A Novel Eigenvector-based Method to Detect Mild Alzheimer's Disease Using Event-Related Potentials.

Event-related potentials (ERPs) are a physiological measure of cognitive function that have shown diagnostic and prognostic utility in Alzheimer's disease (AD). In this study, we used a novel eigenvector-based technique to better understand brain electrophysiological differences between subjects with mild AD and healthy controls (HC). Using ERPs from 75 subjects with mild AD and 95 HC, we first calculated cognitive task eigenvectors within each subject from three conditions and then calculated second-order eigenvector components to compare the AD group to the HC group. A MANOVA of the three second-level components discriminated between AD and HC multivariately (Wilks' lambda=.4297, p<0.0001, R2 = .5703), and also on each of the three components univariately (all 3 p-values<0.0001). The eigenvector-based technique used in this study accurately discriminated between the mild AD group and HC. As such, this analysis method adds to our understanding of the differences in ERP signal between AD and HC, and could provide a sensitive biomarker for diagnosis and monitoring of AD progression.

Sidewall oxide effects on spin-torque- and magnetic-field-induced reversal characteristics of thin-film nanomagnets.

The successful operation of spin-based data storage devices depends on thermally stable magnetic bits. At the same time, the data-processing speeds required by today's technology necessitate ultrafast switching in storage devices. Achieving both thermal stability and fast switching requires controlling the effective damping in magnetic nanoparticles. By carrying out a surface chemical analysis, we show that through exposure to ambient oxygen during processing, a nanomagnet can develop an antiferromagnetic sidewall oxide layer that has detrimental effects, which include a reduction in the thermal stability at room temperature and anomalously high magnetic damping at low temperatures. The in situ deposition of a thin Al metal layer, oxidized to completion in air, greatly reduces or eliminates these problems. This implies that the effective damping and the thermal stability of a nanomagnet can be tuned, leading to a variety of potential applications in spintronic devices such as spin-torque oscillators and patterned media.

Effects of amorphous layers on ADF-STEM imaging.

A study of high-resolution ADF imaging in uncorrected and aberration-corrected STEMs was carried out by multislice simulation. The presence of amorphous layers at the surface of a crystalline specimen is shown to significantly alter the visibility of the atomic columns. After propagating through an amorphous layer a portion of the beam passes without any alteration while scattered electrons introduce a Gaussian background. The dependence of the image contrast on the crystal structure, orientation and the types of the atoms present in the crystal was studied. In the case of uncorrected probes an amorphous layer thicker than 200 A is necessary to achieve considerable reduction of the visibility of the atomic columns, but with aberration-corrected probes only 60 A is necessary. With changes in defocus, crystalline specimens with amorphous layers on the top can also be imaged and high-resolution ADF images can be obtained. An amorphous layer at the beam entry surface affects the ADF image more than that of an amorphous layer at the exit surface. Approximately linear reduction of the contrast (with a slop of 1) is expected with increased thickness of amorphous layer.

Critical role of inelastic interactions in quantitative electron microscopy.

A semiquantitative correlation between experimental observations and theoretical prediction in electron microscopy is achieved. Experiments conducted on amorphous silicon in the convergent beam electron diffraction mode provide measurements of the reduction of the central-disk intensity. In addition to elastic scattering the effects of multiple inelastic scattering of the probe electrons were incorporated into the theory describing beam propagation through the specimen. With incorporation of the dominant plasmon scattering a better than 10% match of the theory with experiment is observed indicating the critical role of multiple inelastic scattering in quantitative electron diffraction and imaging.

Atomic-scale chemical imaging of composition and bonding by aberration-corrected microscopy.

Using a fifth-order aberration-corrected scanning transmission electron microscope, which provides a factor of 100 increase in signal over an uncorrected instrument, we demonstrated two-dimensional elemental and valence-sensitive imaging at atomic resolution by means of electron energy-loss spectroscopy, with acquisition times of well under a minute (for a 4096-pixel image). Applying this method to the study of a La(0.7)Sr(0.3)MnO3/SrTiO3 multilayer, we found an asymmetry between the chemical intermixing on the manganese-titanium and lanthanum-strontium sublattices. The measured changes in the titanium bonding as the local environment changed allowed us to distinguish chemical interdiffusion from imaging artifacts.

