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.

Multi-dimensional Goodness-of-Fit Tests for Spectrum Sensing Based on Stochastic Distances

In this paper, we study two multi-dimensional Goodness-of-Fit tests for spectrum sensing in cognitive radios. The multi-dimensional scenario refers to multiple CR nodes, each with multiple antennas, that record multiple observations from multiple primary users for spectrum sensing. These tests, viz., the Interpoint Distance (ID) based test and the h, f distance based tests are constructed based on the properties of stochastic distances. The ID test is studied in detail for a single CR node case, and a possible extension to handle multiple nodes is discussed. On the other hand, the h, f test is applicable in a multi-node setup. A robustness feature of the KL distance based test is discussed, which has connections with Middleton's class A model. Through Monte-Carlo simulations, the proposed tests are shown to outperform the existing techniques such as the eigenvalue ratio based test, John's test, and the sphericity test, in several scenarios.

Design of multi-frequency microstrip antennas using multiple rings

An electromagnetically coupled feed arrangement is proposed for simultaneously exciting multiple concentric ring antennas for multi-frequency operation. This has a multi-layer dielectric configuration in which a transmission line is embedded below the layer containing radiating rings. Energy coupled to these rings from the line beneath is optimised by suitably adjusting the location and dimensions of stubs on the line. It has been shown that the resonant frequencies of these rings do not change as several of these single-frequency antennas are combined to form a multi-resonant antenna. Furthermore, all radiators are forced to operate at their primary mode and some harmonics of the lower resonant frequency rings appearing within the frequency range are suppressed when combined. The experimental prototype antenna has three resonant frequencies at which it has good radiation characteristics.

Analyzing multiple spike trains with nonparametric granger causality

Simultaneous recordings of spike trains from multiple single neurons are becoming commonplace. Understanding the interaction patterns among these spike trains remains a key research area. A question of interest is the evaluation of information flow between neurons through the analysis of whether one spike train exerts causal influence on another. For continuous-valued time series data, Granger causality has proven an effective method for this purpose. However, the basis for Granger causality estimation is autoregressive data modeling, which is not directly applicable to spike trains. Various filtering options distort the properties of spike trains as point processes. Here we propose a new nonparametric approach to estimate Granger causality directly from the Fourier transforms of spike train data. We validate the method on synthetic spike trains generated by model networks of neurons with known connectivity patterns and then apply it to neurons limultaneously recorded from the thalamus and the primary somatosensory cortex of a squirrel monkey undergoing tactile stimulation.

Finite Signal-set Capacity of Two-user Gaussian Multiple Access Channel

The capacity region of a two-user Gaussian Multiple Access Channel (GMAC) with complex finite input alphabets and continuous output alphabet is studied. When both the users are equipped with the same code alphabet, it is shown that, rotation of one of the user’s alphabets by an appropriate angle can make the new pair of alphabets not only uniquely decodable, but will result in enlargement of the capacity region. For this set-up, we identify the primary problem to be finding appropriate angle(s) of rotation between the alphabets such that the capacity region is maximally enlarged. It is shown that the angle of rotation which provides maximum enlargement of the capacity region also minimizes the union bound on the probability of error of the sumalphabet and vice-verse. The optimum angle(s) of rotation varies with the SNR. Through simulations, optimal angle(s) of rotation that gives maximum enlargement of the capacity region of GMAC with some well known alphabets such as M-QAM and M-PSK for some M are presented for several values of SNR. It is shown that for large number of points in the alphabets, capacity gains due to rotations progressively reduce. As the number of points N tends to infinity, our results match the results in the literature wherein the capacity region of the Gaussian code alphabet doesn’t change with rotation for any SNR.

Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations

Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus.

Toll-Like Receptors 7, 8, and 9 Expression and Function in Primary Human Cervical Cancer Langerhans Cells Evidence of Anergy

