therapeutic potential to regulate atherosclerosis, British Journal of Pharmacology 174(22): 3940-3955.
- Foks A.C. & Bot I. (2017), Preface: Pathology and Pharmacology of Atherosclerosis, European Journal of Pharmacology 816: 1-2.
- Foks A.C., Puijvelde G.H.M. van, Wolbert J., Kröner M.J., Frodermann V., Heijden T. van der, Santbrink P.J. van, Boon L., Bot I. & Kuiper J. (2016), CD11b+Gr-1+ myeloid-derived suppressor cells reduce atherosclerotic lesion development in LDLr deficient mice, Cardiovascular Research 111(3): 252-261.
- Frodermann V., Duijn J. van, Puijvelde G.H.M. van, Santbrink P.J. van, Lagraauw H.M., Vries M.R. de, Quax P.H.A., Bot I., Foks A.C., Jager S.C. de & Kuiper J. (2016), Heat-killed Staphylococcus aureus reduces atherosclerosis by inducing anti-inflammatory macrophages, Journal of Internal Medicine 279(6): 592-605.
- Louwe M.C., Lammers B., Frias M.A., Foks A.C., Leeuw L.R. de., Hildebrand R.B., Kuiper J., Smit J.W.A., Berkel T.J.C. van, James R.W., Geerling J.J., Rensen P.C.N. & Eck M. van (2016), ABCA1 deficiency protects the heart against myocardial infarction-induced injury, Atherosclerosis 251: 159-163.
- Foks A.C., Engelbertsen D., Kuperwaser F., Alberts-Grill N., Gonen A., Witztum J.L., Lederer J., Jarolim P., DeKruyff R.H., Freeman G.J. & Lichtman A.H. (2016), Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice, Arteriosclerosis, Thrombosis, and Vascular Biology 36(3): 456-465.
- Alberts-Grill N., Engelbertsen D., Bu D., Foks A., Grabie N., Herter J.M., Kuperwaser F., Chen T., Destefano G., Jarolim P. & Lichtman A.H. (2016), Dendritic Cell KLF2 Expression Regulates T Cell Activation and Proatherogenic Immune Responses, Journal of Immunology 197(12): 4651-4662.
- Frodermann V., Puijvelde G.H. van, Wierts L., Lagraauw H.M., Foks A.C., Santbrink P.J. van, Bot I., Kuiper J. & Jager S.C. de (2015), Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis, Journal of Immunology 194(5): 2208-2218.
- Foks A.C., Lichtman A.H. & Kuiper J. (2015), Treating atherosclerosis with regulatory T cells, Arteriosclerosis, Thrombosis, and Vascular Biology 35(2): 280-287.
- Engelbertsen D., Foks A.C., Alberts-Grill N., Kuperwaser F., Chen T., Lederer J.A., Jarolim P., Grabie N. & Lichtman A.H. (2015), Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis, Arteriosclerosis, Thrombosis, and Vascular Biology 35(12): 2526-2535.
- Wezel A., Vries M.R. de, Lagraauw H.M., Foks A.C., Kuiper J., Quax P.H.A. & Bot I. (2014), Complement factor C5a induces atherosclerotic plaque disruptions, Journal of Cellular and Molecular Medicine 18(10): 2020-2030.
- Foks A.C., Ran I.A., Wasserman L., Frodermann V., Borg M.N. ter, Jager S.C. de, Santbrink P.J. van, Yagita H., Akiba H., Bot I., Kuiper J. & Puijvelde G.H.M. van (2013), T-cell immunoglobulin and mucin domain 3 acts as a negative regulator of atherosclerosis, Arteriosclerosis, Thrombosis, and Vascular Biology 33(11): 2558-2565.
- Foks A.C. (6 juni 2013), Regulation of immune responses in atherosclerosis (Dissertatie, Faculty of Science, Leiden University). Promotor(en) en copromotor(en): Kuiper J., Puijvelde G.H.M. van.
- Foks A.C., Puijvelde G.H.M. van, Bot I., Borg M.N. ter, Habets K.L., Johnson J.L., Yagita H., Berkel T.J. van & Kuiper J. (2013), Interruption of the OX40-OX40 ligand pathway in LDL receptor-deficient mice causes regression of atherosclerosis, Journal of Immunology 191(9): 4573-4580.
- Foks A.C., Ran I.A., Frodermann V., Bot I., Santbrink P.J. van, Kuiper J. & Puijvelde G.H.M. van (2013), Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development, PLoS ONE 8(12): e83134.
- Calpe-Berdiel L., Zhao Y., Graauw M. de, Ye D., Santbrink P.J. van, Mommaas A.M., Foks A.C., Bot M., Meurs I., Kuiper J., Mack J.T., Eck M. van, Tew K.D. & Berkel T.J.C. van (2012), Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice, Atherosclerosis 223(2): 332-341.
- Bot I., Vries H. de, Korporaal S.J.A., Foks A.C., Bot M., Veldhoven J.P.D., Borg M.N.D. ter, Santbrink P.J. van, Berkel T.J. van.C., Kuiper J. & Ijzerman A.P. (2012), Adenosine A(2B) Receptor Agonism Inhibits Neointimal Lesion Development After Arterial Injury in Apolipoprotein E-Deficient Mice, Arteriosclerosis, Thrombosis, and Vascular Biology 32(9): 2197-2205.
- Foks A.C., Bot I., Frodermann V., Jager S.C. de, Borg M. ter, Santbrink P.J. van, Yagita H., Kuiper J. & Puijvelde G.H.M. van (2012), Interference of the CD30-CD30L pathway reduces atherosclerosis development, Arteriosclerosis, Thrombosis, and Vascular Biology 32(12): 2862-2868.
- Lammers B., Zhao Y., Foks A.C., Hildebrand R.B., Kuiper J., Berkel T.J. van & Eck M. van (2012), Leukocyte ABCA1 remains atheroprotective in splenectomized LDL receptor knockout mice, PLoS ONE 7(10): e48080.
- Foks A.C., Bot I., Frodermann V., Jager S.C.A. de, Borg M. ter, Santbrink P.J. van, Yagita H., Kuiper J. & Puijvelde G.H.M. van (2012), Interference of the CD30-CD30L pathway reduces atherosclerosis development, Immunology 137: 478-478.
- Foks A.C., Frodermann V., Ter Borg M., Habets K.L., Bot I., Zhao Y., Van Eck M., Van Berkel T.J., Kuiper J. & Van Puijvelde G.H. (2011), Differential effects of regulatory T cells on the initiation and regression of atherosclerosis, Atherosclerosis 218(1): 53-60.
- Es T. van, Puijvelde G.H.M. van, Foks A.C., Habets K.L., Bot I., Gilboa E., Berkel T.J. van & Kuiper J. (2010), Vaccination against Foxp3(+) regulatory T cells aggravates atherosclerosis, Atherosclerosis 209(1): 74-80.
- Wang J., Han W.G., Foks A.C., Huizinga T.W.J. & Toes R.E.M. (2010), Neutralization of IL-4 reverses the nonresponsiveness of CD4+ T cells to regulatory T-cell induction in non-responder mouse strains, Molecular Immunology 48(1-3): 137-146.