Effects of specimen tilt in ADF-STEM imaging of a-Si/c-Si interfaces.

Annular dark field scanning transmission electron microscopy (ADF-STEM) imaging of a crystal depends strongly on specimen orientation, but for an amorphous sample it is insensitive to orientation changes. To fully investigate the effects of specimen tilt, an interface of amorphous Si (a-Si) and crystalline Si (c-Si) was rotated systematically off a zone axis in a STEM equipped with low-angle ADF (LAADF) and high-angle ADF (HAADF) detectors. The change of relative intensity across the interface shows very different trends in the LAADF and the HAADF images upon tilting. More importantly, it is found that the HAADF signal decreases much more rapidly when tilted off a zone axis than does the LAADF signal. The high-resolution lattice fringes also disappear much faster in the HAADF image than in the LAADF image. These trends reflect the fact that the channeling peaks that are responsible for scattering into the HAADF detector decrease more quickly upon tilting than the lower angle scattering to the LAADF detector does.

Effects of tilt on high-resolution ADF-STEM imaging.

A study of the effects of small-angle specimen tilt on high-resolution annular dark field images was carried out for scanning transmission electron microscopes with uncorrected and aberration-corrected probes using multislice simulations. The results indicate that even in the cases of specimen tilts of the order of 1 degree a factor of 2 reduction in the contrast of the high-resolution image should be expected. The effect holds for different orientations of the crystal. Calculations also indicate that as the tilted specimen gets thicker the contrast reduction increases. Images simulated with a low-angle annular dark field detector show that tilt effects are more pronounced in this case and suggest that these low-angle detectors can be used to correct specimen tilt during scanning transmission electron microscopes operation.

Separation of bulk and surface-losses in low-loss EELS measurements in STEM.

To identify major features in low electron energy loss spectra, the different excitations (bulk plasmons, interband transitions, surface plasmons, Cherenkov and surface guided modes) must be delineated from each other. In this paper, this process is achieved by noting the linear thickness dependence of bulk processes contrasted with the constant thickness behavior of surface excitations. An alternative approach of analyzing bulk plasmon-loss is also introduced. Using a new algorithm, the parameters of plasma generation-plasmon energy E(P,0), a damping parameter DeltaE(P) and the coefficient of the dispersion relation gamma were obtained from a single curve fitting on the example of Si. The ability to separate surface-losses from the rest of the data permitted identification of the fine structure of the surface-losses. The strong peak at 8.2 eV characteristic of non-radiative surface plasmon excitations was measured for Si. Analysis of surface excitations indicates that a 10ASiO2 surface coating layer is still present despite careful cleaning the specimen. Dielectric functions deduced from the EELS data prove to be considerably affected by the presence of the surface-losses for samples as thick as 800A.

Full recovery of electron damage in glass at ambient temperatures.

An unusually complete recovery of extensive electron-beam-induced damage in a thin film of a CaO-Al2O3-SiO2 glass was discovered. Nanoscale measurements show that the Ca ions migrate about 10 nm away during irradiation and return during recovery. Oxygen atoms are trapped largely as molecular oxygen and do not migrate. Electron energy loss measurements demonstrate that the glass returns completely to the original compositional and structural state thus indicating that the glass is in a deep thermodynamic energy minimum.

Direct determination of local lattice polarity in crystals.

With current advances in sub-angstrom resolution scanning transmission electron microscopy (STEM), it is now possible to image directly local crystal structures of materials where dramatically different atoms are separated from each other at distances about or less than 1 angstrom. We achieved direct imaging of atomic columns of nitrogen in close proximity to columns of aluminum in wurtzite aluminum nitride by using annular dark field imaging in an aberration-corrected STEM. This ability allows direct determination of the local polarity in nanoscale crystals and crystal defects.

Simulation of thermal diffuse scattering including a detailed phonon dispersion curve.

