Chemical Shifts to Metabolic Pathways: Identifying Metabolic Pathways Directly from a Single 2D NMR Spectrum

Identifying cellular processes in terms of metabolic pathways is one of the avowed goals of metabolomics studies. Currently, this is done after relevant metabolites are identified to allow their mapping onto specific pathways. This task is daunting due to the complex nature of cellular processes and the difficulty in establishing the identity of individual metabolites. We propose here a new method: ChemSMP (Chemical Shifts to Metabolic Pathways), which facilitates rapid analysis by identifying the active metabolic pathways directly from chemical shifts obtained from a single two-dimensional (2D) C-13-H-1] correlation NMR spectrum without the need for identification and assignment of individual metabolites. ChemSMP uses a novel indexing and scoring system comprised of a ``uniqueness score'' and a ``coverage score''. Our method is demonstrated on metabolic pathways data from the Small Molecule Pathway Database (SMPDB) and chemical shifts from the Human Metabolome Database (HMDB). Benchmarks show that ChemSMP has a positive prediction rate of >90% in the presence of deduttered data and can sustain the same at 60-70% even in the presence of noise, such as deletions of peaks and chemical shift deviations. The method tested on NMR data acquired for a mixture of 20 amino acids shows a success rate of 93% in correct recovery of pathways. When used on data obtained from the cell lysate of an unexplored oncogenic cell line, it revealed active metabolic pathways responsible for regulating energy homeostasis of cancer cells. Our unique tool is thus expected to significantly enhance analysis of NMIR-based metabolomics data by reducing existing impediments.

Error exponent analysis of energy-based Bayesian decentralized spectrum sensing under fading

This paper considers decentralized spectrum sensing, i.e., detection of occupancy of the primary users' spectrum by a set of Cognitive Radio (CR) nodes, under a Bayesian set-up. The nodes use energy detection to make their individual decisions, which are combined at a Fusion Center (FC) using the K-out-of-N fusion rule. The channel from the primary transmitter to the CR nodes is assumed to undergo fading, while that from the nodes to the FC is assumed to be error-free. In this scenario, a novel concept termed as the Error Exponent with a Confidence Level (EECL) is introduced to evaluate and compare the performance of different detection schemes. Expressions for the EECL under general fading conditions are derived. As a special case, it is shown that the conventional error exponent both at individual sensors, and at the FC is zero. Further, closed-form lower bounds on the EECL are derived under Rayleigh fading and lognormal shadowing. As an example application, it answers the question of whether to use pilot-signal based narrowband sensing, where the signal undergoes Rayleigh fading, or to sense over the entire bandwidth of a wideband signal, where the signal undergoes lognormal shadowing. Theoretical results are validated using Monte Carlo simulations. (C) 2015 Elsevier B.V. All rights reserved.

Design and implementation of spectrum sensing for cognitive radios with a frequency-hopping primary system

In this work, spectrum sensing for cognitive radios is considered in the presence of multiple Primary Users (PU) using frequency-hopping communication over a set of frequency bands. The detection performance of the Fast Fourier Transform (FFT) Average Ratio (FAR) algorithm is obtained in closed-form, for a given FFT size and number of PUs. The effective throughput of the Secondary Users (SU) is formulated as an optimization problem with a constraint on the maximum allowable interference on the primary network. Given the hopping period of the PUs, the sensing duration that maximizes the SU throughput is derived. The results are validated using Monte Carlo simulations. Further, an implementation of the FAR algorithm on the Lyrtech (now, Nutaq) small form factor software defined radio development platform is presented, and the performance recorded through the hardware is observed to corroborate well with that obtained through simulations, allowing for implementation losses. (C) 2015 Elsevier B.V. All rights reserved.

