Varying the resolution of the Rouse model on temporal and spatial scales: application to multiscale modelling of DNA dynamics

A multi-resolution bead-spring model for polymer dynamics is developed as a generalization of the Rouse model. A polymer chain is described using beads of variable sizes connected by springs with variable spring constants. A numerical scheme which can use different timesteps to advance the positions of different beads is presented and analyzed. The position of a particular bead is only updated at integer multiples of the timesteps associated with its connecting springs. This approach extends the Rouse model to a multiscale model on both spatial and temporal scales, allowing simulations of localized regions of a polymer chain with high spatial and temporal resolution, while using a coarser modelling approach to describe the rest of the polymer chain. A method for changing the model resolution on-the-fly is developed using the Metropolis-Hastings algorithm. It is shown that this approach maintains key statistics of the end-to-end distance and diffusion of the polymer filament and makes computational savings when applied to a model for the binding of a protein to the DNA filament.Comment: Submitted to Multiscale Modeling and Simulatio

Molecular Discreteness in Reaction-Diffusion Systems Yields Steady States Not Seen in the Continuum Limit

We investigate the effects of spatial discreteness of molecules in reaction-diffusion systems. It is found that discreteness within the so called Kuramoto length can lead to a localization of molecules, resulting in novel steady states that do not exist in the continuous case. These novel states are analyzed theoretically as the fixed points of accelerated localized reactions, an approach that was verified to be in good agreement with stochastic particle simulations. The relevance of this discreteness-induced state to biological intracellular processes is discussed.Comment: 5 pages, 3 figures, revtex

Stable Position Measurement of a Moving Airplane by Adaptive Camera Control

ABSTRACT-A method is developed to identify a taxiing airplane and measure its position correctly under various lighting and weather conditions by inputting a moving image from an adaptively-controlled camera into an image processor and analyzing the image in order t

Search for 60Ni excesses in MET-78008 ureilite: An ion microprobe study

We have developed a technique for in-situ Ni isotopic analysis using the ion microprobe, in order to detect ^Ni excess from the decay of the short lived nuclide ^Fe (half life=1.5Ma) in ureilite samples. The silicate minerals from MET-78008 ureilite with an old U-Pb age of 4.563±0.006 Ga were analyzed. The ^Fe/^Ni ratios of olivine and orthopyroxene are between 2700 and 5400. In spite of the high Fe/Ni ratios, we could not observe any detectable ^Ni excess. From the mean value of olivine core data, we obtain an upper limit of the ^Fe/^Fe ratio at the time of ureilite formation of 1.8×10^. The time difference between CAI formation and ureilite formation was estimated to be more than 4 million years, which is consistent with the UPb data from the same meteorite. We concluded that the impact event for the disruption of the ureilite parent body happened more than 4 million years after CAI formation. However, a large uncertainty in the initial ^Fe/^Fe ratio is introduced by the possibility that the ^Ni excess observed in CAIs is of nucleosynthetic origin. Our conclusion may change if the initial ^Fe/^Fe ratio of the solar system using CAI data is too high

Complex Intramolecular Mechanics of G-actin - An Elastic Network Study

Systematic numerical investigations of conformational motions in single actin molecules were performed by employing a simple elastic-network (EN) model of this protein. Similar to previous investigations for myosin, we found that G-actin essentially behaves as a strain sensor, responding by well-defined domain motions to mechanical perturbations. Several sensitive residues within the nucleotide-binding pocket (NBP) could be identified, such that the perturbation of any of them can induce characteristic flattening of actin molecules and closing of the cleft between their two mobile domains. Extending the EN model by introduction of a set of breakable links which become effective only when two domains approach one another, it was observed that G-actin can possess a metastable state corresponding to a closed conformation and that a transition to this state can be induced by appropriate perturbations in the NBP region. The ligands were roughly modeled as a single particle (ADP) or a dimer (ATP), which were placed inside the NBP and connected by elastic links to the neighbors. Our approximate analysis suggests that, when ATP is present, it stabilizes the closed conformation of actin. This may play an important role in the explanation why, in the presence of ATP, the polymerization process is highly accelerated

Switching Dynamics in Reaction Networks Induced by Molecular Discreteness

To study the fluctuations and dynamics in chemical reaction processes, stochastic differential equations based on the rate equation involving chemical concentrations are often adopted. When the number of molecules is very small, however, the discreteness in the number of molecules cannot be neglected since the number of molecules must be an integer. This discreteness can be important in biochemical reactions, where the total number of molecules is not significantly larger than the number of chemical species. To elucidate the effects of such discreteness, we study autocatalytic reaction systems comprising several chemical species through stochastic particle simulations. The generation of novel states is observed; it is caused by the extinction of some molecular species due to the discreteness in their number. We demonstrate that the reaction dynamics are switched by a single molecule, which leads to the reconstruction of the acting network structure. We also show the strong dependence of the chemical concentrations on the system size, which is caused by transitions to discreteness-induced novel states.Comment: 11 pages, 5 figure

Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation

Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but the metastases were improved by 150 mg daily erlotinib. We investigated the plasma and CSF concentrations of erlotinib at each dose as well as the correlation between the plasma and CSF concentrations of erlotinib