Signal Generation Process Research Articles

A non-randomized interventional study to promote the knowledge, attitude and practices of community pharmacists towards pharmacovigilance

Pharmacovigilance promotes the safe and effective use of medicines and thereby optimizes the treatment quality. However, lack of awareness among community pharmacists towards pharmacovigilance decreases the proportion of adverse drug reactions reported and impairs the signal detection process. Hence this study was designed to assess and promote the awareness and attitude of community pharmacists towards pharmacovigilance. This educational interventional study was carried out with 102 community pharmacists across Chennai. A pre-validated three domain-containing questionnaire, 20 items was used to assess the knowledge, attitude and practice before and after the educational intervention. Knowledge, attitude and practices of community pharmacists towards pharmacovigilance was significantly increased after the educational intervention (P<0.05, 95%CI). Median difference in an overall score of knowledge and practice was observed to be 4 and 4.5, respectively. Though the frequency of ADR reporting was not found to be greatly increased in our study, mass educational programs with adequate sampling intervals are needed to strengthen the signal generation process.

Technique of Informative Features Selection in Geoacoustic Emission Signals

Studies of geoacoustic emission in a seismically active region in Kamchatka show that geoacoustic signals produce pronounced pulse anomalies during the earthquake preparation and post-seismic relaxation of the local stresses field at the observation point. The qualitative selection of such anomalies is complicated by a strong distortion and weakening of the signal amplitude. A review of existing acoustic emission analysis methods shows that most often researchers turn to the analysis of more accessible to study statistical properties and energy of signals. The distinctive features of the approach proposed by the authors are the extraction of informative features based on the analysis of time and frequency-time structures of geoacoustic signals and the description of various forms of recognizable pulses by a limited pattern set. This study opens up new ideas to develop methods for detecting anomalous behavior of geoacoustic signals, including anomalies before earthquakes.
 The paper describes a technique of information extraction from geoacoustic emission pulse streams of sound frequency range. A geoacoustic pulse mathematical model, reflecting the signal generation process from a variety of elementary sources, is presented. A solution to the problem of detection of geoacoustic signal informative features is presented by the means of description of signal fragments by the matrixes of local extrema amplitude ratios and of interval ratios between them. The result of applying the developed algorithm to describe automatically the structure of the detected pulses and to form a pattern set is shown. The patterns characterize the features of geoacoustic emission signals observed at IKIR FEB RAS field stations. A technique of reduction of the detected pulse set dimensions is presented. It allows us to find patterns similar in structure. A solution to the problem of processing of a large data flow by unifying pulses description and their systematization is proposed. A method to identify a geoacoustic emission pulse model using sparse approximation schemes is suggested. An algorithmic solution of the problem of reducing the computational complexity of the matching pursuit method is described. It is to include an iterative refinement algorithm for the solution at each step in the method. The results of the research allowed the authors to create a tool to investigate the dynamic properties of geoacoustic emission signal in order to develop earthquake prediction detectors.

Application of nonlinear methods to discriminate fractionated electrograms in paroxysmal versus persistent atrial fibrillation

Background and ObjectiveComplex fractionated atrial electrograms (CFAE) may contain information concerning the electrophysiological substrate of atrial fibrillation (AF); therefore they are of interest to guide catheter ablation treatment of AF. Electrogram signals are shaped by activation events, which are dynamical in nature. This makes it difficult to establish those signal properties that can provide insight into the ablation site location. Nonlinear measures may improve information. To test this hypothesis, we used nonlinear measures to analyze CFAE. MethodsCFAE from several atrial sites, recorded for a duration of 16 s, were acquired from 10 patients with persistent and 9 patients with paroxysmal AF. These signals were appraised using non-overlapping windows of 1-, 2- and 4-s durations. The resulting data sets were analyzed with Recurrence Plots (RP) and Recurrence Quantification Analysis (RQA). The data was also quantified via entropy measures. ResultsRQA exhibited unique plots for persistent versus paroxysmal AF. Similar patterns were observed to be repeated throughout the RPs. Trends were consistent for signal segments of 1 and 2 s as well as 4 s in duration. This was suggestive that the underlying signal generation process is also repetitive, and that repetitiveness can be detected even in 1-s sequences. The results also showed that most entropy metrics exhibited higher measurement values (closer to equilibrium) for persistent AF data. It was also found that Determinism (DET), Trapping Time (TT), and Modified Multiscale Entropy (MMSE), extracted from signals that were acquired from locations at the posterior atrial free wall, are highly discriminative of persistent versus paroxysmal AF data. ConclusionsShort data sequences are sufficient to provide information to discern persistent versus paroxysmal AF data with a significant difference, and can be useful to detect repeating patterns of atrial activation.

