Myelin and iron concentration in the human brain: a quantitative study of MRI contrast.

During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T1 mapping and T2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1µm spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples.

Silicide induced ion beam patterning of Si(001).

Low energy ion beam pattern formation on Si with simultaneous co-deposition of Ag, Pd, Pb, Ir, Fe or C impurities was investigated by in situ scanning tunneling microscopy as well as ex situ atomic force microscopy, scanning electron microscopy, transmission electron microscopy and Rutherford backscattering spectrometry. The impurities were supplied by sputter deposition. Additional insight into the mechanism of pattern formation was obtained by more controlled supply through e-beam evaporation. For the situations investigated, the ability of the impurity to react with Si, i.e. to form a silicide, appears to be a necessary, but not a sufficient condition for pattern formation. Comparing the effects of impurities with similar mass and nuclear charge, the collision kinetics is shown to be not of primary importance for pattern formation. To understand the observed phenomena, it is necessary to assume a bi-directional coupling of composition and height fluctuations. This coupling gives rise to a sensitive dependence of the final morphology on the conditions of impurity supply. Because of this history dependence, the final morphology cannot be uniquely characterized by a steady state impurity concentration.

Deterministic Shallow Dopant Implantation in Silicon with Detection Confidence Upper-Bound to 99.85% by Ion-Solid Interactions.

Silicon chips containing arrays of single dopant atoms can be the material of choice for classical and quantum devices that exploit single donor spins. For example, group-V donors implanted in isotopically purified 28 Si crystals are attractive for large-scale quantum computers. Useful attributes include long nuclear and electron spin lifetimes of 31 P, hyperfine clock transitions in 209 Bi or electrically controllable 123 Sb nuclear spins. Promising architectures require the ability to fabricate arrays of individual near-surface dopant atoms with high yield. Here, an on-chip detector electrode system with 70 eV root-mean-square noise (≈20 electrons) is employed to demonstrate near-room-temperature implantation of single 14 keV 31 P+ ions. The physics model for the ion-solid interaction shows an unprecedented upper-bound single-ion-detection confidence of 99.85 ± 0.02% for near-surface implants. As a result, the practical controlled silicon doping yield is limited by materials engineering factors including surface gate oxides in which detected ions may stop. For a device with 6 nm gate oxide and 14 keV 31 P+ implants, a yield limit of 98.1% is demonstrated. Thinner gate oxides allow this limit to converge to the upper-bound. Deterministic single-ion implantation can therefore be a viable materials engineering strategy for scalable dopant architectures in silicon devices.

Detection of small bunches of ions using image charges.

A concept for detection of charged particles in a single fly-by, e.g. within an ion optical system for deterministic implantation, is presented. It is based on recording the image charge signal of ions moving through a detector, comprising a set of cylindrical electrodes. This work describes theoretical and practical aspects of image charge detection (ICD) and detector design and its application in the context of real time ion detection. It is shown how false positive detections are excluded reliably, although the signal-to-noise ratio is far too low for time-domain analysis. This is achieved by applying a signal threshold detection scheme in the frequency domain, which - complemented by the development of specialised low-noise preamplifier electronics - will be the key to developing single ion image charge detection for deterministic implantation.

Zinc- and iron-dependent cytosolic metallo-beta-lactamase domain proteins exhibit similar zinc-binding affinities, independent of an atypical glutamate at the metal-binding site.

ZiPD (zinc phosphodiesterase; synonyms are ElaC, ecoZ, RNaseZ and 3' tRNase) and the iron-dependent redox enzyme FlRd (flavorubredoxin) from Escherichia coli represent prototypical cases of proteins sharing the metallo-beta-lactamase fold that require strict metal selectivity for catalytic activity, yet their metal selectivity has only been partially understood. In contrast with hydrolytic metallo-beta-lactamase proteins, iron-dependent FlRd-like enzymes have an atypical glutamate ligand, which replaces one otherwise conserved histidine ligand. X-ray absorption spectroscopy revealed that the FlRd metallo-beta-lactamase domain is capable of incorporating two zinc ions into the binuclear metal-binding site. Zinc dissociation constants, determined by isothermal titration calorimetry are similar for zinc binding to E. coli ZiPD (K(d1)=2.2+/-0.2 microM and K(d2)=23.0+/-0.6 microM) and to the E. coli FlRd metallo-beta-lactamase domain (K(d1)=0.7+/-0.1 microM and K(d2)=26.0+/-0.1 microM). In good correspondence, apo-ZiPD requires incubation with 10 microM zinc for full reconstitution of the phosphodiesterase activity. Accordingly, metal selectivity of ZiPD and FlRd only partially relies on first shell metal ligands. Back mutation of the atypical glutamate in FlRd to a histidine unexpectedly resulted in an increased first zinc dissociation constant (K(d1)=30+/-4 microM and K(d2)=23+/-2 microM). In combination with a recent mutational study on ZiPD [Vogel, Schilling and Meyer-Klaucke (2004) Biochemistry 43, 10379-10386], we conclude that the atypical glutamate does not guide metal selectivity of the FlRd metallo-beta-lactamase domain but suppresses possible hydrolytic cross-activity.

(55)Mn pulsed ENDOR spectroscopy of Mn(2+) ions in ZnO thin films and single crystal.

(55)Mn pulsed electron nuclear double resonance (ENDOR) experiments were performed at X-band on high spin S=5/2 Mn(2+) ions incorporated at zinc lattice sites in heteroepitaxial ZnO thin films. The films have been prepared by pulsed laser deposition and the manganese ions were doped during the growth process. We examine how the c/a lattice axes ratio of the ZnO films influences the (55)Mn hyperfine (hf) and nuclear quadrupole (nq) coupling parameters of the Mn(2+) probe ions. The results are compared with those obtained for Mn(2+) ions present as impurities in ZnO single crystals and revealed that the (55)Mn nq coupling monitors sensitively the structural distortions in the bonding environment of the Mn(2+) ions. The experiments provided the full axially symmetric (55)Mn hf and nq interaction tensors. The latter is found to be very sensitive to small axial distortions of the MnO4 tetrahedrons. In particular, the (55)Mn pulsed ENDOR spectra of the ZnO:Mn thin films are strongly subjected to strain effects in the nq coupling parameter indicating a variation of the local structural parameters for the heteroepitaxial films. In the analysis of the (55)Mn pulsed ENDOR spectra the axial and cubic zero field splitting of the Mn(2+) ions was taken into account and intensity effects in the ENDOR spectra due to the zero field splitting effects were discussed.

A quantitative study of the intracellular concentration of graphene/noble metal nanoparticle composites and their cytotoxicity.

Noble-metal nanoparticles (NPs) especially prepared from gold and silver have been combined on the surface of graphene to obtain graphene-based nanocomposites for novel functions in enhanced performance in bio-imaging, cancer detection and therapy. However, little is known about their cellular uptake, especially the intracellular quantity which plays a critical role in determining their functions and safety. Therefore, we prepared covalently conjugated GO/Au and GO/Ag composites by immobilizing Au and Ag nanoparticles on GO sheets pre-functionalized with disulfide bonds, respectively. The cellular uptake of these composites was quantitatively studied by means of an ion beam microscope (IBM) to determine the metal content in human lung cancer cells (A549 cells) and liver hepatocellular carcinoma cells (HepG2 cells). The cell uptake was also studied by inductively coupled plasma mass spectrometry (ICP-MS), which is one of the most sensitive techniques being applied to cell suspensions, for comparison. Toxicity, one of the consequences of cellular uptake of GO based composites, was studied as well. The potential toxicity mechanism was also suggested based on the results of intracellular quantification of the nanomaterials.