Coordinate Hyperactivation of Notch1 and Ras/MAPK Pathways Correlates with Poor Patient Survival: Novel Therapeutic Strategy for Aggressive Breast Cancers

Aberrant activation of Notch and Ras pathways has been detected in breast cancers. A synergy between these two pathways has also been shown in breast cell transformation in culture. Yet, the clinical relevance of Notch-Ras cooperation in breast cancer progression remains unexplored. In this study, we show that coordinate hyperactivation of Notch1 and Ras/MAPK pathways in breast cancer patient specimens, as assessed by IHC for cleaved Notch1 and pErk1/2, respectively, correlated with early relapse to vital organs and poor overall survival. Interestingly, majority of such Notch1 (high)Erk(high) cases encompassed the highly aggressive triple-negative breast cancers (TNBC), and were enriched in stem cell markers. We further show that combinatorial inhibition of Notch1 and Ras/MAPK pathways, using a novel mAb against Notch1 and a MEK inhibitor, respectively, led to a significant reduction in proliferation and survival of breast cancer cells compared with individual inhibition. Combined inhibition also abrogated sphere-forming potential, and depleted the putative cancer stem-like cell subpopulation. Most importantly, combinatorial inhibition of Notch1 and Ras/MAPK pathways completely blocked tumor growth in a panel of breast cancer xenografts, including the TNBCs. Thus, our study identifies coordinate hyperactivation of Notch1 and Ras/MAPK pathways as novel biomarkers for poor breast cancer outcome. Furthermore, based on our preclinical data, we propose combinatorial targeting of these two pathways as a treatment strategy for highly aggressive breast cancers, particularly the TNBCs that currently lack any targeted therapeutic module. (C) 2014 AACR.

Exact Phase Retrieval for a Class of 2-D Parametric Signals

We address the problem of two-dimensional (2-D) phase retrieval from magnitude of the Fourier spectrum. We consider 2-D signals that are characterized by first-order difference equations, which have a parametric representation in the Fourier domain. We show that, under appropriate stability conditions, such signals can be reconstructed uniquely from the Fourier transform magnitude. We formulate the phase retrieval problem as one of computing the parameters that uniquely determine the signal. We show that the problem can be solved by employing the annihilating filter method, particularly for the case when the parameters are distinct. For the more general case of the repeating parameters, the annihilating filter method is not applicable. We circumvent the problem by employing the algebraically coupled matrix pencil (ACMP) method. In the noiseless measurement setup, exact phase retrieval is possible. We also establish a link between the proposed analysis and 2-D cepstrum. In the noisy case, we derive Cramer-Rao lower bounds (CRLBs) on the estimates of the parameters and present Monte Carlo performance analysis as a function of the noise level. Comparisons with state-of-the-art techniques in terms of signal reconstruction accuracy show that the proposed technique outperforms the Fienup and relaxed averaged alternating reflections (RAAR) algorithms in the presence of noise.

Design of an Automated Dispenser Unit

This paper presents our work on developing an automated micro positioner and a low cost disposable dispenser module having a disposable dispenser core. The dispenser core is made up of Polydimethylsiloxane (PDMS). Once the user specifies the dispensing location in the Graphical User Interface (GUI), the movement of the micropositioner is automatic. The design, fabrication and characterization results of the dispenser module are also presented. The dispensing experiments are performed with Di-Ethanol Amine as the working reagent. The minimum dispensed volume achieved is about 4 nL.

Maze solving automatons for self-healing of open interconnects: Modular add-on for circuit boards

We present the circuit board integration of a self-healing mechanism to repair open faults. The electric field driven mechanism physically restores fractured interconnects in electronic circuits and has the ability to solve mazes. The repair is performed by conductive particles dispersed in an insulating fluid. We demonstrate the integration of the healing module onto printed circuit boards and the ability of maze solving. We model and perform experiments on the influence of the geometry of conductive particles as well as the terminal impedances of the route on the healing efficiency. The typical heal rate is 10 mu m/s with healed route having mean resistance of 8 k Omega across a 200 micron gap and depending on the materials and concentrations used. (C) 2015 AIP Publishing LLC.

