An Ensemble Kalman-Particle Predictor-Corrector Filter for Non-Gaussian Data Assimilation

An Ensemble Kalman Filter (EnKF, the predictor) is used make a large change in the state, followed by a Particle Filer (PF, the corrector) which assigns importance weights to describe non-Gaussian distribution. The weights are obtained by nonparametric density estimation. It is demonstrated on several numerical examples that the new predictor-corrector filter combines the advantages of the EnKF and the PF and that it is suitable for high dimensional states which are discretizations of solutions of partial differential equations.Comment: ICCS 2009, to appear; 9 pages; minor edit

Identifying Membrane Lateral Organization by Contrast-Matched Small Angle Neutron Scattering

Lipid domains in model membranes are routinely studied to provide insight into the physical interactions that drive raft formation in cellular membranes. Using small angle neutron scattering, contrast-matching techniques enable the detection of lipid domains ranging from tens to hundreds of nanometers which are not accessible to other techniques without the use of extrinsic probes. Here, we describe a probe-free experimental approach and model-free analysis to identify lipid domains in freely floating vesicles of ternary phase separating lipid mixtures

Mitocans induce lipid flip-flop and permeabilize the membrane to signal apoptosis

Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and x-ray scattering in combination with calcein leakage assays to characterize the effects of PST, NRC, and tamoxifen (TAM) on a biomimetic model membrane. We report an increase in lipid flip-flop half-times (t1/2) (≈12.0%, ≈35.1%, and a decrease of ≈45.7%) with 2 mol percent PST, NRC, and TAM respectively. An increase in bilayer thickness (≈6.3%, ≈7.8%, and ≈7.8%) with 2 mol percent PST, NRC, and TAM, respectively, was also observed. Lastly, increases in membrane leakage (≈31.7%, ≈37.0%, and ≈34.4%) with 2 mol percent PST, NRC, and TAM, respectively, were seen. Considering the maintenance of an asymmetric lipid composition across the outer mitochondrial membrane (OMM) is crucial to eukaryotic cellular homeostasis and survival, our results suggest PST and NRC may play a role in disrupting the native distribution of lipids within the OMM. A possible mechanism of action for PST- and NRC-induced mitochondrial apoptosis is proposed via the redistribution of the native OMM lipid organization and through OMM permeabilization

Vitamin e Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in PUFA-based lipid mixtures. The influence of α-tocopherol, ?-tocopherol, and α-tocopherylquinone on the lateral organization of a 1:1 lipid mixture of saturated distearoylphosphatidylcholine (DSPC) and polyunsaturated palmitoyl-linoleoylphosphatidylcholine (PLiPC) with cholesterol provides a complement to our growing understanding of the influence of tocopherol on lipid phases. Characterization of domain melting suggests a slight depression in the transition temperature and a decrease in transition cooperativity. Tocopherol concentrations that are an order of magnitude higher than anticipated physiological concentrations (2 mol percent) do not significantly perturb lipid domains; however, addition of 10 mol percent is able to destabilize domains and promote lipid mixing. In contrast to this behavior, increasing concentrations of the oxidized product of α-tocopherol (α-tocopherylquinone) induces a proportional increase in domain stabilization. We speculate how the contrasting effect of the oxidized product may supplement the antioxidant response of vitamin E

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics

© 2019 Biophysical Society Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies

Time-resolved SANS reveals pore-forming peptides cause rapid lipid reorganization

Cells depend on proper lipid transport and their precise distribution for vital cellular function. Disruption of such lipid organization can be initiated by external agents to cause cell death. Here, we investigate two antimicrobial pore-forming peptides, alamethicin and melittin, and their influence on lipid intervesicular exchange and transverse lipid diffusion (i.e. flip-flop) in model lipid vesicles. Small angle neutron scattering (SANS) and a strategic contrast matching scheme show the mixing of two isotopically distinct dimyristoylphosphocholine (DMPC) vesicle populations is promoted upon the addition of high (1/40) and low (1/150, 1/1000) peptide-to-lipid (P/L) molar ratios. Parsing out the individual exchange and flip-flop rate constants revealed that alamethicin increases both DMPC flip-flop and exchange by ≈2-fold when compared to methanol alone (the carrier solvent of the peptides). On the other hand, melittin affected DMPC flip-flop by a factor of 1 to 4 depending on the concentration, but had little effect on inter-vesicle lipid exchange at low P/L ratios. Thermodynamic parameters measured at high protein concentrations (P/L = 1/40) yielded remarkable similarity in the values obtained for both peptides, indicating likeness in their mechanism of action on lipid motion despite differences in their proposed oligomeric pore structures. The entropic contributions to the free energy of activation became favorable upon peptide addition, while the enthalpy of activation remained the major barrier to lipid exchange and flip-flop. This journal i

