Expanding the Applications of Ion Mobility Spectrometry and Mass Spectrometry in Integrative \u27Omics Analyses

Over the past few decades, biomolecular analyses ranging from the study of complex mixtures to protein structural interrogation have increased significantly. These studies range from small molecule separations[1, 2] to observing structural trends in large proteins and protein sub-complexes.[3, 4] Traditionally, the use of liquid chromatography mass spectrometry (LC-MS), electrophoresis and nuclear magnetic resonance (NMR) spectroscopy have been at the forefront of these respective studies. Because complex mixtures can contain a variety of components over a wide dynamic range and proteins and their complexes can contain a diverse array of structures, few analytical techniques are capable of providing information across all experimental areas (e.g. small molecule mixtures to large individual proteins). In contrast, the use of Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS) has emerged as a powerful tool for measuring ion(s) structural heterogeneity. While IMS-MS is a relatively newer method, workflows are becoming more common as the commercialization of IMS instruments has created a larger user base. Such workflows now include metabolomic,[1, 5, 6] lipidomic,[7] proteomics and protein structural analyses[8, 9]. Taken collectively, these areas encompass the field of \u27omics\u27 analysis. While each field has its respective difficulties, IMS-MS is well poised to enhance and even expand the repertoire of analytical platforms for omics analyses.;Much of the current bottlenecks in traditional techniques suffer from an inability to sample measureable species rapidly in a reproducible manner over a wide dynamic range. For example, Anderson and coworkers have proposed that the plasma proteome includes 106--107 species that span a concentration range of 1011.[10] In many cases, IMS has shown improved resolution of isomeric species compared to either LC or Gas Chromatography (GC) analyses.[11, 12] The utility of IMS-MS in profiling is largely attributed to its rapid ability to resolve low-abundance species from spectral regions containing high-abundance species, thereby increasing measurement sensitivity, dynamic range and peak capacity.[13--17] Additionally, IMS is capable of separating isobaric species that cannot be resolved by MS alone. In \u27omic profiling directed toward biomarker discovery, it is imperative to identify compounds of interest. The identification is complicated by compound diversity (class and structural variation).;Traditionally, as well as all commercially available, IMS-MS instruments use Time-of-Flight (ToF) mass analyzers for determining an ion\u27s mass-to-charge ratio (m/z). The obvious advantage is the ability to nest the m/z measurement (micros) within the drift measurement (ms). This creates an orthogonal separation where many m/z measurements are made during the drift separation. Although this combination creates a rapid, multidimensional analysis, ToF mass analyzers are not capable of multistage tandem mass spectrometry (MSn) or nonergodic dissociation methods such as electron transfer dissociation (ETD). These MS fragmentation methods are often used as standalone techniques in applications ranging from small molecule identification within complex mixtures to identifying high order structure in proteins using Hydrogen Deuterium exchange (HDX) MS. To this end, new applications of IMS-MS that leverage the use of ion trapping MS are useful for supplementing these limitations of ToF analyzers. Trapping mass analyzers add the capability to perform ion-neutral or ion-ion reactions on drift-selected ions. In such experiments, fragment ions are generated and are structurally useful in identifying and quantifying individual components or those that compose protein structures or post translational modifications (PTMs). To date, very few, if any, experiments have attempted to combine the unique capabilities of IMS-MS with MSn or ETD-MS for uncovering ion structural information or heterogeneity. As will be shown in the coming chapters, coupling IMS to trapping mass analyzers expands the capabilities into new areas of \u27omics analysis and enhances the information that can be obtained from either technique alone

Dynamics of Vortex Core Switching in Ferromagnetic Nanodisks

Dynamics of magnetic vortex core switching in nanometer-scale permalloy disk, having a single vortex ground state, was investigated by micromagnetic modeling. When an in-plane magnetic field pulse with an appropriate strength and duration is applied to the vortex structure, additional two vortices, i.e., a circular- and an anti-vortex, are created near the original vortex core. Sequentially, the vortex-antivortex pair annihilates. A spin wave is created at the annihilation point and propagated through the entire element; the relaxed state for the system is the single vortex state with a switched vortex core.Comment: to appear in Appl. Phys. Let

An exploration of NHS clinical staff perceptions of changes to clinical products and their procurement

The NHS in England is working to reduce variation and waste in the use of clinical products, which requires collaboration between those directly involved in procurement and clinical staff. The procurement process is becoming centralised and standardised, and the involvement of, and consultation with, clinical staff is vital to avoid compromising patient care and safety. This article reports the results of a survey of clinical staff and clinical procurement specialist nurses undertaken as part of a master’s degree. Its aim was to capture staff experiences and perceptions of changes to clinical products

The measurement of lubricant-film thickness using ultrasound

Ultrasound is reflected from a liquid layer between two solid bodies. This reflection depends on the ultrasonic frequency, the acoustic properties of the liquid and solid, and the layer thickness. If the wavelength is much greater than the liquid-layer thickness, then the response is governed by the stiffness of the layer. If the wavelength and layer thickness are similar, then the interaction of ultrasound with the layer is controlled by its resonant behaviour. This stiffness governed response and resonant response can be used to determine the thickness of the liquid layer, if the other parameters are known. In this paper, ultrasound has been developed as a method to determine the thickness of lubricating films in bearing systems. An ultrasonic transducer is positioned on the outside of a bearing shell such that the wave is focused on the lubricant-film layer. The transducer is used to both emit and receive wide-band ultrasonic pulses. For a particular lubricant film, the reflected pulse is processed to give a reflection-coefficient spectrum. The lubricant-film thickness is then obtained from either the layer stiffness or the resonant frequency. The method has been validated using fluid wedges at ambient pressure between flat and curved surfaces. Experiments on the elastohydrodynamic film formed between a sliding ball and a flat surface were performed. Film-thickness values in the range 50-500 nm were recorded, which agreed well with theoretical film-formation predictions. Similar measurements have been made on the oil film between the balls and outer raceway of a deep-groove ball bearing