A faster algorithm for testing polynomial representability of functions over finite integer rings

Given a function from Z(n) to itself one can determine its polynomial representability by using Kempner function. In this paper we present an alternative characterization of polynomial functions over Z(n) by constructing a generating set for the Z(n)-module of polynomial functions. This characterization results in an algorithm that is faster on average in deciding polynomial representability. We also extend the characterization to functions in several variables. (C) 2015 Elsevier B.V. All rights reserved.

Graphene based multifunctional flame sensor

Recently, graphene has attracted much attention due to its unique electrical and thermal properties along with its high surface area, and hence presents an ideal sensing material. We report a novel configuration of a graphene based flame sensor by exploiting the response of few layer graphene to a flame along two different directions, where flame detection results from a difference in heat transfer mechanisms. A complete sensor module was developed with a signal conditioning circuit that compensates for any drift in the baseline of the sensor, along with a flame detection algorithm implemented in a microcontroller to detect the flame. A pre-defined threshold for either of the sensors is tunable, which can be varied based on the nature of the flame, hence presenting a system that can be used for detection of any kind of flame. This finding also presents a scalable method that opens avenues to modify complicated sensing schemes.

Spectral Zero-Crossings: Localization Properties and Applications

We present an analysis of the rate of sign changes in the discrete Fourier spectrum of a sequence. The sign changes of either the real or imaginary parts of the spectrum are considered, and the rate of sign changes is termed as the spectral zero-crossing rate (SZCR). We show that SZCR carries information pertaining to the locations of transients within the temporal observation window. We show duality with temporal zero-crossing rate analysis by expressing the spectrum of a signal as a sum of sinusoids with random phases. This extension leads to spectral-domain iterative filtering approaches to stabilize the spectral zero-crossing rate and to improve upon the location estimates. The localization properties are compared with group-delay-based localization metrics in a stylized signal setting well-known in speech processing literature. We show applications to epoch estimation in voiced speech signals using the SZCR on the integrated linear prediction residue. The performance of the SZCR-based epoch localization technique is competitive with the state-of-the-art epoch estimation techniques that are based on average pitch period.

Experimental Study on Switching Characteristics of an Inverter Leg Consisting of IGBTs of Dissimilar Makes

Usually the top and bottom IGBT devices in an inverter leg are of the same make (i.e. from same manufacturer). At low power level, these two devices even may be contained in the same module. However at high power levels the top and bottom devices are in separate modules. Sometimes, in the event of device failure, device of particular make may be replaced by one of another make, but of same ratings (on account of non-availability of the original make). This paper investigates the effect of such intermixing of two different makes of high power IGBTs in an inverter leg on the switching characteristics. The switching transitions between IGBT and diode of similar make and those of IGBT and diode of dissimilar make are compared experimentally at various DC link voltages and currents. The comparisons are made in terms of, IGBT peak turn-on di/dt, IGBT peak turn-off di/dt, peak diode reverse recovery current (I-rr), peak IGBT voltage overshoot and switching energy losses.

Unified Continuum Damage Model for Matrix Cracking in Composite Rotor Blades

This paper deals with modeling of the first damage mode, matrix micro-cracking, in helicopter rotor/wind turbine blades and how this effects the overall cross-sectional stiffness. The helicopter/wind turbine rotor system operates in a highly dynamic and unsteady environment leading to severe vibratory loads present in the system. Repeated exposure to this loading condition can induce damage in the composite rotor blades. These rotor/turbine blades are generally made of fiber-reinforced laminated composites and exhibit various competing modes of damage such as matrix micro-cracking, delamination, and fiber breakage. There is a need to study the behavior of the composite rotor system under various key damage modes in composite materials for developing Structural Health Monitoring (SHM) system. Each blade is modeled as a beam based on geometrically non-linear 3-D elasticity theory. Each blade thus splits into 2-D analyzes of cross-sections and non-linear 1-D analyzes along the beam reference curves. Two different tools are used here for complete 3-D analysis: VABS for 2-D cross-sectional analysis and GEBT for 1-D beam analysis. The physically-based failure models for matrix in compression and tension loading are used in the present work. Matrix cracking is detected using two failure criterion: Matrix Failure in Compression and Matrix Failure in Tension which are based on the recovered field. A strain variable is set which drives the damage variable for matrix cracking and this damage variable is used to estimate the reduced cross-sectional stiffness. The matrix micro-cracking is performed in two different approaches: (i) Element-wise, and (ii) Node-wise. The procedure presented in this paper is implemented in VABS as matrix micro-cracking modeling module. Three examples are presented to investigate the matrix failure model which illustrate the effect of matrix cracking on cross-sectional stiffness by varying the applied cyclic