Thermal vibration of the atoms in a crystal give rise to a diffuse background in the diffraction pattern (in between the normal allowed Bragg reflections). The Einstein model for phonon vibrations in a crystal leads to Gaussian statistics for the phonons. However, the Einstein model ignores the possibility of correlation between the atoms. An accurate model of the phonon dispersion curves for silicon is used to generate a set of more accurate random atomic displacements. These displacements are used in a multislice-style simulation to gauge the validity of the Einstein approximation. The phonon dispersion curve yields a small additional oscillatory structure in the thermal diffuse scattering (TDS) pattern. This does not produce significant changes in the annular dark field scanning transmission electron microscope (ADF-STEM) image signal, but could have a large impact on convergent beam measurements of bond charges.

Annular dark-field image simulation of the YBa2Cu3O(7-delta)/BaF2 interface

Scanning transmission electron microscope (STEM) images of the interface of a YBa2Cu3O(7-delta) (YBCO)/BaF2 thin film bilayer show a relatively wide (approximately 40 A) contrasting band at the interface when viewed edge-on. Simulation of annular dark-field (ADF) images of this interface reveal that a significant contribution to this wide band of contrast is due to strain from dislocations oriented perpendicular to the incident beam direction and this contrast cannot be explained using solely a Z-contrast interpretation of ADF images. We believe that these are the first such calculations which predict that the presence of a misfit dislocation network can contribute a significant amount of contrast to cross-section ADF images of an interface.

Subnanometer-Diameter Wires Isolated in a Polymer Matrix by Fast Polymerization

The preparation and analysis of inorganic-organic polymer nanocomposites consisting of inorganic nanowires and multiwire "cables" in a random-coil organic polymer host is reported. Dissolution of inorganic (LiMo3Se3)n wires in a strongly coordinating monomer, vinylene carbonate, and the use of a rapid polymerization in the presence of a cross-linking agent produce nanocomposites without phase separation. Polymerization of dilute solutions yields a material containing mostly (Mo3Se3(-))n mono- and biwires, 6 to 20 angstroms in diameter and 50 to 100 nanometers long. Polymerization of more concentrated liquid crystalline solutions yields a nanocomposite containing oriented multiwire cables, 20 to 40 angstroms in diameter and up to 1500 nanometers long, that display optical anisotropy and electrical conductivity.

Transfer of carbetocin into human breast milk.

OBJECTIVE: To study the transfer of carbetocin into human breast milk. METHODS: Five healthy nursing women, 7-14 weeks postpartum, emptied their breasts using a breast pump and then received 70 micrograms carbetocin by intramuscular injection. Using a radioimmunoassay, the concentrations of carbetocin were measured in plasma and breast milk samples obtained before carbetocin administration and at 15, 30, 60, 90, 120, and 240 minutes after drug administration. RESULTS: For plasma, the mean (+/- standard deviation) area under the curve (AUC) of carbetocin versus time was 1119.3 +/- 315.9 pg/mL, a value about 50 times higher than the mean AUC for carbetocin in breast milk (18.6 +/- 13.7 and 29.0 +/- 23.8 pg/mL for the right and left breast, respectively). The ratio of milk to plasma AUC was low: 1.7 +/- 0.9 and 3.1 +/- 2.8% for the left and right breast, respectively. No serious adverse reactions occurred and no clinically significant changes in vital signs were found. CONCLUSION: Very little carbetocin is transferred into human breast milk, presenting little risk to breast-fed infants.

Cryoultramicrotomy: evidence against melting and the use of a low temperature cement for specimen orientation.

A technique is presented showing the use of toluene as a low temperature cement to attach portions of frozen tissues in the desired orientation on to the cryoultramicrotome chuck. Examples of transverse sections of skeletal and vascular smooth muscle are illustrated. Electron probe analysis of these sections indicates that the distribution of elements is maintained. Evidence is presented against through section melting based on sectioning toluene at a temperature just below its melting point (178K). Toluene was sectioned (about 100 nm thickness) successfully at three block temperatures (177, 163 and 113 K) when the knife temperature was by 1 degree or mor colder than the m.p. of toluene. In all cases the toluene sections melted when the knife temperature reached 178K. We conclude that sufficient heat is not generated and/or transferred to the toluene sections during cryosectioning under our conditions to raise the temperature of a 100 nm section by 1 K or more.