Oscillatory Tunneling between Quantum Hall Systems

Electron tunneling between quantum Hall systems on the same two dimensional plane separated by a narrow barrier is studied. We show that in the limit where inelastic scattering time is much longer than the tunneling time, which can be achieved in practice, electrons can tunnel back and forth through the barrier continously, leading to an oscillating current in the absence of external drives. The oscillatory behavior is dictated by a tunneling gap in the energy spectrum. We shall discuss ways to generate oscillating currents and the phenomenon of natural ``dephasing" between the tunneling currents of edge states. The noise spectra of these junctions are also studied. They contain singularites reflecting the existence of tunneling gaps as well as the inherent oscillation in the system. (Figures will be given upon requests).Comment: 20 pages, OS

Fine Mapping the Spatial Distribution and Concentration of Unlabeled Drugs within Tissue Micro-Compartments Using Imaging Mass Spectrometry

Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention

Interaction effects and phase relaxation in disordered systems

This paper is intended to demonstrate that there is no need to revise the existing theory of the transport properties of disordered conductors in the so-called weak localization regime. In particular, we demonstrate explicitly that recent attempts to justify theoretically that the dephasing rate (extracted from the magnetoresistance) remains finite at zero temperature are based on the profoundly incorrect calculation. This demonstration is based on a straightforward evaluation of the effect of the electron-electron interaction on the weak localization correction to the conductivity of disordered metals. Using well-controlled perturbation theory with the inverse conductance $g$ as the small parameter, we show that this effect consists of two contributions. First contribution comes from the processes with energy transfer smaller than the temperature. This contribution is responsible for setting the energy scale for the magnetoresistance. The second contribution originates from the virtual processes with energy transfer larger than the temperature. It is shown that the latter processes have nothing to do with the dephasing, but rather manifest the second order (in $1/g$) correction to the conductance. This correction is calculated for the first time. The paper also contains a brief review of the existing experiments on the dephasing of electrons in disordered conductors and an extended qualitative discussion of the quantum corrections to the conductivity and to the density of electronic states in the weak localization regime.Comment: 34 pages, 13 .eps figure

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation – time of flight – mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches

MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings

Imaging Mass Spectrometry: Hype or Hope?

Imaging mass spectrometry is currently receiving a significant amount of attention in the mass spectrometric community. It offers the potential of direct examination of biomolecular patterns from cells and tissue. This makes it a seemingly ideal tool for biomedical diagnostics and molecular histology. It is able to generate beautiful molecular images from a large variety of surfaces, ranging from cancer tissue sections to polished cross sections from old-master paintings. What are the parameters that define and control the implications, challenges, opportunities, and (im)possibilities associated with the application of imaging MS to biomedical tissue studies. Is this just another technological hype or does it really offer the hope to gain new insights in molecular processes in living tissue? In this critical insight this question is addressed through the discussion of a number of aspects of MS imaging technology and sample preparation that strongly determine the outcome of imaging MS experiments

Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry

Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues