Connectivity Mapping for Candidate Therapeutics Identification Using Next Generation Sequencing RNA-Seq Data

The advent of next generation sequencing technologies (NGS) has expanded the area of genomic research, offering high coverage and increased sensitivity over older microarray platforms. Although the current cost of next generation sequencing is still exceeding that of microarray approaches, the rapid advances in NGS will likely make it the platform of choice for future research in differential gene expression. Connectivity mapping is a procedure for examining the connections among diseases, genes and drugs by differential gene expression initially based on microarray technology, with which a large collection of compound-induced reference gene expression profiles have been accumulated. In this work, we aim to test the feasibility of incorporating NGS RNA-Seq data into the current connectivity mapping framework by utilizing the microarray based reference profiles and the construction of a differentially expressed gene signature from a NGS dataset. This would allow for the establishment of connections between the NGS gene signature and those microarray reference profiles, alleviating the associated incurring cost of re-creating drug profiles with NGS technology. We examined the connectivity mapping approach on a publicly available NGS dataset with androgen stimulation of LNCaP cells in order to extract candidate compounds that could inhibit the proliferative phenotype of LNCaP cells and to elucidate their potential in a laboratory setting. In addition, we also analyzed an independent microarray dataset of similar experimental settings. We found a high level of concordance between the top compounds identified using the gene signatures from the two datasets. The nicotine derivative cotinine was returned as the top candidate among the overlapping compounds with potential to suppress this proliferative phenotype. Subsequent lab experiments validated this connectivity mapping hit, showing that cotinine inhibits cell proliferation in an androgen dependent manner. Thus the results in this study suggest a promising prospect of integrating NGS data with connectivity mapping. © 2013 McArt et al.

Physical characterisation and component release of poly(vinyl alcohol)-tetrahydroxyborate hydrogels and their applicability as potential topical drug delivery systems

Poly(vinyl alcohol)-tetrahydroxyborate (PVA-THB) hydrogels are dilatant formulations with potential for topical wound management. To support this contention, the physical properties, rheological behaviour and component release of candidate formulations were investigated. Oscillatory rheometry and texture profile analysis were used at room temperature and 37 °C. Results showed that it was possible to control the rheological and textural properties by altering component concentration and modifying the type of PVA polymer used. Hydrogels made using PVA grades with higher degrees of hydrolysis displayed favourable characteristics from a wound healing perspective. In vitro release of borate and PVA were assessed in order to evaluate potential clinical dosing of free species originating from the hydrogel structure. Component diffusion was influenced by both concentration and molecular weight, where relevant, with up to 5% free PVA cumulative release observed after 30 min. The results of this study demonstrated the importance of poly(vinyl alcohol) selection for ensuring appropriate gel formation in PVA-THB hydrogels. The benefits of higher degrees of hydrolysis, in particular, included lower excipient release and reduced bioadhesion. The unique physical characteristics of these hydrogels make them an appealing delivery vehicle for chronic and acute wound management purposes.

Analog of Rabi oscillations in resonant electron-ion systems

Quantum coherence between electron and ion dynamics, observed in organic semiconductors by means of ultrafast spectroscopy, is the object of recent theoretical and computational studies. To simulate this kind of quantum coherent dynamics, we have introduced in a previous article [L. Stella, M. Meister, A. J. Fisher, and A. P. Horsfield, J. Chem. Phys. 127, 214104 (2007)] an improved computational scheme based on Correlated Electron-Ion Dynamics (CEID). In this article, we provide a generalization of that scheme to model several ionic degrees of freedom and many-body electronic states. To illustrate the capability of this extended CEID, we study a model system which displays the electron-ion analog of the Rabi oscillations. Finally, we discuss convergence and scaling properties of the extended CEID along with its applicability to more realistic problems. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3589165]

Transmit and receive filter design for OFDM based WLAN systems

We analyze the effect of different pulse shaping filters on the orthogonal frequency division multiplexing (OFDM) based wireless local area network (LAN) systems in this paper. In particular, the performances of the square root raised cosine (RRC) pulses with different rolloff factors are evaluated and compared. This work provides some guidances on how to choose RRC pulses in practical WLAN systems, e.g., the selection of rolloff factor, truncation length, oversampling rate, quantization levels, etc.

Analysis of Temporal Compression Characteristics using Active Phase conjugation in systems with multiple antenna elements

In this paper we give first account of a simple analysis tool for modeling temporal compression for automatic mitigation of multipath induced intersymbol interference through the use of active phase conjugation (APC) technique. The temporal compression characteristics of an APC system is analyzed using a simple discrete channel model, and numerical results are provided to justify the theoretical findings.

Circular Polarization Modulation for Digital Communication Systems

Conventional approaches of digital modulation schemes make use of amplitude, frequency and/or phase as modulation characteristic to transmit data. In this paper, we exploit circular polarization (CP) of the propagating electromagnetic carrier as modulation attribute which is a novel concept in digital communications. The requirement of antenna alignment to maximize received power is eliminated for CP signals and these are not affected by linearly polarized jamming signals. The work presents the concept of Circular Polarization Modulation for 2, 4 and 8 states of carrier and refers them as binary circular polarization modulation (BCPM), quaternary circular polarization modulation (QCPM) and 8-state circular polarization modulation (8CPM) respectively. Issues of modulation, demodulation, 3D symbol constellations and 3D propagating waveforms for the proposed modulation schemes are presented and analyzed in the presence of channel effects, and they are shown to have the same bit error performance in the presence of AWGN compared with conventional schemes while provide 3dB gain in the flat Rayleigh fading channel.

An extended framework for evidential reasoning systems

Based on the Dempster-Shafer (D-S) theory of evidence and G. Yen's (1989), extension of the theory, the authors propose approaches to representing heuristic knowledge by evidential mapping and pooling the mass distribution in a complex frame by partitioning that frame using Shafter's partition technique. The authors have generalized Yen's model from Bayesian probability theory to the D-S theory of evidence. Based on such a generalized model, an extended framework for evidential reasoning systems is briefly specified in which a semi-graph method is used to describe the heuristic knowledge. The advantage of such a method is that it can avoid the complexity of graphs without losing the explicitness of graphs. The extended framework can be widely used to build expert systems

Entanglement control in hybrid optomechanical systems

We demonstrate the control of entanglement in a hybrid optomechanical system comprising an optical cavity with a mechanical end-mirror and an intracavity Bose-Einstein condensate. Pulsed laser light (tuned within realistic experimental conditions) is shown to induce an almost sixfold increase of the atom-mirror entanglement and to be responsible for interesting dynamics between such mesoscopic systems. In order to assess the advantages offered by the proposed control technique, we compare the time-dependent dynamics of the system under constant pumping with the evolution due to the modulated laser light.

Evaluation of a substructured soft Real-time Hybrid Test for performing Seismic analysis of complex structural systems

The hybrid test method is a relatively recently developed dynamic testing technique that uses numerical modelling combined with simultaneous physical testing. The concept of substructuring allows the critical or highly nonlinear part of the structure that is difficult to numerically model with accuracy to be physically tested whilst the remainder of the structure, that has a more predictable response, is numerically modelled. In this paper, a substructured soft-real time hybrid test is evaluated as an accurate means of performing seismic tests of complex structures. The structure analysed is a three-storey, two-by-one bay concentrically braced frame (CBF) steel structure subjected to seismic excitation. A ground storey braced frame substructure whose response is critical to the overall response of the structure is tested, whilst the remainder of the structure is numerically modelled. OpenSees is used for numerical modelling and OpenFresco is used for the communication between the test equipment and numerical model. A novel approach using OpenFresco to define the complex numerical substructure of an X-braced frame within a hybrid test is also presented. The results of the hybrid tests are compared to purely numerical models using OpenSees and a simulated test using a combination of OpenSees and OpenFresco. The comparative results indicate that the test method provides an accurate and cost effective procedure for performing
full scale seismic tests of complex structural systems.

Understanding how HR systems work: the role of HR philosophy and HR processes

Despite the proliferation of studies of HR systems, there are still substantial gaps in our understanding
of how such systems actually work. This article, by focusing on the neglected areas of HR philosophy
and HR processes in the composition of HR systems, and by using a qualitative, employee-centred
approach in the collection and analysis of data, provides new insights into the working of HR systems.
Using data from interviews with 56 knowledge workers employed in the information and
communications technology sector in Ireland and the UK, we explore employee-level reactions to two
different types of HR systems. We highlight the various ways in which HR processes interact with HR
practices and the different outcomes that may result, and we identify the key role of HR philosophy in
HR system operation.

Intrusion Detection System for Network Security in Synchrophasor Systems

Synchrophasor systems will play a crucial role in next generation Smart Grid monitoring, protection and control. However these systems also introduce a multitude of potential vulnerabilities from malicious and inadvertent attacks, which may render erroneous operation or severe damage. This paper proposes a Synchrophasor Specific Intrusion Detection System (SSIDS) for malicious cyber attack and unintended misuse. The SSIDS comprises a heterogeneous whitelist and behavior-based approach to detect known attack types and unknown and so-called ‘zero-day’ vulnerabilities and attacks. The paper describes reconnaissance, Man-in-the-Middle (MITM) and Denial-of-Service (DoS) attack types executed against a practical synchrophasor system which are used to validate the real-time effectiveness of the proposed SSIDS cyber detection method.

Enhancing non-classicality in mechanical systems

We study the effects of post-selection measurements on both the non-classicality of the state of a mechanical oscillator and the entanglement between two mechanical systems that are part of a distributed optomechanical network. We address the cases of both Gaussian and non-Gaussian measurements, identifying in which cases simple photon counting and Geiger-like measurements are effective in distilling a strongly non-classical mechanical state and enhancing the purely mechanical entanglement between two elements of the network.

Entanglement Replication in Driven Dissipative Many-Body systems

We study the dissipative dynamics of two independent arrays of many-body systems, locally driven by a common entangled field. We showthat in the steady state the entanglement of the driving field is reproduced in an arbitrarily large series of inter-array entangled pairs over all distances. Local nonclassical driving thus realizes a scale-free entanglement replication and long-distance entanglement distribution mechanism that has immediate bearing on the implementation of quantum communication networks. 

Driven optomechanical systems for mechanical entanglement distribution

We consider the distribution of entanglement from a multimode optical driving source to a network of remote and independent optomechanical systems. By focusing on the tripartite case, we analyse the effects that the features of the optical input states have on the degree and sharing structure of the distributed, fully mechanical, entanglement. This study, which is conducted looking at the mechanical steady state, highlights the structure of the entanglement distributed among the nodes and determines the relative efficiency between bipartite and tripartite entanglement transfer. We discuss a few open points, some of which are directed towards the bypassing of such limitations.