Dynamical and quasistatic structural relaxation paths in Pd_(40)Ni_(40)P_(20) glass

By sequential heat treatment of a Pd_(40)Ni_(40)P_(20) metallic glass at temperatures and durations for which α-relaxation is not possible, dynamic, and quasistatic relaxation paths below the glass transition are identified via ex situ ultrasonic measurements following each heat treatment. The dynamic relaxation paths are associated with hopping between nonequilibrium potential energy states of the glass, while the quasistatic relaxation path is associated with reversible β-relaxation events toward quasiequilibrium states. These quasiequilibrium states are identified with secondary potential energy minima that exist within the inherent energy minimum of the glass, thereby supporting the concept of the sub-basin/metabasin organization of the potential-energy landscape

Inhibition of Neutral Amino Acid Transport Across the Human Blood-Brain Barrier by Phenylalanine

The delivery of large neutral amino acids (LNAAs) to brain across the blood-brain barrier (BBB) is mediated by the L-type neutral amino acid transporter present in the membranes of the brain capillary endothelial cell. In experimental animals, the L-system transporter is saturated under normal conditions, and therefore an elevation in the plasma concentration of one LNAA will reduce brain uptake of others. In this study, we used positron emission tomography (PET) to determine the effect of elevated plasma phenylalanine concentrations on the uptake of an artificial neutral amino acid, [ 11 C]-aminocyclohexanecarboxylate ([ 11 C]ACHC), in human brain. PET scans were performed on six normal male subjects after an overnight fast and again 60 min after oral administration of 100 mg/kg of phenylalanine. The plasma phenylalanine concentration increased by an average of 11-fold between the first and second scans. This increase produced a reduction in [ 11 C]ACHC uptake in all brain regions but not in scalp. The mean ± SD influx rate constant for whole brain decreased after phenylalanine ingestion from 0.036 ± 0.002 to 0.019 ± 0.004 ml/g/min. Kinetic analysis of the effect of plasma phenylalanine concentration on the rate of [ 11 C]ACHC uptake is compatible with a model of competitive inhibition so that large increases in the concentration of one LNAA in plasma will reduce the brain uptake of other LNAAs across the human BBB.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65880/1/j.1471-4159.1995.64031252.x.pd

Conformation of the Transmembrane Domain of the Anthrax Toxin Receptor

Restauració dels vitrallsFoto final, plafó a6, cara interna, amb llum a través. Geomètric

Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function

The hydrophobic coupling between membrane-spanning proteins and the lipid bilayer core causes the bilayer thickness to vary locally as proteins and other “defects” are embedded in the bilayer. These bilayer deformations incur an energetic cost that, in principle, could couple membrane proteins to each other, causing them to associate in the plane of the membrane and thereby coupling them functionally. We demonstrate the existence of such bilayer-mediated coupling at the single-molecule level using single-barreled as well as double-barreled gramicidin channels in which two gramicidin subunits are covalently linked by a water-soluble, flexible linker. When a covalently attached pair of gramicidin subunits associates with a second attached pair to form a double-barreled channel, the lifetime of both channels in the assembly increases from hundreds of milliseconds to a hundred seconds—and the conductance of each channel in the side-by-side pair is almost 10% higher than the conductance of the corresponding single-barreled channels. The double-barreled channels are stabilized some 100,000-fold relative to their single-barreled counterparts. This stabilization arises from: first, the local increase in monomer concentration around a single-barreled channel formed by two covalently linked gramicidins, which increases the rate of double-barreled channel formation; and second, from the increased lifetime of the double-barreled channels. The latter result suggests that the two barrels of the construct associate laterally. The underlying cause for this lateral association most likely is the bilayer deformation energy associated with channel formation. More generally, the results suggest that the mechanical properties of the host bilayer may cause the kinetics of membrane protein conformational transitions to depend on the conformational states of the neighboring proteins

Microscopic Model for Granular Stratification and Segregation

We study segregation and stratification of mixtures of grains differing in size, shape and material properties poured in two-dimensional silos using a microscopic lattice model for surface flows of grains. The model incorporates the dissipation of energy in collisions between rolling and static grains and an energy barrier describing the geometrical asperities of the grains. We study the phase diagram of the different morphologies predicted by the model as a function of the two parameters. We find regions of segregation and stratification, in agreement with experimental finding, as well as a region of total mixing.Comment: 4 pages, 7 figures, http://polymer.bu.edu/~hmakse/Home.htm

Assessment of the biodistribution of an [ 18 F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97497/1/cmmi1532.pd

Regional vesicular acetylcholine transporter distribution in human brain: A [18F]fluoroethoxybenzovesamicol positron emission tomography study

Prior efforts to image cholinergic projections in human brain in vivo had significant technical limitations. We used the vesicular acetylcholine transporter (VAChT) ligand [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) and positron emission tomography to determine the regional distribution of VAChT binding sites in normal human brain. We studied 29 subjects (mean age 47 [range 20–81] years; 18 men; 11 women). [18F]FEOBV binding was highest in striatum, intermediate in the amygdala, hippocampal formation, thalamus, rostral brainstem, some cerebellar regions, and lower in other regions. Neocortical [18F]FEOBV binding was inhomogeneous with relatively high binding in insula, BA24, BA25, BA27, BA28, BA34, BA35, pericentral cortex, and lowest in BA17–19. Thalamic [18F]FEOBV binding was inhomogeneous with greatest binding in the lateral geniculate nuclei and relatively high binding in medial and posterior thalamus. Cerebellar cortical [18F]FEOBV binding was high in vermis and flocculus, and lower in the lateral cortices. Brainstem [18F]FEOBV binding was most prominent at the mesopontine junction, likely associated with the pedunculopontine–laterodorsal tegmental complex. Significant [18F]FEOBV binding was present throughout the brainstem. Some regions, including the striatum, primary sensorimotor cortex, and anterior cingulate cortex exhibited age‐related decreases in [18F]FEOBV binding. These results are consistent with prior studies of cholinergic projections in other species and prior postmortem human studies. There is a distinctive pattern of human neocortical VChAT expression. The patterns of thalamic and cerebellar cortical cholinergic terminal distribution are likely unique to humans. Normal aging is associated with regionally specific reductions in [18F]FEOBV binding in some cortical regions and the striatum.Using [18F]FEOBV PET, we describe the distribution of cholinergic terminals in human brain. The distribution of cholinergic terminals is similar to that found in other mammals with some distinctive features in cortex, thalamus, and cerebellum. There are regionally specific age‐related changes in cholinergic terminal density.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146604/1/cne24541.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146604/2/cne24541_am.pd

Piii‐37

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109838/1/cptclpt2006257.pd