Router Attack toward NoC-enabled MPSoC and Monitoring Countermeasures against such Threat

The growing number of applications and processing units in modern Multiprocessor Systems-on-Chips (MPSoCs) come along with reduced time to market. Different IP cores can come from different vendors, and their trust levels are also different, but typically they use Network-on-Chip (NoC) as their communication infrastructure. An MPSoC can have multiple Trusted Execution Environments (TEEs). Apart from performance, power, and area research in the field of MPSoC, robust and secure system design is also gaining importance in the research community. To build a secure system, the designer must know beforehand all kinds of attack possibilities for the respective system (MPSoC). In this paper we survey the possible attack scenarios on present-day MPSoCs and investigate a new attack scenario, i.e., router attack targeted toward NoC architecture. We show the validity of this attack by analyzing different present-day NoC architectures and show that they are all vulnerable to this type of attack. By launching a router attack, an attacker can control the whole chip very easily, which makes it a very serious issue. Both routing tables and routing logic-based routers are vulnerable to such attacks. In this paper, we address attacks on routing tables. We propose different monitoring-based countermeasures against routing table-based router attack in an MPSoC having multiple TEEs. Synthesis results show that proposed countermeasures, viz. Runtime-monitor, Restart-monitor, Intermediate manager, and Auditor, occupy areas that are 26.6, 22, 0.2, and 12.2 % of a routing table-based router area. Apart from these, we propose Ejection address checker and Local monitoring module inside a router that cause 3.4 and 10.6 % increase of a router area, respectively. Simulation results are also given, which shows effectiveness of proposed monitoring-based countermeasures.

Physical Layer Data Fusion Via Distributed Co-Phasing With General Signal Constellations

This paper studies a pilot-assisted physical layer data fusion technique known as Distributed Co-Phasing (DCP). In this two-phase scheme, the sensors first estimate the channel to the fusion center (FC) using pilots sent by the latter; and then they simultaneously transmit their common data by pre-rotating them by the estimated channel phase, thereby achieving physical layer data fusion. First, by analyzing the symmetric mutual information of the system, it is shown that the use of higher order constellations (HOC) can improve the throughput of DCP compared to the binary signaling considered heretofore. Using an HOC in the DCP setting requires the estimation of the composite DCP channel at the FC for data decoding. To this end, two blind algorithms are proposed: 1) power method, and 2) modified K-means algorithm. The latter algorithm is shown to be computationally efficient and converges significantly faster than the conventional K-means algorithm. Analytical expressions for the probability of error are derived, and it is found that even at moderate to low SNRs, the modified K-means algorithm achieves a probability of error comparable to that achievable with a perfect channel estimate at the FC, while requiring no pilot symbols to be transmitted from the sensor nodes. Also, the problem of signal corruption due to imperfect DCP is investigated, and constellation shaping to minimize the probability of signal corruption is proposed and analyzed. The analysis is validated, and the promising performance of DCP for energy-efficient physical layer data fusion is illustrated, using Monte Carlo simulations.

