Addressing the needs of traumatic brain injury with clinical proteomics.

BackgroundNeurotrauma or injuries to the central nervous system (CNS) are a serious public health problem worldwide. Approximately 75% of all traumatic brain injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of concussion injury today is limited to an assessment of behavioral symptoms, often with delay and subject to motivation. Hence, there is an urgent need for an accurate chemical measure in biofluids to serve as a diagnostic tool for invisible brain wounds, to monitor severe patient trajectories, and to predict survival chances. Although a number of neurotrauma marker candidates have been reported, the broad spectrum of TBI limits the significance of small cohort studies. Specificity and sensitivity issues compound the development of a conclusive diagnostic assay, especially for concussion patients. Thus, the neurotrauma field currently has no diagnostic biofluid test in clinical use.ContentWe discuss the challenges of discovering new and validating identified neurotrauma marker candidates using proteomics-based strategies, including targeting, selection strategies and the application of mass spectrometry (MS) technologies and their potential impact to the neurotrauma field.SummaryMany studies use TBI marker candidates based on literature reports, yet progress in genomics and proteomics have started to provide neurotrauma protein profiles. Choosing meaningful marker candidates from such 'long lists' is still pending, as only few can be taken through the process of preclinical verification and large scale translational validation. Quantitative mass spectrometry targeting specific molecules rather than random sampling of the whole proteome, e.g., multiple reaction monitoring (MRM), offers an efficient and effective means to multiplex the measurement of several candidates in patient samples, thereby omitting the need for antibodies prior to clinical assay design. Sample preparation challenges specific to TBI are addressed. A tailored selection strategy combined with a multiplex screening approach is helping to arrive at diagnostically suitable candidates for clinical assay development. A surrogate marker test will be instrumental for critical decisions of TBI patient care and protection of concussion victims from repeated exposures that could result in lasting neurological deficits

An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes.

Mass spectrometry (MS) has become a crucial technique for the analysis of protein complexes. Native MS has traditionally examined protein subunit arrangements, while proteomics MS has focused on sequence identification. These two techniques are usually performed separately without taking advantage of the synergies between them. Here we describe the development of an integrated native MS and top-down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to analyse macromolecular protein complexes in a single experiment. We address previous concerns of employing FTICR MS to measure large macromolecular complexes by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the efficacy of this technique for direct acquirement of sequence to higher-order structural information with several large complexes. We then summarize the unique functionalities of different activation/dissociation techniques. The platform expands the ability of MS to integrate proteomics and structural biology to provide insights into protein structure, function and regulation

Low energy proton radiation damage to (AlGa)As-GaAs solar cells

Twenty-seven 2 times 2 sq cm (AlGa)As-GaAs solar cells were fabricated and subjected to 50 keV, 100 keV, and 290 keV of proton irradiation along with eighteen high efficiency silicon solar cells. The results of the study further corroborate the advantages for space missions offered by GaAs cells over state of the art silicon cells. Thus, even though the GaAs cells showed greater degradation when irradiated by protons with energy less than 5 MeV, the solar cells were normally protected from these protons by the glass covers used in space arrays. The GaAs cells also offered superior end of life power capability compared with silicon. The change in the open circuit voltage, short circuit current, spectral response, and dark 1-5 characteristics after irradiation at each proton energy and fluence were found to be consistent with the explanation of the effect of the protons. Also dark 1-5 characteristics showed that a new recombination center dominates the current transport mechanism after irradiation

Electron Radiation Damage of (alga) As-gaas Solar Cells

Solar cells (2 cm by 2 cm (AlGa) As-GaAs cells) were fabricated and then subjected to irradiation at normal incidence by electrons. The influence of junction depth and n-type buffer layer doping level on the cell's resistance to radiation damage was investigated. The study shows that (1) a 0.3 micrometer deep junction results in lower damage to the cells than does a 0.5 micrometer junction, and (2) lowering the n buffer layer doping density does not improve the radiation resistance of the cell. Rather, lowering the doping density decreases the solar cell's open circuit voltage. Some preliminary thermal annealing experiments in vacuum were performed on the (AlGa)As-GaAs solar cells damaged by 1-MeV electron irradiation. The results show that cell performance can be expected to partially recover at 200 C with more rapid and complete recovery occurring at higher temperature. For a 0.5hr anneal at 400 C, 90% of the initial power is recovered. The characteristics of the (AlGa)As-GaAs cells both before and after irradiation are described

