Improvement of Capture Compound Mass Spectrometry Technology (CCMS) for the Profiling of Human Kinases by Combination with 2D LC-MS/MS

An increasingly popular and promising field in functional proteomics is the isolation of proteome subsets based on small molecule-protein interactions. One platform approach in this field are Capture Compounds that contain a small molecule of interest to bind target proteins, a photo-activatable reactivity function to covalently trap bound proteins, and a sorting function to isolate captured protein conjugates from complex biological samples for direct protein identification by liquid chromatography/mass spectrometry (nLC-MS/MS). In this study we used staurosporine as a selectivity group for analysis in HepG2 cells derived from human liver. In the present study, we combined the functional isolation of kinases with different separation workflows of automated split-free nanoflow liquid chromatography prior to mass spectrometric analysis. Two different CCMS setups, CCMS technology combined with 1D LC-MS and 2D LC-MS, were compared regarding the total number of kinase identifications. By extending the chromatographic separation of the tryptic digested captured proteins from 1D LC linear gradients to 2D LC we were able to identify 97 kinases. This result is similar to the 1D LC setup we previously reported but this time 4 times less input material was needed. This makes CCMS of kinases an even more powerful tool for the proteomic profiling of this important protein family

Gap Anisotropy and de Haas-van Alphen Effect in Type-II Superconductors

We present a theoretical study on the de Haas-van Alphen (dHvA) oscillation in the vortex state of type-II superconductors, with a special focus on the connection between the gap anisotropy and the oscillation damping. Numerical calculations for three different gap structures clearly indicate that the average gap along extremal orbits is relevant for the magnitude of the extra damping, thereby providing a support for experimental efforts to probe gap anisotropy through the dHvA signal. We also derive an analytic formula for the extra damping which gives a good fit to the numerical results.Comment: 5 pages, 1 figure, changes in Introductio

Phase sensitive absolute amplitude detection of surface vibrations using homodyne interferometry without active stabilization

A detection scheme for obtaining phase and absolute amplitude information of surface vibrations on microacoustic components using homodyne laser interferometry is described. The scheme does not require active stabilization of the optical path length of the interferometer. The detection setup is realized in a homodyneMichelson interferometer configuration, and selected measurements on a 374 MHz surface acoustic wave fan-shaped filter and two different piezoelectrically actuated micromechanical resonators are presented to demonstrate the performance of the instrument. With the current detection electronics, the interferometer is capable of detecting out-of-plane surface vibrations up to 2 GHz with a lateral resolution of better than 1 μm and with a minimum detectable vibration amplitude of ∼1 pm.Peer reviewe

Characterization of energy trapping in a bulk acoustic wave resonator

Acoustic wave fields both within the active electrode area of a solidly mounted 1.8 GHz bulk acoustic waveresonator, and around it in the surrounding region, are measured using a heterodyne laser interferometer. Plate-wave dispersion diagrams for both regions are extracted from the measurement data. The experimental dispersion data reveal the cutoff frequencies of the acoustic vibration modes in the region surrounding the resonator, and, therefore, the energy trapping range of the resonator can readily be determined. The measureddispersionproperties of the surrounding region, together with the abruptly diminishing amplitude of the dispersion curves in the resonator, signal the onset of acoustic leakage from the resonator. This information is important for verifying and further developing the simulation tools used for the design of the resonators. Experimental wave field images, dispersion diagrams for both regions, and the threshold for energy leakage are discussed.Peer reviewe

Evidence for a Second Order Phase Transition in Glasses at Very Low Temperatures -- A Macroscopic Quantum State of Tunneling Systems

Dielectric measurements at very low temperature indicate that in a glass with the eutectic composition BaO-Al$_2$O$_3$-SiO$_2$ a phase transition occurs at 5.84 mK. Below that temperature small magnetic fields of the order of 10 $\mu$T cause noticeable changes of the dielectric constant although the glass is insensitive to fields up to 20 T above 10 mK. The experimental findings may be interpreted as the signature of the formation of a new phase in which many tunneling systems perform a coherent motion resulting in a macroscopic wave function.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Quasiparticle Density of States of Clean and Dirty s-Wave Superconductors in the Vortex State

The quasiparticle density of states (DOS) in the vortex state has been probed by specific heat measurements under magnetic fields (H) for clean and dirty s-wave superconductors, Y(Ni1-xPtx)2B2C and Nb1-xTaxSe2. We find that the quasiparticle DOS per vortex is appreciably H-dependent in the clean-limit superconductors, while it is H-independent in the dirty superconductors as expected from a conventional rigid normal electron core picture. We discuss possible origins for our observations in terms of the shrinking of the vortex core radius with increasing H.Comment: 5 pages, 4 figures, to appear in J. Phys. Soc. Jpn. Vol. 68 No.

Extraction of lateral eigenmode properties in thin film bulk acoustic wave resonator from interferometric measurements

A heterodyne laser interferometer is used to study acoustic wave fields excited in a 1.8 GHz AlN thin film bulk acoustic waveresonator. The electrical response of the resonator exhibits a strong thickness resonance onto which spurious modes, caused by lateral standing plate waves, are superposed. Optical interferometermeasurements are used to extract dispersion curves of the laterally propagating waves responsible for the spurious responses. A discrete eigenmode spectrum due to the finite lateral dimensions of the resonator is observed. An equivalent circuit model for a multimode resonator is fitted to the mechanical resonator response extracted along a single curve in the dispersion diagram, and is used to determine properties, such as Q-values, of the individual lateral eigenmodes.Measuredwave field images, extracted dispersion curves, and the eigenmode spectrum with the model fitting results are presented.Peer reviewe

Evaluation of a Diagnostic Reasoning Program (DxR): Exploring Student Perceptions and Addressing Faculty Concerns

Abstract: Clinical reasoning is essentially a problem-solving process, in which medical students must learn to gather and interpret data, generate hypotheses and make decisions. To develop skills in problem-solving it is argued that students need more tools, rather than more answers (Masys, 1989). DxR is a computerised case series, in which students use 'doctor tools' to investigate a patient problem. This report describes a pilot evaluation of DxR in fourth year medicine at the University of Sydney. It addresses faculty concerns regarding the program, explores student perceptions, and looks at the capacity of the program to stimulate and support the development of clinical reasoning skills. It finally discusses possibilities for using DxR to support learning in medicine. Reviewers: Stig Andersen (Virtual Centre for Health Informatics, Aalborg, DK), David Good (U. Cambridge), Timothy Koschmann (U. Colorado) Interactive elements: 'Details are provided for obtaining a DxR demonstration CD.' DxR is distributed by NOVARTIS, although the DxR cases described in this article are not the same as those listed in the Diagnosis category of their bookshop/website. A Macromedia Director demonstration of DxR can be obtained by contacting Tanaya Patel, Project Director, DxR Development Group ([email protected]). Alternatively, a demonstration CD, and complimentary catalogue of patient cases and price list can be obtained by calling 800-631-1181 (USA)