Evolution of Bars in Galaxies: Effects on Star Formation and Stellar Dynamics

The majority of disc galaxies have a bar, and bars play a major role in the evolution of galaxies and their properties. Given the cumulative influence that bars can have over the properties of their host, determining the epoch of their formation becomes a fundamental step in understanding disc galaxy evolution. However, this is not a straightforward task. The stars that make up the bar are not necessarily formed there and bars can radially move both gas and stars within a galaxy which makes determining a bar's age from the properties of its stellar population unreliable. Additionally, while bars grow as they age, this is not a linear process and bar growth progresses differently for different galaxies. In this thesis I have explored how the effects of bars on the star formation and stellar dynamics of galaxies can be used to recover the ages of bars using a sample of cosmological zoom-in re-simulations of galaxies in isolated environments. I first explored the effect of the bar on the star formation desert (SFD) in 6 of the isolated zoom-in cosmological re-simulations. The SFD is a region within the inner ring, lying either side of the bar in the area that the bar sweeps out. James and Percival (2016) found these regions had very little to no star formation and theorised that if star formation is suppressed by the bar the youngest stars in these regions should correspond to the age of the bar. I found that the removal of gas within the SFD occurs within 1-2 Gyr after the formation of the bar indicating there is little to no in-situ star formation after that time. We would, therefore, expect to see a sharp truncation in the star formation history. However, I found a gradual downturn in the star formation history of the SFD region in comparison to that of the bar, so all stars 1-2 Gyr younger than the bar must radially migrate into the SFD region. I propose that the onset of this downturn could still be used to recover the age of the bar, although the interpretation is more difficult than anticipated. However, I also present the discovery that the SFD is a region where any young stars must be radial migrators. By combining this with a bar age it would allow us to probe the timescales and efficiency of radial migration and thus gain unparalleled insight into the chemo-dynamical evolution of the SFD region. I also explored the effect of bars on galaxy stellar dynamics. As bars evolve they vertically thicken. Therefore, younger bars have a velocity dispersion similar to that of the disc while in older bars the difference is greater. I built on this by looking at features in the vertical velocity dispersion of the bar with a sample of 15 zoom-in cosmological re-simulations and 3 simulations of isolated galaxies. I uncovered a special feature in the vertical velocity dispersion of the bar. The location of this feature is remarkably stable with time and on average is 1.5 kpc shorter than the initial length of the bar. By taking the difference between the σ_z of this feature and the bar ends I calculated a value I call Δσ_z. I was able to recover Δσ_z in both cosmological and isolated simulations and found this value increases monotonically with the age of the bar at the same rate for all the bars in the sample. The growth of Δσ_z is influenced by two factors: the lengthening of the bar, and the vertical thickening of the bar. At early times after bar formation the lengthening of the bar is the main contributor to the increase seen in Δσ_z. However, after the bar buckles, the vertical thickening becomes the main contributor to the increase of Δσ_z. Therefore Δσ_z is a powerful tracer of bar growth as it is entirely constrained by the evolution of the bar. Thus I present a new bar dating method which uses Δσ_z to infer both the formation time of the bar and an estimate of the initial length of the bar. I have tested this new method on MUSE data of IC1438 and have found good agreement with literature data. This confirms that it is both possible to apply this method to current observational data and that the bar ages recovered are reasonable. This new method presents an exciting avenue for the reliable recovery of quantitative bar ages. By applying these methods and findings to large statistical surveys we can begin to explore the time of disc settling and the onset of secular processes. I conclude that this presents us with an exciting opportunity to explore how the formation of the bar can impact galaxy evolution

Pressure Tuning of the Charge Density Wave in the Halogen-Bridged Transition-Metal (MX) Solid Pt2Br6(NH3)4Pt_2Br_6(NH_3)_4

We report the pressure dependence up to 95 kbar of Raman active stretching modes in the quasi-one-dimensional MX chain solid $Pt_2Br_6(NH_3)_4$. The data indicate that a predicted pressure-induced insulator-to-metal transition does not occur, but are consistent with the solid undergoing either a three-dimensional structural distortion, or a transition from a charge-density wave to another broken-symmetry ground state. We show that such a transition cacan be well-modeled within a Peierls-Hubbard Hamiltonian. 1993 PACS: 71.30.+h, 71.45.Lr, 75.30.Fv, 78.30.-j, 81.40.VwComment: 4 pages, ReVTeX 3.0, figures available from the authors on request (Gary Kanner, [email protected]), to be published in Phys Rev B Rapid Commun, REVISION: minor typos corrected, LA-UR-94-246

In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development

Acknowledgments: The authors would like to acknowledge the funding support for this work from Scottish Enterprise [VNAR_001(2012)] and the Biotechnology and Biological Sciences Research Council (BB/K010905/1).Peer reviewedPublisher PD