Interactions of poly(amidoamine) dendrimers with Survanta lung surfactant: the importance of lipid domains

The interaction of generation 5 (G5) and 7 (G7) poly(amidoamine) (PAMAM) dendrimers with mica-supported Survanta bilayers is studied with atomic force microscopy (AFM). In these experiments, Survanta forms distinct gel and fluid domains with differing lipid composition. Nanoscale defects are induced by the PAMAM dendrimers. The positively charged dendrimers remove lipid from the fluid domains at a significantly greater rate than for the gel domains. Dendrimer accumulation on lipid edges and terraces preceding lipid removal has been directly imaged. Immediately following lipid removal, the mica surface is clean, indicating that lipid defects are not induced by dendrimers binding to the mica substrate and displacing the lipid.     

Poly(amidoamine) dendrimers on lipid bilayers I: Free energy and conformation of binding

Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated approaching 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayers with fully atomistic molecular dynamics, which enables the calculation of a free energy profile along the approach coordinate. Three different dendrimer terminations are examined: protonated primary amine, uncharged acetamide, and deprotonated carboxylic acid. As the dendrimer and lipids become closer, their attractive force increases (up to 240 pN) and the dendrimer becomes deformed as it interacts with the lipids. The total energy release upon binding of a G3-NH3+, G3-Ac, or G3-COO- dendrimer to a DMPC bilayer is, respectively, 36, 26, or 47 kcal/mol or, equivalently, 5.2, 3.2, or 4.7x10(-3) kcal/g. These results are analyzed in terms of the dendrimers' size, shape, and atomic distributions as well as proximity of individual lipid molecules and particular lipid atoms to the dendrimer. For example, an area of 9.6, 8.2, or 7.9 nm2 is covered on the bilayer for the G3-NH3+, G3-Ac, or G3-COO- dendrimers, respectively, while interacting strongly with 18-13 individual lipid molecules.     

Quantum state-resolved CO2 collisions at the gas-liquid interface: surface temperature-dependent scattering dynamics

Energy transfer dynamics at the gas-liquid interface are investigated as a function of surface temperature both by experimental studies of CO2 + perfluorinated polyether (PFPE) and by molecular dynamics simulations of CO2 + fluorinated self-assembled monolayers (F-SAMs). Using a normal incident molecular beam, the experimental studies probe scattered CO2 internal-state and translational distributions with high resolution infrared spectroscopy. At low incident energies [Einc = 1.6(1) kcal/mol], CO2 J-state populations and transverse Doppler velocity distributions are characteristic of the surface temperature (Trot approximately Ttrans approximately TS) over the range from 232 to 323 K. In contrast, the rotational and translational distributions at high incident energies [Einc = 10.6(8) kcal/mol] show evidence for both trapping-desorption (TD) and impulsive scattering (IS) events. Specifically, the populations are surprisingly well-characterized by a sum of Boltzmann distributions where the two components include one (TD) that equilibrates with the surface (TTD approximately TS) and a second (IS) that is much hotter than the surface temperature (TIS > TS). Support for the superthermal, yet Boltzmann, nature of the IS channel is provided by molecular dynamics (MD) simulations of CO2 + F-SAMs [Einc = 10.6 kcal/mol], which reveal two-temperature distributions, sticking probabilities, and angular distributions in near quantitative agreement with the experimental PFPE results. Finally, experiments as a function of surface temperature reveal an increase in both sticking probability and rotational/translational temperature of the IS component. Such a trend is consistent with increased surface roughness at higher surface temperature, which increases the overall probability of trapping, yet preferentially leads to impulsive scattering of more highly internally excited CO2 from the surface.     

Expansion,random walks and sieving in $$S{L_2}({\mathbb{F}_p}[t])$$

We construct new examples of expander Cayley graphs of finite groups, arising as congruence quotients of non-elementary subgroups of \(S{L_2}({\mathbb{F}_p}[t])\) modulo certain square-free ideals. We describe some applications of our results to simple random walks on such subgroups, specifically giving bounds on the rate of escape of such walks from algebraic subvarieties, the set of squares and the set of elements with reducible characteristic polynomial in \(S{L_2}({\mathbb{F}_p}[t])\).     