Potency and pharmacokinetics of broad spectrum and isoform-specific p110 gamma and delta inhibitors in cancers

Emerging data on cancer suggesting that target-based therapy is promising strategy in cancer treatment. PI3K-AKT pathway is extensively studied in many cancers; several inhibitors target this pathway in different levels. Recent finding on this pathway uncovered the therapeutic applications of PI3K-specific inhibitors; PI3K, AKT, and mTORC broad spectrum inhibitors. Noticeably, class I PI3K isoforms, p110 and p110 catalytic subunits have rational therapeutic application than other isoforms. Therefore, three classes of inhibitors: isoform-specific, dual-specific and broad spectrum were selected for molecular docking and dynamics. First, p110 structure was modelled; active site was analyzed. Then, molecular docking of each class of inhibitors were studied; the docked complexes were further used in 1.2ns molecular dynamics simulation to report the potency of each class of inhibitor. Remarkably, both the studies retained the similar kind of protein ligand interactions. GDC-0941, XL-147 (broad spectrum); TG100-115 (dual-specific); and AS-252424, PIK-294 (isoform-specific) were found to be potential inhibitors of p110 and p110, respectively. In addition to that pharmacokinetic properties are within recommended ranges. Finally, molecular phylogeny revealed that p110 and p110 are evolutionarily divergent; they probably need separate strategies for drug development.

Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing

Cell lines derived from tumor tissues have been used as a valuable system to study gene regulation and cancer development. Comprehensive characterization of the genetic background of cell lines could provide clues on novel genes responsible for carcinogenesis and help in choosing cell lines for particular studies. Here, we have carried out whole exome and RNA sequencing of commonly used glioblastoma (GBM) cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotide variations (SNVs), indels, differential gene expression, gene fusions and RNA editing events. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) were potentially cancer-specific. The cell lines showed frequent SNVs and indels in some of the genes that are known to be altered in GBM-EGFR, TP53, PTEN, SPTA1 and NF1. Chromatin modifying genes-ATRX, MLL3, MLL4, SETD2 and SRCAP also showed alterations. While no cell line carried IDH1 mutations, five cell lines showed hTERT promoter activating mutations with a concomitant increase in hTERT transcript levels. Five significant gene fusions were found of which NUP93-CYB5B was validated. An average of 18,949 RNA editing events was also obtained. Thus we have generated a comprehensive catalogue of genetic alterations for six GBM cell lines.

Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing

Cell lines derived from tumor tissues have been used as a valuable system to study gene regulation and cancer development. Comprehensive characterization of the genetic background of cell lines could provide clues on novel genes responsible for carcinogenesis and help in choosing cell lines for particular studies. Here, we have carried out whole exome and RNA sequencing of commonly used glioblastoma (GBM) cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotide variations (SNVs), indels, differential gene expression, gene fusions and RNA editing events. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) were potentially cancer-specific. The cell lines showed frequent SNVs and indels in some of the genes that are known to be altered in GBM-EGFR, TP53, PTEN, SPTA1 and NF1. Chromatin modifying genes-ATRX, MLL3, MLL4, SETD2 and SRCAP also showed alterations. While no cell line carried IDH1 mutations, five cell lines showed hTERT promoter activating mutations with a concomitant increase in hTERT transcript levels. Five significant gene fusions were found of which NUP93-CYB5B was validated. An average of 18,949 RNA editing events was also obtained. Thus we have generated a comprehensive catalogue of genetic alterations for six GBM cell lines.