Joint Channel Estimation and Data Detection in MIMO-OFDM Systems: A Sparse Bayesian Learning Approach

The impulse response of wireless channels between the N-t transmit and N-r receive antennas of a MIMO-OFDM system are group approximately sparse (ga-sparse), i.e., NtNt the channels have a small number of significant paths relative to the channel delay spread and the time-lags of the significant paths between transmit and receive antenna pairs coincide. Often, wireless channels are also group approximately cluster-sparse (gac-sparse), i.e., every ga-sparse channel consists of clusters, where a few clusters have all strong components while most clusters have all weak components. In this paper, we cast the problem of estimating the ga-sparse and gac-sparse block-fading and time-varying channels in the sparse Bayesian learning (SBL) framework and propose a bouquet of novel algorithms for pilot-based channel estimation, and joint channel estimation and data detection, in MIMO-OFDM systems. The proposed algorithms are capable of estimating the sparse wireless channels even when the measurement matrix is only partially known. Further, we employ a first-order autoregressive modeling of the temporal variation of the ga-sparse and gac-sparse channels and propose a recursive Kalman filtering and smoothing (KFS) technique for joint channel estimation, tracking, and data detection. We also propose novel, parallel-implementation based, low-complexity techniques for estimating gac-sparse channels. Monte Carlo simulations illustrate the benefit of exploiting the gac-sparse structure in the wireless channel in terms of the mean square error (MSE) and coded bit error rate (BER) performance.

Experimental characterisation and performance evaluation of a coaxial current transformer for measurement of insulated gate bipolar transistor switching current

Measurement of device current during switching characterisation of an insulated gate bipolar transistor (IGBT) requires a current sensor with low insertion impedance and high bandwidth. This study presents an experimental procedure for evaluating the performance of a coaxial current transformer (CCT), designed for the above purpose. A prototype CCT, which can be mounted directly on a power terminal of a 1200 V/50 A half-bridge IGBT module, is characterised experimentally. The measured characteristics include insertion impedance, gain and phase of the CCT at different frequencies. The bounds of linearity within which the CCT can operate without saturation are determined theoretically, and are also verified experimentally. The experimental study on linearity of the CCT requires a high-amplitude current source. A proportional-resonant (PR) controller-based current-controlled half-bridge inverter is developed for this purpose. A systematic procedure for selection of PR controller parameters is also reported in this study. This set-up is helpful to determine the limit of linearity and also to measure the frequency response of the CCT at realistic amplitudes of current in the low-frequency range.

Exact Phase Retrieval in Principal Shift-Invariant Spaces

We address the problem of phase retrieval from Fourier transform magnitude spectrum for continuous-time signals that lie in a shift-invariant space spanned by integer shifts of a generator kernel. The phase retrieval problem for such signals is formulated as one of reconstructing the combining coefficients in the shift-invariant basis expansion. We develop sufficient conditions on the coefficients and the bases to guarantee exact phase retrieval, by which we mean reconstruction up to a global phase factor. We present a new class of discrete-domain signals that are not necessarily minimum-phase, but allow for exact phase retrieval from their Fourier magnitude spectra. We also establish Hilbert transform relations between log-magnitude and phase spectra for this class of discrete signals. It turns out that the corresponding continuous-domain counterparts need not satisfy a Hilbert transform relation; notwithstanding, the continuous-domain signals can be reconstructed from their Fourier magnitude spectra. We validate the reconstruction guarantees through simulations for some important classes of signals such as bandlimited signals and piecewise-smooth signals. We also present an application of the proposed phase retrieval technique for artifact-free signal reconstruction in frequency-domain optical-coherence tomography (FDOCT).

Divergence in Patterns of Leaf Growth Polarity Is Associated with the Expression Divergence of miR396

Lateral appendages often show allometric growth with a specific growth polarity along the proximo-distal axis. Studies on leaf growth in model plants have identified a basipetal growth direction with the highest growth rate at the proximal end and progressively lower rates toward the distal end. Although the molecular mechanisms governing such a growth pattern have been studied recently, variation in leaf growth polarity and, therefore, its evolutionary origin remain unknown. By surveying 75 eudicot species, here we report that leaf growth polarity is divergent. Leaf growth in the proximo-distal axis is polar, with more growth arising from either the proximal or the distal end; dispersed with no apparent polarity; or bidirectional, with more growth contributed by the central region and less growth at either end. We further demonstrate that the expression gradient of the miR396-GROWTH-REGULATING FACTOR module strongly correlates with the polarity of leaf growth. Altering the endogenous pattern of miR396 expression in transgenic Arabidopsis thaliana leaves only partially modified the spatial pattern of cell expansion, suggesting that the diverse growth polarities might have evolved via concerted changes in multiple gene regulatory networks.