In molecular dynamics (MD) simulations, free-energy differences are often calculated using free energy perturbation or thermodynamic integration (TI) methods. However, both techniques are only suited to calculate free-energy differences between two end states. Enveloping distribution sampling (EDS) presents an attractive alternative that allows to calculate multiple free-energy differences in a single simulation. In EDS, a reference state is simulated which "envelopes" the end states. The challenge of this methodology is the determination of optimal reference-state parameters to ensure equal sampling of all end states. Currently, the automatic determination of the reference-state parameters for multiple end states is an unsolved issue that limits the application of the methodology. To resolve this, we have generalised the replica-exchange EDS (RE-EDS) approach, introduced by Lee et al. [J. Chem. Theory Comput. 10, 2738 (2014)] for constant-pH MD simulations. By exchanging configurations between replicas with different reference-state parameters, the complexity of the parameter-choice problem can be substantially reduced. A new robust scheme to estimate the reference-state parameters from a short initial RE-EDS simulation with default parameters was developed, which allowed the calculation of 36 free-energy differences between nine small-molecule inhibitors of phenylethanolamine N-methyltransferase from a single simulation. The resulting free-energy differences were in excellent agreement with values obtained previously by TI and two-state EDS simulations.
Under the label of scientific metaphysics, many naturalist metaphysicians are moving away from a priori conceptual analysis and instead seek scientific explanations that will help bring forward a unified understanding of the world. This paper first reviews how our classical assumptions about ordinary objects fail to be true in light of quantum mechanics. The paper then explores how our experiences of ordinary objects arise by reflecting on how our neural system operates algorithmically. Contemporary models and simulations in computational neuroscience are shown to provide a theoretical framework that does not conflict with existing fundamental physical theories, and nonetheless helps us make sense of the manifest image. It is argued that we must largely explain how the manifest image arises in algorithmic terms, so that we can pursue a metaphysics about ordinary objects that is scientifically well founded.
Recent advances in imaging technology now provide us with 3D images of developing organs. These can be used to extract 3D geometries for simulations of organ development. To solve models on growing domains, the displacement fields between consecutive image frames need to be determined. Here we develop and evaluate different landmark-free algorithms for the determination of such displacement fields from image data. In particular, we examine minimal distance, normal distance, diffusion-based, and uniform mapping algorithms and test these algorithms with both synthetic and real data in 2D and 3D. We conclude that in most cases, the normal distance algorithm is the method of choice and wherever it fails, diffusion-based mapping provides a good alternative. ACM Reference Format:Clemens Arthur Schwaninger, Denis Menshykau, and Dagmar Iber. 2015. Simulating organogenesis: Algorithms for the image-based determination of displacement fields. ACM Trans. Model.
Block’s (The Philosophical Review, 90(1), 5–43 1981) anti-behaviourist attack of the Turing Test not only illustrates that the test is a non-sufficient criterion for attributing thought; I suggest that it also exemplifies the limiting case of the more general concern that a machine which has access to enormous amounts of data can pass the Turing Test by simple symbol-manipulation techniques. If the answers to a human interrogator are entailed by the machines’ data, the Turing Test offers no clear criterion to distinguish between a thinking machine and a machine that merely manipulates representations of words and sentences as it is found in contemporary Natural Language Processing models. This paper argues that properties about vagueness are accessible to any human-like thinker but do not normally display themselves in ordinary language use. Therefore, a machine that merely performs simple symbol manipulation from large amounts of previously acquired data – where this body of data does not contain facts about vagueness – will not be able to report on these properties. Conversely, a machine that has the capacity to think would be able to report on these properties. I argue that we can exploit this fact to establish a sufficient criterion of thought. The criterion is a specification of some of the questions that, as I explain, should be asked by the interrogator in a Turing Test situation.
Numerous species use different forms of communication in order to successfully interact in their respective environment. This article seeks to elucidate limitations of the classical conduit metaphor by investigating communication from the perspectives of biology and artificial neural networks. First, communication is a biological natural phenomenon, found to be fruitfully grounded in an organism’s embodied structures and memory system, where specific abilities are tied to procedural, semantic, and episodic long-term memory as well as to working memory. Second, the account explicates differences between non-verbal and verbal communication and shows how artificial neural networks can communicate by means of ontologically non-committal modelling. This approach enables new perspectives of communication to emerge regarding both sender and receiver. It is further shown that communication features gradient properties that are plausibly divided into a reflexive and a reflective form, parallel to knowledge and reflection.
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