62 research outputs found
Intersection types for unbind and rebind
We define a type system with intersection types for an extension of
lambda-calculus with unbind and rebind operators. In this calculus, a term with
free variables, representing open code, can be packed into an "unbound" term,
and passed around as a value. In order to execute inside code, an unbound term
should be explicitly rebound at the point where it is used. Unbinding and
rebinding are hierarchical, that is, the term can contain arbitrarily nested
unbound terms, whose inside code can only be executed after a sequence of
rebinds has been applied. Correspondingly, types are decorated with levels, and
a term has type decorated with k if it needs k rebinds in order to reduce to a
value. With intersection types we model the fact that a term can be used
differently in contexts providing different numbers of unbinds. In particular,
top-level terms, that is, terms not requiring unbinds to reduce to values,
should have a value type, that is, an intersection type where at least one
element has level 0. With the proposed intersection type system we get
soundness under the call-by-value strategy, an issue which was not resolved by
previous type systems.Comment: In Proceedings ITRS 2010, arXiv:1101.410
Reconciling positional and nominal binding
We define an extension of the simply-typed lambda calculus where two
different binding mechanisms, by position and by name, nicely coexist. In the
former, as in standard lambda calculus, the matching between parameter and
argument is done on a positional basis, hence alpha-equivalence holds, whereas
in the latter it is done on a nominal basis. The two mechanisms also
respectively correspond to static binding, where the existence and type
compatibility of the argument are checked at compile-time, and dynamic binding,
where they are checked at run-time.Comment: In Proceedings ITRS 2012, arXiv:1307.784
Cooperative effects enhance the transport properties of molecular spider teams
Molecular spiders are synthetic molecular motors based on DNA nanotechnology. While natural molecular motors have evolved towards very high efficiency, it remains a major challenge to develop efficient designs for man-made molecular motors. Inspired by biological motor proteins such as kinesin and myosin, molecular spiders comprise a body and several legs. The legs walk on a lattice that is coated with substrate which can be cleaved catalytically. We propose a molecular spider design in which n spiders form a team. Our theoretical considerations show that coupling several spiders together alters the dynamics of the resulting team significantly. Although spiders operate at a scale where diffusion is dominant, spider teams can be tuned to behave nearly ballistic, which results in fast and predictable motion. Based on the separation of time scales of substrate and product dwell times, we develop a theory which utilizes equivalence classes to coarse-grain the microstate space. In addition, we calculate diffusion coefficients of the spider teams, employing a mapping of an n-spider team to an n-dimensional random walker on a confined lattice. We validate these results with Monte Carlo simulations and predict optimal parameters of the molecular spider team architecture which makes their motion most directed and maximally predictable
Influences of Excluded Volume of Molecules on Signaling Processes on Biomembrane
We investigate the influences of the excluded volume of molecules on
biochemical reaction processes on 2-dimensional surfaces using a model of
signal transduction processes on biomembranes. We perform simulations of the
2-dimensional cell-based model, which describes the reactions and diffusion of
the receptors, signaling proteins, target proteins, and crowders on the cell
membrane. The signaling proteins are activated by receptors, and these
activated signaling proteins activate target proteins that bind autonomously
from the cytoplasm to the membrane, and unbind from the membrane if activated.
If the target proteins bind frequently, the volume fraction of molecules on the
membrane becomes so large that the excluded volume of the molecules for the
reaction and diffusion dynamics cannot be negligible. We find that such
excluded volume effects of the molecules induce non-trivial variations of the
signal flow, defined as the activation frequency of target proteins, as
follows. With an increase in the binding rate of target proteins, the signal
flow varies by i) monotonically increasing; ii) increasing then decreasing in a
bell-shaped curve; or iii) increasing, decreasing, then increasing in an
S-shaped curve. We further demonstrate that the excluded volume of molecules
influences the hierarchical molecular distributions throughout the reaction
processes. In particular, when the system exhibits a large signal flow, the
signaling proteins tend to surround the receptors to form receptor-signaling
protein clusters, and the target proteins tend to become distributed around
such clusters. To explain these phenomena, we analyze the stochastic model of
the local motions of molecules around the receptor.Comment: 31 pages, 10 figure
Modeling of cargo transport via molecular motors
The motor protein kinesin-1 plays an essential role in transporting cellular cargoes within eukaryotic cells. A group of kinesins ``walking\u27 together can cooperatively transport various cellular cargo over relatively long distances. While much is known about the transport by individual kinesin-1 molecules, very little is known about the specific mechanisms of cooperative kinesin-based transport. Here, we developed a two-dimensional stochastic model of cargo transport via multiple kinesins. The simulation focuses on the modeling of quantum dot cargoes transported along a microtubule. We found that high motor densities lead to increased run lengths, increased association times and decreased velocities, and that our stochastic model recapitulates experimental data reasonably well
The Beacon Calculus: A formal method for the flexible and concise modelling of biological systems.
Biological systems are made up of components that change their actions (and interactions) over time and coordinate with other components nearby. Together with a large state space, the complexity of this behaviour can make it difficult to create concise mathematical models that can be easily extended or modified. This paper introduces the Beacon Calculus, a process algebra designed to simplify the task of modelling interacting biological components. Its breadth is demonstrated by creating models of DNA replication dynamics, the gene expression dynamics in response to DNA methylation damage, and a multisite phosphorylation switch. The flexibility of these models is shown by adapting the DNA replication model to further include two topics of interest from the literature: cooperative origin firing and replication fork barriers. The Beacon Calculus is supported with the open-source simulator bcs (https://github.com/MBoemo/bcs.git) to allow users to develop and simulate their own models
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