Objective: Human papillomavirus oncoproteins E6 and E7 down modulate Toll-like receptor (TLR) 9 expression in infected keratinocytes. We explored the status of expression and function of TLR7, TLR8, and TLR9 in primary human Langerhans cells (LCs) isolated from cervical tumors. Methodology: Single-cell suspensions were made from fresh tissues of squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage IB2); myeloid dendritic cells were purified using CD1c magnetic activated cell separation kits. Langerhans cells were further flow sorted into CD1a(+)CD207(+) cells. Acute monocytic leukemia cell line THP-1-derived LCs (moLCs) formed the controls. mRNA from flow-sorted LCs was reverse transcribed to cDNA and TLR7, TLR8, and TLR9 amplified. Monocyte-derived Langerhans cells and cervical tumor LCs were stimulated with TLR7, TLR8, and TLR9 ligands. Culture supernatants were assayed for interleukin (IL) 1 beta, IL-6, IL-10, IL-12p70, interferon (IFN) alpha, interferon gamma, and tumor necrosis factor (TNF) alpha by Luminex multiplex bead array. Human papillomavirus was genotyped. Results: We have for the first time demonstrated that the acute monocytic leukemia cell line THP-1 can be differentiated into LCs in vitro. Although these moLCs. expressed all the 3 TLRs, tumor LCs expressed TLR7 and TLR8, but uniformly lacked TLR9. Also, moLCs secreted IL-6, IL-1 beta, and tumor necrosis factor alpha to TLR8 ligand and interferon alpha in response to TLR9 ligand; in contrast, tumor LCs did not express any cytokine to any of the 3 TLR ligands. Human papillomavirus type 16 was one of the common human papillomavirus types in all cases. Conclusions: Cervical tumor LCs lacked TLR9 expression and were functionally anergic to all the 3: TLR7, TLR8, and TLR9 ligands, which may play a crucial role in immune tolerance. The exact location of block(s) in TLR7 and TLR8 signaling needs to be investigated, which would have important immunotherapeutic implications.

Multiple transmitter localization and communication footprint identification using sparse reconstruction techniques

This paper considers the problem of identifying the footprints of communication of multiple transmitters in a given geographical area. To do this, a number of sensors are deployed at arbitrary but known locations in the area, and their individual decisions regarding the presence or absence of the transmitters' signal are combined at a fusion center to reconstruct the spatial spectral usage map. One straightforward scheme to construct this map is to query each of the sensors and cluster the sensors that detect the primary's signal. However, using the fact that a typical transmitter footprint map is a sparse image, two novel compressive sensing based schemes are proposed, which require significantly fewer number of transmissions compared to the querying scheme. A key feature of the proposed schemes is that the measurement matrix is constructed from a pseudo-random binary phase shift applied to the decision of each sensor prior to transmission. The measurement matrix is thus a binary ensemble which satisfies the restricted isometry property. The number of measurements needed for accurate footprint reconstruction is determined using compressive sampling theory. The three schemes are compared through simulations in terms of a performance measure that quantifies the accuracy of the reconstructed spatial spectral usage map. It is found that the proposed sparse reconstruction technique-based schemes significantly outperform the round-robin scheme.

Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3'-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.

Synthon identification in co-crystals and polymorphs with IR spectroscopy. Primary amides as a case study

IR spectroscopy has been widely employed to distinguish between different crystal forms such as polymorphs, clathrates, hydrates and co-crystals. IR has been used to monitor co-crystal formation and single synthon detection. In this work, we have developed a strategy to identify multiple supramolecular synthons in polymorphs and co-crystals with this technique. The identification of multiple synthons in co-crystals with IR is difficult for several reasons. In this paper, a four step method involving well assigned IR spectral markers that correspond to bonds in a synthon is used. IR spectra of three forms of the co-crystal system, 4-hydroxybenzoic acid: 4,4'-bipyridine (2 : 1), show clear differences that may be attributed to differences in the synthon combinations existing in the forms (synthon polymorphism). These differences were picked out from the three IR spectra and the bands analysed and assigned to synthons. Our method first identifies IR marker bands corresponding to (covalent) bonds in known/model crystals and then the markers are mapped in known co-crystals having single synthons. Thereafter, the IR markers are queried in known co-crystals with multiple synthons. Finally they are queried in unknown co-crystals with multiple synthons. In the last part of the study, the N-H stretching absorptions of primary amides that crystallize with the amide dimers linked in a ladder like chain show two specific absorptions which are used as marker absorptions and all variations of this band structure have been used to provide details on the environment around the dimer. The extended dimer can accordingly be easily distinguished from the isolated dimer.

Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of ``how much'' information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on ``what'' is coded by primary afferents. Amongst the kinematic variables tested-position, velocity, and acceleration-primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80-90%. The final 10-20% were found to be due to non-linear coding by spike bursts.

mulPBA: an efficient multiple protein structure alignment method based on a structural alphabet

The increasing number of available protein structures requires efficient tools for multiple structure comparison. Indeed, multiple structural alignments are essential for the analysis of function, evolution and architecture of protein structures. For this purpose, we proposed a new web server called multiple Protein Block Alignment (mulPBA). This server implements a method based on a structural alphabet to describe the backbone conformation of a protein chain in terms of dihedral angles. This sequence-like' representation enables the use of powerful sequence alignment methods for primary structure comparison, followed by an iterative refinement of the structural superposition. This approach yields alignments superior to most of the rigid-body alignment methods and highly comparable with the flexible structure comparison approaches. We implement this method in a web server designed to do multiple structure superimpositions from a set of structures given by the user. Outputs are given as both sequence alignment and superposed 3D structures visualized directly by static images generated by PyMol or through a Jmol applet allowing dynamic interaction. Multiple global quality measures are given. Relatedness between structures is indicated by a distance dendogram. Superimposed structures in PDB format can be also downloaded, and the results are quickly obtained. mulPBA server can be accessed at www.dsimb.inserm.fr/dsimb_tools/mulpba/.

Modeling Time-Varying Aggregate Interference in Cognitive Radio Systems, and Application to Primary Exclusive Zone Design

Accurately characterizing the time-varying interference caused to the primary users is essential in ensuring a successful deployment of cognitive radios (CR). We show that the aggregate interference at the primary receiver (PU-Rx) from multiple, randomly located cognitive users (CUs) is well modeled as a shifted lognormal random process, which is more accurate than the lognormal and the Gaussian process models considered in the literature, even for a relatively dense deployment of CUs. It also compares favorably with the asymptotically exact stable and symmetric truncated stable distribution models, except at high CU densities. Our model accounts for the effect of imperfect spectrum sensing, which depends on path-loss, shadowing, and small-scale fading of the link from the primary transmitter to the CU; the interweave and underlay modes or CR operation, which determine the transmit powers of the CUs; and time-correlated shadowing and fading of the links from the CUs to the PU-Rx. It leads to expressions for the probability distribution function, level crossing rate, and average exceedance duration. The impact of cooperative spectrum sensing is also characterized. We validate the model by applying it to redesign the primary exclusive zone to account for the time-varying nature of interference.

Emerging roles of MCPH1: Expedition from primary microcephaly to cancer

Genetic mutations in microcephalinl (MCPH1) cause primary autosomal recessive microcephaly which is characterized by a marked reduction in brain size. MCPH1 encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also, it is a key regulator of DNA repair pathway and cell cycle checkpoints. Interestingly, in the past few years, many research studies have explored the role of MCPH1, a neurodevelopmental gene in several cancers and its tumor suppressor functions have been elucidated. Given the diverse new emerging roles, it becomes critical to review and summarize the multiple roles of MCPH1 that is currently lacking in the literature. In this review after systematic analysis of literature, we summarise the multiple functional roles of MCPH1 in centrosomal, DNA repair and apoptotic pathways. Additionally, we discuss the considerable efforts taken to understand the implications of MCPH1 in diseases such as primary microcephaly and its other emerging association with cancer and otitis media. The promising view is that MCPH1 has distinct roles and its clinical associations in various diseases makes it an attractive therapeutic target. (C) 2014 Elsevier GmbH. All rights reserved.

A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors

Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the ``Gain-offunction'' mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12 amino-acid insertion demonstrated ``opening'' resulting in exposure of the S2-cleavage site leading to activated Notch1 signaling. The MAb, at low concentrations (1-2 mu g/ml), inhibited elevated ligand-independent Notch1 signaling of NRR mutants, augmented effect of Thapsigargin, an inhibitor of mutant Notch1, but had no effect on the wild-type Notch1. The antibody decreased proliferation of the primary T-ALL cells and depleted leukemia initiating CD34/CD44 high population. At relatively high concentrations, (10-20 mu g/ml), the MAb affected Notch1 signaling in the breast and colon cancer cell lines. The Notch-high cells sorted from solid-tumor cell lines exhibited characteristics of cancer stem cells, which were inhibited by the MAb. The antibody also increased the sensitivity to Doxorubucinirubicin. Further, the MAb impeded the growth of xenografts from breast and colon cancer cells potentiated regression of the tumors along with Doxorubucin. Thus, this antibody is potential immunotherapeutic tool for different cancers.