The effect of the annealing temperature on the local distortion of La0.67_{0.67}Ca0.33_{0.33}MnO3_3 thin films

Mn $K$-edge fluorescence data are presented for thin film samples (3000~\AA) of Colossal Magnetoresistive (CMR) La$_{0.67}$Ca$_{0.33}$MnO$_3$: as-deposited, and post-annealed at 1000 K and 1200 K. The local distortion is analyzed in terms of three contributions: static, phonon, and an extra, temperature-dependent, polaron term. The polaron distortion is very small for the as-deposited sample and increases with the annealing temperature. In contrast, the static distortion in the samples decreases with the annealing temperature. Although the local structure of the as-deposited sample shows very little temperature dependence, the change in resistivity with temperature is the largest of these three thin film samples. The as-deposited sample also has the highest magnetoresistance (MR), which indicates some other mechanism may also contribute to the transport properties of CMR samples. We also discuss the relationship between local distortion and the magnetization of the sample.Comment: 11 pages of Preprint format, 8 figures in one tar fil

Transverse lipid organization dictates bending fluctuations in model plasma membranes

© 2020 The Royal Society of Chemistry. Membrane undulations play a vital role in many biological processes, including the regulation of membrane protein activity. The asymmetric lipid composition of most biological membranes complicates theoretical description of these bending fluctuations, yet experimental data that would inform any such a theory is scarce. Here, we used neutron spin-echo (NSE) spectroscopy to measure the bending fluctuations of large unilamellar vesicles (LUV) having an asymmetric transbilayer distribution of high- and low-melting lipids. The asymmetric vesicles were prepared using cyclodextrin-mediated lipid exchange, and were composed of an outer leaflet enriched in egg sphingomyelin (ESM) and an inner leaflet enriched in 1-palmitoyl-2-oleoyl-phosphoethanolamine (POPE), which have main transition temperatures of 37 °C and 25 °C, respectively. The overall membrane bending rigidity was measured at three temperatures: 15 °C, where both lipids are in a gel state; 45 °C, where both lipids are in a fluid state; and 30 °C, where there is gel-fluid co-existence. Remarkably, the dynamics for the fluid asymmetric LUVs (aLUVs) at 30 °C and 45 °C do not follow trends predicted by their symmetric counterparts. At 30 °C, compositional asymmetry suppressed the bending fluctuations, with the asymmetric bilayer exhibiting a larger bending modulus than that of symmetric bilayers corresponding to either the outer or inner leaflet. We conclude that the compositional asymmetry and leaflet coupling influence the internal dissipation within the bilayer and result in membrane properties that cannot be directly predicted from corresponding symmetric bilayers

Statistical Analysis of Composite Spectra

We consider nearest neighbor spacing distributions of composite ensembles of levels. These are obtained by combining independently unfolded sequences of levels containing only few levels each. Two problems arise in the spectral analysis of such data. One problem lies in fitting the nearest neighbor spacing distribution to the histogram of level spacings obtained from the data. We show that the method of Bayesian inference is superior to this procedure. The second problem occurs when one unfolds such short sequences. We show that the unfolding procedure generically leads to an overestimate of the chaoticity parameter. This trend is absent in the presence of long-range level correlations. Thus, composite ensembles of levels from a system with long-range spectral stiffness yield reliable information about the chaotic behavior of the system.Comment: 26 pages, 3 figures; v3: changed conclusions, appendix adde

The antioxidant vitamin E as a membrane raft modulator: Tocopherols do not abolish lipid domains

© 2020 Elsevier B.V. The antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour. Here, we studied the influence of vitamin E and some of its vitamers on membrane raft stability using phase separating unilamellar lipid vesicles in conjunction with small-angle scattering techniques and fluorescence microscopy. We find that lipid phase behaviour remains unperturbed well beyond physiological concentrations of vitamin E (up to a mole fraction of 0.10). Our results are consistent with a proposed line active role of vitamin E at the domain boundary. We discuss the implications of these findings as they pertain to lipid raft modification in native membranes, and propose a new hypothesis for the antioxidant mechanism of vitamin E