A dynamic conductance model of fluorescent lamp for electronic ballast design simulation

A Spice-compatible dynamic conductance model of a fluorescent lamp for use in electronic ballast simulation is presented. The time-dependent conductance of the fluorescent lamp is derived from a plasma ionization balance equation that uses simplified descriptions of the physical processes within the lamp as its basis. The model has been designed to enable user-defined lamp radius, length, buffer gas pressure and cold-spot temperature as input parameters thus representing a valuable tool for ballast simulations. Simulation results are compared to experimental measurements and satisfactory agreement is achieved

Evaluation of diversity gains for DVB-T systems

Copyright @ 2008 Eurescom GmbHThe requirements for future DVB-T/H networks demand that broadcasters design and deploy networks that provide ubiquitous reception in challenging indoors and other obstructed situations. It is essential that such networks are designed costeffectively and with minimized environmental impact. The EC funded project PLUTO has since its start in 2006 explored the use of diversity to improve coverage in these difficult situations. The purpose of this paper is to investigate the performance of transmit and receive diversity gains with two antennas to improve the reception of DVB-T/H systems operating in different realistic propagation conditions through a series of tests using the Spirent dual channel emulator

The mechanisms of pedestrian slip on flooring contaminated with solid particles

Statistics by the UK Health and Safety Executive (HSE) suggest that slips, trips and falls account for up to one in three major workplace accidents. The vast majority of these accidents are the result of contaminant (fluid or solid) within the shoe-floor contact. Though the lubrication mechanisms for liquid contaminants within the contact are well understood, the same cannot be said for particulate contaminants. This paper considers the key parameters controlling friction in a shoe-floor contact contaminated with various particles of different diameters and shape factors and floors with different roughness values (Rz). Experiments were conducted using a Stanley Pendulum Tester, which is the floor friction tester recommended by the HSE. Results suggest that the adhesive friction is significantly affected by particulate contaminants, while the hysteretic component is not. Three lubrication mechanisms identified as sliding, shearing and rolling have been observed depending on floor roughness, particle size and shape factor and have been plotted in a simple map to predict behaviour

Medium energy proton radiation damage to (AlGa)As-GaAs solar cells

The performance of (AlGa)As-GaAs solar cells irradiated by medium energy 2, 5, and 10 MeV protons was evaluated. The Si cells without coverglass and a number of GaAs solar cells with 12 mil coverglass were irradiated simultaneously with bare GaAs cells. The cell degradation is directly related to the penetration of depth of protons with GaAs. The influence of periodic and continuous thermal annealing on the GaAs solar cells was investigated

GaAs solar cells for concentrator systems in space

Cells for operation in space up to more than 100 suns were made, and an AMO efficiency of 21% at 100 suns with these cells was obtained. The increased efficiency resulted not only from the higher open circuit voltage associated with the higher light intensity (higher short circuit current); it also benefitted from the increase in fill factor caused by the lower relative contribution of the generation recombination current to the forward bias current when the cell's operating current density is increased. The experimental cells exhibited an AMO efficiency close to 16% at 200 C. The prospect of exploiting this capability for the continuous annealing of radiation damage or for high temperature missions (e.g., near Sun missions) remains therefore open. Space systems with concentration ratios on the order of 100 suns are presently under development. The tradeoff between increased concentration ratio and increased loss due to the cell's series resistance remains attractive even for space applications at a solar concentrator ratio of 100 suns. In the design of contact configuration with low enough series resistance for such solar concentration ratios, the shallow junction depth needed for good radiation hardness and the thin AlGaAs layer thickness needed to avoid excessive optical absorption losses have to be retained