Quantification of Lysine Acetylation and Succinylation Stoichiometry in Proteins Using Mass Spectrometric Data-Independent Acquisitions (SWATH)

Post-translational modification of lysine residues by N_?-acylation is an important regulator of protein function. Many large-scale protein acylation studies have assessed relative changes of lysine acylation sites after antibody enrichment using mass spectrometry-based proteomics. Although relative acylation fold-changes are important, this does not reveal site occupancy, or stoichiometry, of individual modification sites, which is critical to understand functional consequences. Recently, methods for determining lysine acetylation stoichiometry have been proposed based on ratiometric analysis of endogenous levels to those introduced after quantitative per-acetylation of proteins using stable isotope-labeled acetic anhydride. However, in our hands, we find that these methods can overestimate acetylation stoichiometries because of signal interferences when endogenous levels of acylation are very low, which is especially problematic when using MS1 scans for quantification. In this study, we sought to improve the accuracy of determining acylation stoichiometry using data-independent acquisition (DIA). Specifically, we use SWATH acquisition to comprehensively collect both precursor and fragment ion intensity data. The use of fragment ions for stoichiometry quantification not only reduces interferences but also allows for determination of site-level stoichiometry from peptides with multiple lysine residues. We also demonstrate the novel extension of this method to measurements of succinylation stoichiometry using deuterium-labeled succinic anhydride. Proof of principle SWATH acquisition studies were first performed using bovine serum albumin for both acetylation and succinylation occupancy measurements, followed by the analysis of more complex samples of E. coli cell lysates. Although overall site occupancy was low (<1%), some proteins contained lysines with relatively high acetylation occupancy.

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Measurement of sodium ion concentration in undiluted urine with cation-selective polymeric membrane electrodes after the removal of interfering compounds

The measurement of sodium ion concentration in urine can provide diagnostic information and guide therapy. Unfortunately, neutral-carrier-based ion-selective electrodes show a large positive drift and loss in selectivity in undiluted urine. The extraction of electrically neutral lipids from the urine into the sensing membrane was suggested as the main source of the drift, loss of selectivity and the consequent incorrect concentration readings.In this work, (i) solvent-solvent extraction, (ii) membrane-immobilized solvent extraction and (iii) solid phase extraction were used to remove interfering compounds from urine samples. The “cleaned” urine samples were subsequently analyzed using a calixarene (sodium ionophore X)-based, solid-contact, sodium-selective electrode in a flow-through manifold. The solid-contact sodium sensors had excellent stability in cleaned urine and an acceptable bias compared to commercial clinical analyzers.     

Large-scale synthesis of α-amino acid-N-carboxyanhydrides

Hetero- and homopolymers prepared from α-amino acid-N-carboxyanhydrides (NCAs) monomers are widely useful products. The preparation of pure NCA monomers has been extensively studied in the past. Purification methods including repeated crystallizations, extraction, and flash column chromatography have been devised. However, these methods are not easily amendable to large-scale NCA preparations. This article describes the synthesis of numerous highly purified NCAs on a >100?g scale using a simple filtration step through diatomaceous earth (celite). The resulting NCAs provided polyethylene glycol (PEG)–amino acid triblock polymers devoid of low-molecular-weight by-products that were routinely observed when unfiltered batches of NCAs were used. Also disclosed is the preparation of NCAs at ambient temperature. Traditionally, NCA reactions using a phosgene source are heated. This study shows these reactions can be driven by the slight exotherm that forms upon reagent mixing. This eliminates the need for an external heating source, simplifying large-scale reactions.     

Search for medium modifications of the rho meson

The photoproduction of vector mesons on various nuclei has been studied using the CLAS detector at Jefferson Laboratory. The vector mesons, rho, omega, and varphi, are observed via their decay to e;{+}e;{-}, in order to reduce the effects of final-state interactions in the nucleus. Of particular interest are possible in-medium effects on the properties of the rho meson. The rho mass spectrum is extracted from the data on various nuclei, 2H, C, Fe, and Ti. We observe no significant mass shift and some broadening consistent with expected collisional broadening for the rho meson.     

Optimal Prefix-Free Codes for Unequal Letter Costs: Dynamic Programming with the Monge Property

In this paper we discuss the problem of finding optimal prefix-free codes for unequal letter costs, a variation of the classical Huffman coding problem. Our problem consists of finding a minimal cost prefix-free code in which the encoding alphabet consists of unequal cost (length) letters, with lengths α and β. The most efficient algorithm known previously requires O(n^{2 + max(α, β)}) time to construct such a minimal-cost set of n codewords, provided α and β are integers. In this paper we provide an O(n^max(α, β)) time algorithm. Our improvement comes from the use of a more sophisticated modeling of the problem, combined with the observation that the problem possesses a “Monge property” and that the SMAWK algorithm on monotone matrices can therefore be applied.