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- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Decuyper, J., et al.
(author)
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A nonlinear model of vortex-induced forces on an oscillating cylinder in a fluid flow
- 2020
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In: Journal of Fluids and Structures. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0889-9746 .- 1095-8622. ; 96
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Journal article (peer-reviewed)abstract
- A nonlinear model relating the imposed motion of a circular cylinder, submerged in a fluid flow, to the transverse force coefficient is presented. The nonlinear fluid system, featuring vortex shedding patterns, limit cycle oscillations and synchronisation, is studied both for swept sine and multisine excitation. A nonparametric nonlinear distortion analysis (FAST) is used to distinguish odd from even nonlinear behaviour. The information which is obtained from the nonlinear analysis is explicitly used in constructing a nonlinear model of the polynomial nonlinear state-space (PNLSS) type. The latter results in a reduction of the number of parameters and an increased accuracy compared to the generic modelling approach where typically no such information of the nonlinearity is used. The obtained model is able to accurately simulate time series of the transverse force coefficient over a wide range of the frequency-amplitude plane of imposed cylinder motion. (C) 2020 Elsevier Ltd. All rights reserved.
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- Gils, C., et al.
(author)
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Anyonic quantum spin chains : Spin-1 generalizations and topological stability
- 2013
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In: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 87:23, s. 235120-
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Journal article (peer-reviewed)abstract
- There are many interesting parallels between systems of interacting non-Abelian anyons and quantum magnetism occurring in ordinary SU(2) quantum magnets. Here we consider theories of so-called SU(2)(k) anyons, well-known deformations of SU(2), in which only the first k + 1 angular momenta of SU(2) occur. In this paper, we discuss in particular anyonic generalizations of ordinary SU(2) spin chains with an emphasis on anyonic spin S = 1 chains. We find that the overall phase diagrams for these anyonic spin-1 chains closely mirror the phase diagram of the ordinary bilinear-biquadratic spin-1 chain including anyonic generalizations of the Haldane phase, the AKLT construction, and supersymmetric quantum critical points. A novel feature of the anyonic spin-1 chains is an additional topological symmetry that protects the gapless phases. Distinctions further arise in the form of an even/odd effect in the deformation parameter k when considering su(2)(k) anyonic theories with k >= 5, as well as for the special case of the su(2)(4) theory for which the spin-1 representation plays a special role. We also address anyonic generalizations of spin-1/2 chains with a focus on the topological protection provided for their gapless ground states. Finally, we put our results into the context of earlier generalizations of SU(2) quantum spin chains, in particular so-called (fused) Temperley-Lieb chains.
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- Sanchez, Erlan, et al.
(author)
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Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative
- 2024
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In: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
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