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

Cloned Access Point Detection and Point Detection and Prevention Mechanism in IEEE 802.11 Wireless Mesh Networks

IEEE 802.11 Wireless Mesh Network (WMN) is an emerging low cost, decentralized community-based broadband technology, which is based on self-healing and multi-hop deployment of Access Points (APs), so that to increase the coverage area with maximum freedom to end-users to join or leave the network from anywhere anytime having low deployment and maintenance cost. Such kind of decentralized structure and multihop architecture increases its security vulnerabilities especially against the APs. One of such possible security attack is the placement of cloned AP to create serious performance degradation in IEEE 802.11 WMN. In this paper, we discuss the different security vulnerabilities of AP in IEEE 802.11 WMN along with possible research directions. We also propose a mutual cooperation mechanism between the multi-hop APs and serving gateway so that to detect and prevent the possibility of cloned AP. In this way the large scale exploitation of IEEE 802.11 WMN can be eliminated

Passive security threats and consequences in IEEE 802.11 wireless mesh networks

The Wireless Mesh Network (WMN) is ubiquitous emerging broadband wireless network. However, the open wireless medium, multi-hop multi-radio architecture and ad-hoc connectivity amongst end-users are such characteristics which increases the vulnerabilities of WMN towards many passive and active attacks. A secure network ensures the confidentiality, integrity and availability of wireless network. Integrity and availability is compromised by active attacks, while the confidentiality of end-users traffic is compromised by passive attacks. Passive attacks are silent in nature and do not harm the network traffic or normal network operations, therefore very difficult to detect. However, passive attacks lay down a foundation for later launching an active attack. In this article, we discuss the vulnerable features and possible passive threats in WMN along with current security mechanisms as well as future research directions. This article will serve as a baseline guide for the passive security threats and related issues in WMNs

Relative Price Volatility Under Sudden Stops: The Relevance of Balance Sheet Effects

Sudden Stops are associated with increased volatility in relative prices. We introduce a model based on information acquisition to rationalize this increased volatility. An empirical analysis of the conditional variance of the wholesale price to consumer price ratio using panel ARCH techniques confirms the relevance of Sudden Stops and potential balance-sheet effects as key determinants of relative-price volatility, where balance-sheet effects are captured by the interaction of a proxy for potential changes in the real exchange rate (linked to the degree of external leverage of the absorption of tradable goods) and a measure of domestic liability dollarization.

Strong coupling of magnons in a YIG sphere to photons in a planar superconducting resonator in the quantum limit

We report measurements of a superconducting coplanar waveguide resonator (CPWR) coupled to a sphere of yttrium-iron garnet. The non-uniform CPWR field allows us to excite various magnon modes in the sphere. Mode frequencies and relative coupling strengths are consistent with theory. Strong coupling is observed to several modes even with, on average, less than one excitation present in the CPWR. The time response to square pulses shows oscillations at the mode splitting frequency. These results indicate the feasibility of combining magnonic and planar superconducting quantum devices.Comment: 5 pages, 4 figure

Generation of density inhomogeneities by magnetohydrodynamic waves in two dimensions

Using two dimensional simulations, we study the formation of structures with a high-density contrast by magnetohydrodynamic waves in regions in which the ratio of thermal to magnetic pressure is small. The initial state is a uniform background perturbed by fast-mode wave. Our most significant result is that dense structures persist for far longer in a two-dimensional simulation than in the one-dimensional case. Once formed, these structures persist as long as the fast-mode amplitude remains high.Comment: 6 pages, 7 figures, accepted by MNRA

Skills Obsolescence: Causes and Cures

Until now there has been surprisingly little research on the causes of and the remedies for skills obsolescence. This study tries to fill that gap to some extent by analysing the relation between risk factors and skills obsolescence. Moreover, the role remedies play to counter skills obsolescence is analysed. Four empirical analyses that relate skills obsolescence to risk factors and remedies are presented. We find that most risk factors identified in the literature can be validated empirically. The remedies for skills obsolescence are not effective in all situations: the results show that there is considerable variation in the effectiveness of the remedies across different types of skills obsolescence. Although current available data does not allow a comprehensive analysis, which also takes account of relations between the various types of skills obsolescence, the results obtained are plausible and offer a starting point for further research.education, training and the labour market;