Simulated Annealing for Topological Solitons

The search for solutions of field theories allowing for topological solitons requires that we find the field configuration with the lowest energy in a given sector of topological charge. The standard approach is based on the numerical solution of the static Euler-Lagrange differential equation following from the field energy. As an alternative, we propose to use a simulated annealing algorithm to minimize the energy functional directly. We have applied simulated annealing to several nonlinear classical field theories: the sine-Gordon model in one dimension, the baby Skyrme model in two dimensions and the nuclear Skyrme model in three dimensions. We describe in detail the implementation of the simulated annealing algorithm, present our results and get independent confirmation of the studies which have used standard minimization techniques.Comment: 31 pages, LaTeX, better quality pics at http://www.phy.umist.ac.uk/~weidig/Simulated_Annealing/, updated for publicatio

Statistical Physics of Design

Modern life increasingly relies on complex products that perform a variety of functions. The key difficulty of creating such products lies not in the manufacturing process, but in the design process. However, design problems are typically driven by multiple contradictory objectives and different stakeholders, have no obvious stopping criteria, and frequently prevent construction of prototypes or experiments. Such ill-defined, or "wicked" problems cannot be "solved" in the traditional sense with optimization methods. Instead, modern design techniques are focused on generating knowledge about the alternative solutions in the design space. In order to facilitate such knowledge generation, in this dissertation I develop the "Systems Physics" framework that treats the emergent structures within the design space as physical objects that interact via quantifiable forces. Mathematically, Systems Physics is based on maximal entropy statistical mechanics, which allows both drawing conceptual analogies between design problems and collective phenomena and performing numerical calculations to gain quantitative understanding. Systems Physics operates via a Model-Compute-Learn loop, with each step refining our thinking of design problems. I demonstrate the capabilities of Systems Physics in two very distinct case studies: Naval Engineering and self-assembly. For the Naval Engineering case, I focus on an established problem of arranging shipboard systems within the available hull space. I demonstrate the essential trade-off between minimizing the routing cost and maximizing the design flexibility, which can lead to abrupt phase transitions. I show how the design space can break into several locally optimal architecture classes that have very different robustness to external couplings. I illustrate how the topology of the shipboard functional network enters a tight interplay with the spatial constraints on placement. For the self-assembly problem, I show that the topology of self-assembled structures can be reliably encoded in the properties of the building blocks so that the structure and the blocks can be jointly designed. The work presented here provides both conceptual and quantitative advancements. In order to properly port the language and the formalism of statistical mechanics to the design domain, I critically re-examine such foundational ideas as system-bath coupling, coarse graining, particle distinguishability, and direct and emergent interactions. I show that the design space can be packed into a special information structure, a tensor network, which allows seamless transition from graphical visualization to sophisticated numerical calculations. This dissertation provides the first quantitative treatment of the design problem that is not reduced to the narrow goals of mathematical optimization. Using statistical mechanics perspective allows me to move beyond the dichotomy of "forward" and "inverse" design and frame design as a knowledge generation process instead. Such framing opens the way to further studies of the design space structures and the time- and path-dependent phenomena in design. The present work also benefits from, and contributes to the philosophical interpretations of statistical mechanics developed by the soft matter community in the past 20 years. The discussion goes far beyond physics and engages with literature from materials science, naval engineering, optimization problems, design theory, network theory, and economic complexity.PHDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163133/1/aklishin_1.pd

A review of population-based metaheuristics for large-scale black-box global optimization: Part B

This paper is the second part of a two-part survey series on large-scale global optimization. The first part covered two major algorithmic approaches to large-scale optimization, namely decomposition methods and hybridization methods such as memetic algorithms and local search. In this part we focus on sampling and variation operators, approximation and surrogate modeling, initialization methods, and parallelization. We also cover a range of problem areas in relation to large-scale global optimization, such as multi-objective optimization, constraint handling, overlapping components, the component imbalance issue, and benchmarks, and applications. The paper also includes a discussion on pitfalls and challenges of current research and identifies several potential areas of future research

