144 research outputs found
A Deep Learning approach to Reduced Order Modelling of Parameter Dependent Partial Differential Equations
Within the framework of parameter dependent PDEs, we develop a constructive
approach based on Deep Neural Networks for the efficient approximation of the
parameter-to-solution map. The research is motivated by the limitations and
drawbacks of state-of-the-art algorithms, such as the Reduced Basis method,
when addressing problems that show a slow decay in the Kolmogorov n-width. Our
work is based on the use of deep autoencoders, which we employ for encoding and
decoding a high fidelity approximation of the solution manifold. In order to
fully exploit the approximation capabilities of neural networks, we consider a
nonlinear version of the Kolmogorov n-width over which we base the concept of a
minimal latent dimension. We show that this minimal dimension is intimately
related to the topological properties of the solution manifold, and we provide
some theoretical results with particular emphasis on second order elliptic
PDEs. Finally, we report numerical experiments where we compare the proposed
approach with classical POD-Galerkin reduced order models. In particular, we
consider parametrized advection-diffusion PDEs, and we test the methodology in
the presence of strong transport fields, singular terms and stochastic
coefficients
On the latent dimension of deep autoencoders for reduced order modeling of PDEs parametrized by random fields
Deep Learning is having a remarkable impact on the design of Reduced Order
Models (ROMs) for Partial Differential Equations (PDEs), where it is exploited
as a powerful tool for tackling complex problems for which classical methods
might fail. In this respect, deep autoencoders play a fundamental role, as they
provide an extremely flexible tool for reducing the dimensionality of a given
problem by leveraging on the nonlinear capabilities of neural networks. Indeed,
starting from this paradigm, several successful approaches have already been
developed, which are here referred to as Deep Learning-based ROMs (DL-ROMs).
Nevertheless, when it comes to stochastic problems parameterized by random
fields, the current understanding of DL-ROMs is mostly based on empirical
evidence: in fact, their theoretical analysis is currently limited to the case
of PDEs depending on a finite number of (deterministic) parameters. The purpose
of this work is to extend the existing literature by providing some theoretical
insights about the use of DL-ROMs in the presence of stochasticity generated by
random fields. In particular, we derive explicit error bounds that can guide
domain practitioners when choosing the latent dimension of deep autoencoders.
We evaluate the practical usefulness of our theory by means of numerical
experiments, showing how our analysis can significantly impact the performance
of DL-ROMs
Approximation bounds for convolutional neural networks in operator learning
Recently, deep Convolutional Neural Networks (CNNs) have proven to be
successful when employed in areas such as reduced order modeling of
parametrized PDEs. Despite their accuracy and efficiency, the approaches
available in the literature still lack a rigorous justification on their
mathematical foundations. Motivated by this fact, in this paper we derive
rigorous error bounds for the approximation of nonlinear operators by means of
CNN models. More precisely, we address the case in which an operator maps a
finite dimensional input onto a functional
output , and a neural network
model is used to approximate a discretized version of the input-to-output map.
The resulting error estimates provide a clear interpretation of the
hyperparameters defining the neural network architecture. All the proofs are
constructive, and they ultimately reveal a deep connection between CNNs and the
Fourier transform. Finally, we complement the derived error bounds by numerical
experiments that illustrate their application
Nonlinear model order reduction for problems with microstructure using mesh informed neural networks
Many applications in computational physics involve approximating problems
with microstructure, characterized by multiple spatial scales in their data.
