607 research outputs found

    Geometry of Empty Space is the Key to Near-Arrest Dynamics

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    We study several examples of kinetically constrained lattice models using dynamically accessible volume as an order parameter. Thereby we identify two distinct regimes exhibiting dynamical slowing, with a sharp threshold between them. These regimes are identified both by a new response function in dynamically available volume, as well as directly in the dynamics. Results for the selfdiffusion constant in terms of the connected hole density are presented, and some evidence is given for scaling in the limit of dynamical arrest.Comment: 11 page

    Phase Behavior of DPPC in a DNA-Calcium-Zwitterionic Lipid Complex Studied by Small-Angle X-ray Scattering

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    In the presence of DNA and calcium, multilamellar liposomes of DPPC when in excess form complexes in which two distinct lamellar lipid phases coexist. The structure and phase behavior of both of these have been investigated using high-resolution small-angle X-ray scattering. The coexisting lipid phases exist within the same precipitated condensate with the phase behavior of the unbound lipid being affected by the complexed lipid phase. While the thermotropic phase transitions of the uncomplexed lipid from Lβ‘-Pβ‘-Lα occur as expected, the transitions of the bound lipid are substantially altered. This is manifested as an increase in the main transition temperature, Tm, of the bound lipid, which has been observed before (Tarahovsky, Y. S.; Khusainova, R. S.; Gorelov, A. V.; Nicolaeva, T. I.; Deev, A. A.; Dawson, K. A.; Ivanitsky, G. R. FEBS Lett. 1996, 390, 133. Kharakoz, D. P.; Khusainova, R. S.; Gorelov, A. V.; Dawson, K. A. FEBS Lett. 1999, 446, 27). However, we also observe an apparent disappearance of the ripple phase (Pβ‘) with increasing calcium concentration in the bound lipid phase. In addition we are in a position to comment on the mechanism of formation for complexes prepared in this way

    Insights into the In Vivo Regulation of Glutamate Dehydrogenase from the Foot Muscle of an Estivating Land Snail

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    Land snails, Otala lactea, survive in seasonally hot and dry environments by entering a state of aerobic torpor called estivation. During estivation, snails must prevent excessive dehydration and reorganize metabolic fuel use so as to endure prolonged periods without food. Glutamate dehydrogenase (GDH) was hypothesized to play a key role during estivation as it shuttles amino acid carbon skeletons into the Krebs cycle for energy production and is very important to urea biosynthesis (a key molecule used for water retention). Analysis of purified foot muscle GDH from control and estivating conditions revealed that estivated GDH was approximately 3-fold more active in catalyzing glutamate deamination as compared to control. This kinetic difference appears to be regulated by reversible protein phosphorylation, as indicated by ProQ Diamond phosphoprotein staining and incubations that stimulate endogenous protein kinases and phosphatases. The increased activity of the high-phosphate form of GDH seen in the estivating land snail foot muscle correlates well with the increased use of amino acids for energy and increased synthesis of urea for water retention during prolonged estivation

    Simultaneous release of a hydroxy-methylglutaryl coenzyme A reductase inhibitor and a glycoprotein IIb/IIIa antagonist from a thermoresponsive NiPAAm/NtBAAm copolymer system.

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    While deployment of intracoronary stents has been shown to reduce restenosis, stenting can also damage the endothelial was eluted during this period. Xemilofiban release was measured in terms of its ability to inhibit platelet adhesion, using a microfluidic system. To investigate the influence of location and hydrophobicity on elution of bioactivity, three separate systems were employed. While elution of anti-adhesive activity from the system containing xemilofiban-loaded matrices was more dramatic in the short term, a more sustained level of inhibition was achieved when xemilofiban had been incorporated into microgels. All samples investigated for anti-adhesive activity also decreased human coronary artery smooth muscle cell proliferation. Therefore xemilofiban has potential as an agent for preventing in-stent thrombosis. Our study has demonstrated the feasibility of using this novel matrix/microgel system to regulate simultaneous release of both agents in bioactive concentratio

    Clarification of the Bootstrap Percolation Paradox

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    We study the onset of the bootstrap percolation transition as a model of generalized dynamical arrest. We develop a new importance-sampling procedure in simulation, based on rare events around "holes", that enables us to access bootstrap lengths beyond those previously studied. By framing a new theory in terms of paths or processes that lead to emptying of the lattice we are able to develop systematic corrections to the existing theory, and compare them to simulations. Thereby, for the first time in the literature, it is possible to obtain credible comparisons between theory and simulation in the accessible density range.Comment: 4 pages with 3 figure

    A TEM protocol for quality assurance of in vitro cellular barrier models and its application to the assessment of nanoparticle transport mechanisms across barriers

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    A comprehensive transmission electron microscopy imaging protocol to characterisein vitrohuman cell barriers and study mechanisms of nanoparticle transport.</p

    Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles

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    Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily due to the absence of a microscopic picture of the surface presentation of the polymer. Here a detailed NMR analysis reveals three types of dynamic ethylene glycol units on PEG-grafted SiO2 nanoparticles (NPs) of the type commonly evaluated as long-circulating theranostic nano-probes; a narrow fraction with fast dynamics associated with the chain ends; a broadened fraction spectrally overlapped with the former arising from those parts of the chain experiencing some dynamic restriction; and a fraction too broad to be observed in the spectrum arising from units closer to the surface/graft which undergo slow motion on the NMR timescale. We demonstrate that ethylene glycol units transition between fractions as a function of temperature, core size, PEG chain length and surface coverage and demonstrate how this distribution affects colloidal stability and protein uptake. The implications of the findings for biological application of grafted nanoparticles are discussed in the context of accepted models for surface ligand conformation
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