Time-Instant Sampling Based Encoding of Time-Varying Acoustic Spectrum

The inner ear has been shown to characterize an acoustic stimuli by transducing fluid motion in the inner ear to mechanical bending of stereocilia on the inner hair cells (IHCs). The excitation motion/energy transferred to an IHC is dependent on the frequency spectrum of the acoustic stimuli, and the spatial location of the IHC along the length of the basilar membrane (BM). Subsequently, the afferent auditory nerve fiber (ANF) bundle samples the encoded waveform in the IHCs by synapsing with them. In this work we focus on sampling of information by afferent ANFs from the IHCs, and show computationally that sampling at specific time instants is sufficient for decoding of time-varying acoustic spectrum embedded in the acoustic stimuli. The approach is based on sampling the signal at its zero-crossings and higher-order derivative zero-crossings. We show results of the approach on time-varying acoustic spectrum estimation from cricket call signal recording. The framework gives a time-domain and non-spatial processing perspective to auditory signal processing. The approach works on the full band signal, and is devoid of modeling any bandpass filtering mimicking the BM action. Instead, we motivate the approach from the perspective of event-triggered sampling by afferent ANFs on the stimuli encoded in the IHCs. Though the approach gives acoustic spectrum estimation but it is shallow on its complete understanding for plausible bio-mechanical replication with current mammalian auditory mechanics insights.

Comparison of Matching Pursuit Algorithm with Other Signal Processing Techniques for Computation of the Time-Frequency Power Spectrum of Brain Signals

Signals recorded from the brain often show rhythmic patterns at different frequencies, which are tightly coupled to the external stimuli as well as the internal state of the subject. In addition, these signals have very transient structures related to spiking or sudden onset of a stimulus, which have durations not exceeding tens of milliseconds. Further, brain signals are highly nonstationary because both behavioral state and external stimuli can change on a short time scale. It is therefore essential to study brain signals using techniques that can represent both rhythmic and transient components of the signal, something not always possible using standard signal processing techniques such as short time fourier transform, multitaper method, wavelet transform, or Hilbert transform. In this review, we describe a multiscale decomposition technique based on an over-complete dictionary called matching pursuit (MP), and show that it is able to capture both a sharp stimulus-onset transient and a sustained gamma rhythm in local field potential recorded from the primary visual cortex. We compare the performance of MP with other techniques and discuss its advantages and limitations. Data and codes for generating all time-frequency power spectra are provided.

Distributed Nonparametric Sequential Spectrum Sensing under Electromagnetic Interference

We propose a distributed sequential algorithm for quick detection of spectral holes in a Cognitive Radio set up. Two or more local nodes make decisions and inform the fusion centre (FC) over a reporting Multiple Access Channel (MAC), which then makes the final decision. The local nodes use energy detection and the FC uses mean detection in the presence of fading, heavy-tailed electromagnetic interference (EMI) and outliers. The statistics of the primary signal, channel gain and the EMI is not known. Different nonparametric sequential algorithms are compared to choose appropriate algorithms to be used at the local nodes and the Fe. Modification of a recently developed random walk test is selected for the local nodes for energy detection as well as at the fusion centre for mean detection. We show via simulations and analysis that the nonparametric distributed algorithm developed performs well in the presence of fading, EMI and outliers. The algorithm is iterative in nature making the computation and storage requirements minimal.

Green Nanosilver as Reinforcing Eco-Friendly Additive to Epoxy Coating for Augmented Anticorrosive and Antimicrobial Behavior

Epoxy resin GY250 representing diglycidyl ethers of bisphenol-A (DGEBA) was reinforced with 1, 3 and 5 wt % of surface functionalized silver nanoparticles (F-AgNPs) which were synthesized using Couroupita guianensis leaves extract with a view of augmenting the corrosion control property of the epoxy resin and also imparting antimicrobial activity to epoxy coatings on mild steel. Corrosion resistance of the coatings was evaluated by EIS, potentiodynamic polarization studies and cross scratch tests. AFM, SEM, HRTEM and EDX were utilized to investigate the surface topography, morphology and elemental composition of the coatings on MS specimens. Results showed that the corrosion resistance, hardness and T-g of the DGEBA/F-AgNPs coatings increased at 1 wt % of F-AgNPs. The DGEBA/F-AgNPs coatings also offered manifold antimicrobial protection to the MS surfaces by inhibiting the growth of biofilm forming bacteria like P. aeruginosa, B. subtilis, the most common human pathogen E. coli and the most virulent human pathogenic yeast C. albicans.