Prescriptive formalism for constructing domain-specific evolutionary algorithms

It has been widely recognised in the computational intelligence and machine learning communities that the key to understanding the behaviour of learning algorithms is to understand what representation is employed to capture and manipulate knowledge acquired during the learning process. However, traditional evolutionary algorithms have tended to employ a fixed representation space (binary strings), in order to allow the use of standardised genetic operators. This approach leads to complications for many problem domains, as it forces a somewhat artificial mapping between the problem variables and the canonical binary representation, especially when there are dependencies between problem variables (e.g. problems naturally defined over permutations). This often obscures the relationship between genetic structure and problem features, making it difficult to understand the actions of the standard genetic operators with reference to problem-specific structures. This thesis instead advocates m..

Sequential Decision-Making for Drug Design: Towards closed-loop drug design

Drug design is a process of trial and error to design molecules with a desired response toward a biological target, with the ultimate goal of finding a new medication. It is estimated to be up to 10^{60} molecules that are of potential interest as drugs, making it a difficult problem to find suitable molecules. A crucial part of drug design is to design and determine what molecules should be experimentally tested, to determine their activity toward the biological target. To experimentally test the properties of a molecule, it has to be successfully made, often requiring a sequence of reactions to obtain the desired product. Machine learning can be utilized to predict the outcome of a reaction, helping to find successful reactions, but requires data for the reaction type of interest. This thesis presents a work that combinatorially investigates the use of active learning to acquire training data for reaching a certain level of predictive ability in predicting whether a reaction is successful or not. However, only a limited number of molecules can often be synthesized every time. Therefore, another line of work in this thesis investigates which designed molecules should be experimentally tested, given a budget of experiments, to sequentially acquire new knowledge. This is formulated as a multi-armed bandit problem and we propose an algorithm to solve this problem. To suggest potential drug molecules to choose from, recent advances in machine learning have also enabled the use of generative models to design novel molecules with certain predicted properties. Previous work has formulated this as a reinforcement learning problem with success in designing and optimizing molecules with drug-like properties. This thesis presents a systematic comparison of different reinforcement learning algorithms for string-based generation of drug molecules. This includes a study of different ways of learning from previous and current batches of samples during the iterative generation

Rigorous Computational and Experimental Investigations on MDM2/MDMX-Targeted Linear and Macrocyclic Peptides

There is interest in peptide drug design, especially for targeting intracellular protein–protein interactions. Therefore, the experimental validation of a computational platform for enabling peptide drug design is of interest. Here, we describe our peptide drug design platform (CMDInventus) and demonstrate its use in modeling and predicting the structural and binding aspects of diverse peptides that interact with oncology targets MDM2/MDMX in comparison to both retrospective (pre-prediction) and prospective (post-prediction) data. In the retrospective study, CMDInventus modules (CMDpeptide, CMDboltzmann, CMDescore and CMDyscore) were used to accurately reproduce structural and binding data across multiple MDM2/MDMX data sets. In the prospective study, CMDescore, CMDyscore and CMDboltzmann were used to accurately predict binding affinities for an Ala-scan of the stapled α-helical peptide ATSP-7041. Remarkably, CMDboltzmann was used to accurately predict the results of a novel D-amino acid scan of ATSP-7041. Our investigations rigorously validate CMDInventus and support its utility for enabling peptide drug design

The Emerging Trends of Multi-Label Learning

Exabytes of data are generated daily by humans, leading to the growing need for new efforts in dealing with the grand challenges for multi-label learning brought by big data. For example, extreme multi-label classification is an active and rapidly growing research area that deals with classification tasks with an extremely large number of classes or labels; utilizing massive data with limited supervision to build a multi-label classification model becomes valuable for practical applications, etc. Besides these, there are tremendous efforts on how to harvest the strong learning capability of deep learning to better capture the label dependencies in multi-label learning, which is the key for deep learning to address real-world classification tasks. However, it is noted that there has been a lack of systemic studies that focus explicitly on analyzing the emerging trends and new challenges of multi-label learning in the era of big data. It is imperative to call for a comprehensive survey to fulfill this mission and delineate future research directions and new applications.Comment: Accepted to TPAMI 202