Probing the Mechanisms of Fibril Formation Using Lattice Models

Using exhaustive Monte Carlo simulations we study the kinetics and mechanism of fibril formation using lattice models as a function of temperature and the number of chains. While these models are, at best, caricatures of peptides, we show that a number of generic features thought to govern fibril assembly are present in the toy model. The monomer, which contains eight beads made from three letters (hydrophobic, polar, and charged), adopts a compact conformation in the native state. The kinetics of fibril assembly occurs in three distinct stages. In each stage there is a cascade of events that transforms the monomers and oligomers to ordered structures. In the first "burst" stage highly mobile oligomers of varying sizes form. The conversion to the aggregation-prone conformation occurs within the oligomers during the second stage. As time progresses, a dominant cluster emerges that contains a majority of the chains. In the final stage, the aggregation-prone conformation particles serve as a template onto which smaller oligomers or monomers can dock and undergo conversion to fibril structures. The overall time for growth in the latter stages is well described by the Lifshitz-Slyazov growth kinetics for crystallization from super-saturated solutions.Comment: 27 pages, 6 figure

Pion photoproduction off the proton in a gauge-invariant chiral unitary framework

We investigate pion photoproduction off the proton in a manifestly gauge-invariant chiral unitary extension of chiral perturbation theory. In a first step, we consider meson-baryon scattering taking into account all next-to-leading order contact interactions. The resulting low-energy constants are determined by a fit to s-wave pion-nucleon scattering and the low-energy data for the reaction pi- p --> eta n. To assess the theoretical uncertainty, we perform two different fit strategies. Having determined the low-energy constants, we then analyse the data on the s-wave multipole amplitudes E0+ of pion and eta photoproduction. These are parameter-free predictions, as the two new low-energy constants are determined by the neutron and proton magnetic moments.Comment: 23 pages, 17 figure

Disorder-induced microscopic magnetic memory

Using coherent x-ray speckle metrology, we have measured the influence of disorder on major loop return point memory (RPM) and complementary point memory (CPM) for a series of perpendicular anisotropy Co/Pt multilayer films. In the low disorder limit, the domain structures show no memory with field cycling--no RPM and no CPM. With increasing disorder, we observe the onset and the saturation of both the RPM and the CPM. These results provide the first direct ensemble-sensitive experimental study of the effects of varying disorder on microscopic magnetic memory and are compared against the predictions of existing theories.Comment: 4 pages, 4 figures. Accepted for publication in Physical Review Letters in Nov. 200

Disorder-induced magnetic memory: Experiments and theories

Beautiful theories of magnetic hysteresis based on random microscopic disorder have been developed over the past ten years. Our goal was to directly compare these theories with precise experiments. We first developed and then applied coherent x-ray speckle metrology to a series of thin multilayer perpendicular magnetic materials. To directly observe the effects of disorder, we deliberately introduced increasing degrees of disorder into our films. We used coherent x-rays to generate highly speckled magnetic scattering patterns. The apparently random arrangement of the speckles is due to the exact configuration of the magnetic domains in the sample. In effect, each speckle pattern acts as a unique fingerprint for the magnetic domain configuration. Small changes in the domain structure change the speckles, and comparison of the different speckle patterns provides a quantitative determination of how much the domain structure has changed. How is the magnetic domain configuration at one point on the major hysteresis loop related to the configurations at the same point on the loop during subsequent cycles? The microscopic return-point memory(RPM) is partial and imperfect in the disordered samples, and completely absent when the disorder was not present. We found the complementary-point memory(CPM) is also partial and imperfect in the disordered samples and completely absent when the disorder was not present. We found that the RPM is always a little larger than the CPM. We also studied the correlations between the domains within a single ascending or descending loop. We developed new theoretical models that do fit our experiments.Comment: 26 pages, 25 figures, Accepted by Physical Review B 01/25/0

Molecular Electroporation and the Transduction of Oligoarginines

Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.Comment: 15 pages, 5 figure

An automated approach for annual layer counting in ice cores

A novel method for automated annual layer counting in seasonally-resolved paleoclimate records has been developed. It relies on algorithms from the statistical framework of hidden Markov models (HMMs), which originally was developed for use in machine speech recognition. The strength of the layer detection algorithm lies in the way it is able to imitate the manual procedures for annual layer counting, while being based on statistical criteria for annual layer identification. The most likely positions of multiple layer boundaries in a section of ice core data are determined simultaneously, and a probabilistic uncertainty estimate of the resulting layer count is provided, ensuring an objective treatment of ambiguous layers in the data. Furthermore, multiple data series can be incorporated and used simultaneously. In this study, the automated layer counting algorithm has been applied to two ice core records from Greenland: one displaying a distinct annual signal and one which is more challenging. The algorithm shows high skill in reproducing the results from manual layer counts, and the resulting timescale compares well to absolute-dated volcanic marker horizons where these exist

"The dearest of our possessions": applying Floridi's information privacy concept in models of information behavior and information literacy

This conceptual paper argues for the value of an approach to privacy in the digital information environment informed by Luciano Floridi's philosophy of information and information ethics. This approach involves achieving informational privacy, through the features of anonymity and obscurity, through an optimal balance of ontological frictions. This approach may be used to modify models for information behavior and for information literacy, giving them a fuller and more effective coverage of privacy issues in the infosphere. For information behavior, the Information Seeking and Communication Model, and the Information Grounds conception, are most appropriate for this purpose. For information literacy, the metaliteracy model, using a modification a privacy literacy framework, is most suitable

Transient behavior in Single-File Systems

We have used Monte-Carlo methods and analytical techniques to investigate the influence of the characteristics, such as pipe length, diffusion, adsorption, desorption and reaction rates on the transient properties of Single-File Systems. The transient or the relaxation regime is the period in which the system is evolving to equilibrium. We have studied the system when all the sites are reactive and when only some of them are reactive. Comparisons between Mean-Field predictions, Cluster Approximation predictions, and Monte Carlo simulations for the relaxation time of the system are shown. We outline the cases where Mean-Field analysis gives good results compared to Dynamic Monte-Carlo results. For some specific cases we can analytically derive the relaxation time. Occupancy profiles for different distribution of the sites both for Mean-Field and simulations are compared. Different results for slow and fast reaction systems and different distribution of reactive sites are discussed.Comment: 18 pages, 19 figure

Finite size effects on thermal denaturation of globular proteins

Finite size effects on the cooperative thermal denaturation of proteins are considered. A dimensionless measure of cooperativity, Omega, scales as N^zeta, where N is the number of amino acids. Surprisingly, we find that zeta is universal with zeta = 1 + gamma, where the exponent gamma characterizes the divergence of the susceptibility for a self-avoiding walk. Our lattice model simulations and experimental data are consistent with the theory. Our finding rationalizes the marginal stability of proteins and substantiates the earlier predictions that the efficient folding of two-state proteins requires the folding transition temperature to be close to the collapse temperature.Comment: 3 figures. Physical Review Letters (in press