A wildland fire model with data assimilation

A wildfire model is formulated based on balance equations for energy and fuel, where the fuel loss due to combustion corresponds to the fuel reaction rate. The resulting coupled partial differential equations have coefficients that can be approximated from prior measurements of wildfires. An ensemble Kalman filter technique with regularization is then used to assimilate temperatures measured at selected points into running wildfire simulations. The assimilation technique is able to modify the simulations to track the measurements correctly even if the simulations were started with an erroneous ignition location that is quite far away from the correct one.Comment: 35 pages, 12 figures; minor revision January 2008. Original version available from http://www-math.cudenver.edu/ccm/report

The kinetic fragility of liquids as manifestation of the elastic softening

We show that the fragility $m$, the steepness of the viscosity and relaxation time close to the vitrification, increases with the degree of elastic softening, i.e. the decrease of the elastic modulus with increasing temperature, in universal way. This provides a novel connection between the thermodynamics, via the modulus, and the kinetics. The finding is evidenced by numerical simulations and comparison with the experimental data of glassformers with widely different fragilities ($33 \le m \le 115$), leading to a fragility-independent elastic master curve extending over eighteen decades in viscosity and relaxation time. The master curve is accounted for by a cavity model pointing out the roles of both the available free volume and the cage softness. A major implication of our findings is that ultraslow relaxations, hardly characterised experimentally, become predictable by linear elasticity. As an example, the viscosity of supercooled silica is derived over about fifteen decades with no adjustable parameters.Comment: 7 pages, 6 figures; Added new results, improved the theoretical sectio

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Factors That Drive Peptide Assembly and Fibril Formation: Experimental and Theoretical Analysis of Sup35 NNQQNY Mutants

Residue mutations have substantial effects on aggregation kinetics and propensities of amyloid peptides and their aggregate morphologies. Such effects are attributed to conformational transitions accessed by various types of oligomers such as steric zipper or single β-sheet. We have studied the aggregation propensities of six NNQQNY mutants: NVVVVY, NNVVNV, NNVVNY, VIQVVY, NVVQIY, and NVQVVY in water using a combination of ion-mobility mass spectrometry, transmission electron microscopy, atomic force microscopy, and all-atom molecular dynamics simulations. Our data show a strong correlation between the tendency to form early β-sheet oligomers and the subsequent aggregation propensity. Our molecular dynamics simulations indicate that the stability of a steric zipper structure can enhance the propensity for fibril formation. Such stability can be attained by either hydrophobic interactions in the mutant peptide or polar side-chain interdigitations in the wild-type peptide. The overall results display only modest agreement with the aggregation propensity prediction methods such as PASTA, Zyggregator, and RosettaProfile, suggesting the need for better parametrization and model peptides for these algorithms

Conformational dynamics of alpha-synuclein:insights from mass spectrometry

The aggregation and deposition of alpha-synuclein in Lewy bodies is associated with the progression of Parkinson's disease. Here, Mass Spectrometry (MS) is used in combination with Ion Mobility (IM), chemical crosslinking and Electron Capture Dissociation (ECD) to probe transient structural elements of alpha-synuclein and its oligomers. Each of these reveals different aspects of the conformational heterogeneity of this 14 kDa protein. IM-MS analysis indicates that this protein is highly disordered, presenting in positive ionisation mode with a charge state range of 5 <= z <= 21 for the monomer, along with a collision cross section range of similar to 1600 angstrom(2)). Chemical crosslinking applied in conjunction with IM-MS captures solution phase conformational families enabling comparison with those exhibited in the gas phase. Crosslinking IM-MS identifies 3 distinct conformational families, Compact (similar to 1200 angstrom(2)), Extended (similar to 1500 angstrom(2)) and Unfolded (similar to 2350 angstrom(2)) which correlate with those observed in solution. ECD-Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry (ECD-FT-ICR MS) highlights the effect of pH on alpha-synuclein structure, identifying the conformational flexibility of the N and C termini as well as providing evidence for structure in the core and at times the C terminus. A hypothesis is proposed for the variability displayed in the structural rearrangement of alpha-synuclein following changes in solution pH. Following a 120 h aggregation time course, we observe an increase in the ratio of dimer to monomer, but no gross conformational changes in either, beyond the significant variations that are observed day-to-day from this conformationally dynamic protein

Free-energy effects in single-molecule polymer crystals

The paper presents extensive MD simulations of the crystallization process of a single polyethylene chain with N = 500 monomers. It is shown that the folding process involves intermediate metastable crystalline states, in analogy with the experiments, and ends up in a equilibrated. i.e. not kinetically selected, lamella with ten stems of approximately equal length, arranged into a regular, hexagonal pattern. The free-energy landscape is presented and the different energy and entropy contributions, the latter mostly due to surface rearrangements, discussed. (c) 2006 Elsevier B.V. All rights reserved

A manifestation of the Ostwald step rule: Molecular-dynamics simulations and free-energy landscape of the primary nucleation and melting of single-molecule polyethylene in dilute solution

The paper presents numerical results from extensive molecular-dynamics simulations of the crystallization process of a single polyethylene chain with N=500 monomers. The development of the ordered structure is seen to proceed along different routes involving either the global reorganization of the chain or, alternatively, well-separated connected nuclei. No dependence on the thermal history was observed at the late stages of the crystallization. The folding process involves several intermediate ordered metastable states, in strong analogy with the experiments, and ends up in a well-defined long-lived lamella with ten stems of approximately equal length, arranged into a regular, hexagonal pattern. This behavior may be seen as a microscopic manifestation of the Ostwald step rule. Both the metastable states and the long-lived one are evidenced as the local minima and the global one of the free-energy landscape, respectively. The study of the microscopic organization of the lamella evidenced that the two caps are rather flat, i.e., the loops connecting the stems are short. Interestingly, annealing the chain through the different metastable states leaves the average number of monomers per loop nearly unchanged. It is also seen that the chain ends, the so-called cilia, are localized on the surface of the lamella, in agreement with the experiments, and that structural fluctuations take place on the lamella surface, as noted by recent Monte Carlo simulations. The study of the melting process evidences that the degree of hysteresis is small