Learning to integrate reactivity and deliberation in uncertain planning and scheduling problems

This paper describes an approach to planning and scheduling in uncertain domains. In this approach, a system divides a task on a goal by goal basis into reactive and deliberative components. Initially, a task is handled entirely reactively. When failures occur, the system changes the reactive/deliverative goal division by moving goals into the deliberative component. Because our approach attempts to minimize the number of deliberative goals, we call our approach Minimal Deliberation (MD). Because MD allows goals to be treated reactively, it gains some of the advantages of reactive systems: computational efficiency, the ability to deal with noise and non-deterministic effects, and the ability to take advantage of unforseen opportunities. However, because MD can fall back upon deliberation, it can also provide some of the guarantees of classical planning, such as the ability to deal with complex goal interactions. This paper describes the Minimal Deliberation approach to integrating reactivity and deliberation and describe an ongoing application of the approach to an uncertain planning and scheduling domain

Optimal control in heterogeneous domain decomposition methods

Some new domain decomposition methods (DDM) based on optimal control approach are introduced for the coupling of first- and second-order equations on overlapping subdomains. Several cost functionals and control functions are proposed. Uniqueness and existence results are proved for the coupled problem and the convergence of iterative processes is analyze

From residue coevolution to protein conformational ensembles and functional dynamics

The analysis of evolutionary amino acid correlations has recently attracted a surge of renewed interest, also due to their successful use in de novo protein native structure prediction. However, many aspects of protein function, such as substrate binding and product release in enzymatic activity, can be fully understood only in terms of an equilibrium ensemble of alternative structures, rather than a single static structure. In this paper we combine coevolutionary data and molecular dynamics simulations to study protein conformational heterogeneity. To that end, we adapt the Boltzmann-learning algorithm to the analysis of homologous protein sequences and develop a coarse-grained protein model specifically tailored to convert the resulting contact predictions to a protein structural ensemble. By means of exhaustive sampling simulations, we analyze the set of conformations that are consistent with the observed residue correlations for a set of representative protein domains, showing that (i) the most representative structure is consistent with the experimental fold and (ii) the various regions of the sequence display different stability, related to multiple biologically relevant conformations and to the cooperativity of the coevolving pairs. Moreover, we show that the proposed protocol is able to reproduce the essential features of a protein folding mechanism as well as to account for regions involved in conformational transitions through the correct sampling of the involved conformers

Numerical simulation of residual stresses induced by weld repair in a stainless steel pipe considering the influence of an initial fabrication weld

This work presents the application of a finite element (FE) model developed to simulate the repair process in the case of components with a pre-existing stress state. The approach is tested in the case of a repair of a laser beam weld in a stainless steel pipe with the region of repair located in the heat affected zone of the original weld. The area of the repair is removed and refilled testing different approaches in terms of the number, and direction of the repair passes. The comparison between the refilling procedures is presented with the aim of evaluating the effects on the final residual stress distribution

Chelation therapy to prevent diabetes-associated cardiovascular events

Purpose of review For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD. Recent findings This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis. Summary In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients

Numerical simulation of residual stresses induced by weld repair in a stainless steel pipe considering the influence of an initial fabrication weld

This work presents the application of a finite element (FE) model developed to simulate the repair process in the case of components with a pre-existing stress state. The approach is tested in the case of a repair of a laser beam weld in a stainless steel pipe with the region of repair located in the heat affected zone of the original weld. The area of the repair is removed and refilled testing different approaches in terms of the number, and direction of the repair passes. The comparison between the refilling procedures is presented with the aim of evaluating the effects on the final residual stress distribution

A matrix–free high–order solver for the numerical solution of cardiac electrophysiology

We propose a matrix-free solver for the numerical solution of the cardiac electrophysiology model consisting of the monodomain nonlinear reaction-diffusion equation coupled with a system of ordinary differential equations for the ionic species. Our numerical approximation is based on the high-order Spectral Element Method (SEM) to achieve accurate numerical discretization while employing a much smaller number of Degrees of Freedom than first-order Finite Elements. We combine vectorization with sum- factorization, thus allowing for a very efficient use of high-order polynomials in a high performance computing framework. We validate the effectiveness of our matrix-free solver in a variety of applications and perform different electrophysiological simulations ranging from a simple slab of cardiac tissue to a realistic four-chamber heart geometry. We compare SEM to SEM with Numerical Integration (SEM-NI), showing that they provide comparable results in terms of accuracy and efficiency. In both cases, increasing the local polynomial degree p leads to better numerical results and smaller computational times than reducing the mesh size h. We also implement a matrix-free Geometric Multigrid preconditioner that results in a comparable number of linear solver iterations with respect to a state-of-the-art matrix-based Algebraic Multigrid preconditioner. As a matter of fact, the matrix-free solver proposed here yields up to 45x speed-up with respect to a conventional matrix-based solver. (c) 2023 Elsevier Inc. All rights reserved

Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations

p38α is a Ser/Thr protein kinase involved in a variety of cellular processes and pathological conditions, which makes it a promising pharmacological target. Although the activity of the enzyme is highly regulated, its molecular mechanism of activation remains largely unexplained, even after decades of research. By using state-of-the-art molecular dynamics simulations, we decipher the key elements of the complex molecular mechanism refined by evolution to allow for a fine tuning of p38α kinase activity. Our study describes for the first time the molecular effects of different regulators of the enzymatic activity, and provides an integrative picture of the activation mechanism that explains the seemingly contradictory X-ray and NMR data