However, these numerical solutions are often computationally expensive due to
the need to capture fine details at small scales. As a result, simulating such
phenomena becomes unaffordable for many-query applications, such as
parametrized systems with multiple scale-dependent features. Traditional
projection-based reduced order models (ROMs) fail to resolve these issues, even
for second-order elliptic PDEs commonly found in engineering applications. To
address this, we propose an alternative nonintrusive strategy to build a ROM,
that combines classical proper orthogonal decomposition (POD) with a suitable
neural network (NN) model to account for the small scales. Specifically, we
employ sparse mesh-informed neural networks (MINNs), which handle both spatial
dependencies in the solutions and model parameters simultaneously. We evaluate
the performance of this strategy on benchmark problems and then apply it to
approximate a real-life problem involving the impact of microcirculation in
transport phenomena through the tissue microenvironment
Mapping Drug Interactions at the Covalent Topoisomerase II-DNA Complex by Bisantrene/Amsacrine Congeners *
To identify structural determinants for the sequence-specific recognition of covalent topoisomerase II-DNA complexes by anti-cancer drugs, we investigated a number of bisantrene congeners, including a 10-azabioisoster, bearing one or two 4, 5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1, 4, or 9 of the anthracene ring system. The studied bisantrene/amsacrine (m-AMSA) hybrid and bisantrene isomers were able to poison DNA topoisomerase II with an intermediate activity between those of bisantrene and m-AMSA. Moving the side chain from the central to a lateral ring (from C-9 to C-1/C-4) only slightly modified the drug DNA affinity, whereas it dramatically affected local base preferences of poison-stimulated DNA cleavage. In contrast, switching the planar aromatic systems of bisantrene and m-AMSA did not substantially alter the sequence specificity of drug action. A computer-assisted steric and electrostatic alignment analysis of the test compounds was in agreement with the experimental data, since a common pharmacophore was shared by bisantrene, m-AMSA, and 9-substituted analogs, whereas the 1-substituted isomer showed a radically changed pharmacophoric structure. Thus, the relative space occupancy and electron distribution of putative DNA binding (aromatic rings) and enzyme binding (side chains) moieties are fundamental in directing the specific action of topoisomerase II poisons and in determining the poison pharmacophore
Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells.
The plasma membrane enzyme c-glutamyltransferase (GGT) is regarded as critical for the
maintenance of intracellular levels of glutathione (GSH). GGT expression has been implicated
in drug resistance through elevation of intracellular GSH. The dependence of intracellular
GSH on GGT expression was not conclusively ascertained. The present study was
designed to investigate the role of GGT and of intracellular GSH levels in modulating proliferation
and sensitivity to cisplatin of melanoma cells. GGT transfection resulted in
increased growth, both in vitro and in tumour xenografts. In addition, GGT-transfected cells
exhibited reduced sensitivity to cisplatin associated with lower DNA platination. A
decrease in intracellular GSH levels, rather than an increase, was observed in GGT-transfected
cells; moreover, in cysteine-deficient conditions, the expression of GGT did not provide
transfected cells with the ability of utilising extracellular GSH. In conclusion, these results
indicate that GGTactivity confers a growth advantage unrelated with intracellular glutathione
supply, and are consistent with the interpretation that cisplatin resistance is the consequence
of modifications of cellular pharmacokinetics as a result of extracellular drug
inactivation by thiol metabolites originated by GGT-mediated GSH cleavage
Learning high-order interactions for polygenic risk prediction
Within the framework of precision medicine, the stratification of individual genetic susceptibility based on inherited DNA variation has paramount relevance. However, one of the most relevant pitfalls of traditional Polygenic Risk Scores (PRS) approaches is their inability to model complex high-order non-linear SNP-SNP interactions and their effect on the phenotype (e.g. epistasis). Indeed, they incur in a computational challenge as the number of possible interactions grows exponentially with the number of SNPs considered, affecting the statistical reliability of the model parameters as well. In this work, we address this issue by proposing a novel PRS approach, called High-order Interactions-aware Polygenic Risk Score (hiPRS), that incorporates high-order interactions in modeling polygenic risk. The latter combines an interaction search routine based on frequent itemsets mining and a novel interaction selection algorithm based on Mutual Information, to construct a simple and interpretable weighted model of user-specified dimensionality that can predict a given binary phenotype. Compared to traditional PRSs methods, hiPRS does not rely on GWAS summary statistics nor any external information. Moreover, hiPRS differs from Machine Learning-based approaches that can include complex interactions in that it provides a readable and interpretable model and it is able to control overfitting, even on small samples. In the present work we demonstrate through a comprehensive simulation study the superior performance of hiPRS w.r.t. state of the art methods, both in terms of scoring performance and interpretability of the resulting model. We also test hiPRS against small sample size, class imbalance and the presence of noise, showcasing its robustness to extreme experimental settings. Finally, we apply hiPRS to a case study on real data from DACHS cohort, defining an interaction-aware scoring model to predict mortality of stage II-III Colon-Rectal Cancer patients treated with oxaliplatin
Microenvironment modulation and enhancement of antilymphoma therapy by the heparanase inhibitor roneparstat
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