Electrochemical analysis of 8-hydroxy-2′-deoxyguanosine with enhanced sensitivity based on exonuclease-mediated functional nucleic acid

In this work, an electrochemical method for sensitive analysis of 8-hydroxy-2′-deoxyguanosine, a key biomarker that is widely used to study oxidative injury-related diseases, is proposed based on exonuclease-mediated functional nucleic acid. In the design, exonuclease can not only distinguish the existence of target, but also suppress the background noise, thus the sensitivity can be enhanced. Moreover, DNAzyme designed in the functional nucleic acid can further improve the sensitivity of the analysis during signal generation process. Therefore, exonuclease-mediated functional nucleic acid may ensure high sensitivity of the assay. Further studies reveal that the detection of 8-hydroxy-2′-deoxyguanosine can be achieved with a linearity from 0.01 nM to 7.0 μM and a detection limit of 6.82 pM. The new method has also been successfully applied to the determination of 8-OHdG in urine with good results, indicating its great potential for practical use.

Finding Value in Momentum

The paper applies momentum-based investment strategies, such as trend and reversal, on government bond futures. It thereby introduces an innovative yet simple approach to harvest time horizon diversification in the signal generation process. Signal diversification over multiple lookback windows enhances returns, independent of the signal aggregation algorithm (naive diversification, maximum diversification, average correlation, Ward distance, equal risk contribution, or principal component analysis). The paper builds two distinct strategies from the same aggregated input signals. The first, time-series momentum (TSMOM), uses time-series aggregation and the second, cross-sectional momentum reversal (XSREV), is calculated in a cross-sectional framework. Specifically, XSREV grounds on government bond pairs, an approach that has a longstanding history within the fixed income space. The paper states that government bond returns are highly correlated and driven by common global factors, which suggests that a reversal strategy is more suitable. Further analysis reveals that XSREV captures a cross-sectional value return factor. With its formulation of XSREV, the paper fills a void in the literature, as existing value measures in fixed income suffer from data quality issues.

Application of linear frequency modulated laser ultrasonic radar in reflective thickness and defect non-destructive testing

Radar technology plays an important role in modern aviation and navigation. Radar systems use pulse-compression and match-filtering to detect large moving objects in the sky or in water, or small defects hidden inside industrial components, the object of this paper. We introduce a nondestructive testing (NDT) modality based on frequency-domain laser ultrasound (FDLU) by means of implementing radar principles: Linear-frequency-modulated (LFM chirp) excitation CW laser-beam intensity to perform, ultrasonic signal cross-correlation with the reference signal using pulse-compression and match-filtering, leading to reconstruction of time-domain sequences through inverse Fourier transformation at acceptable signal-to-noise ratios. Theoretically, the laser ultrasound radar (LUR) signal was modelled with both one- and three-dimensional thermoelastic equations, a combination of which was used to simultaneously predict the correct location and relative amplitude of experimental targets with relatively simple mathematical expressions that could not be used either in the 1-D (too simplistic) or in the 3-D (too complicated) approach alone. This methodology was further used to detect buried defects inside a metal alloy. The results demonstrated that the LUR system is capable of determining the thickness of the alloy material and quantitatively estimate the subsurface depth of defects in a signal generation process akin to echolocation.

Hydrogen-Bond Networks near Supported Lipid Bilayers from Vibrational Sum Frequency Generation Experiments and Atomistic Simulations.

We report vibrational sum frequency generation (SFG) spectra in which the C-H stretches of lipid alkyl tails in fully hydrogenated single- and dual-component supported lipid bilayers are detected along with the O-H stretching continuum above the bilayer. As the salt concentration is increased from ∼10 μM to 0.1 M, the SFG intensities in the O-H stretching region decrease by a factor of 2, consistent with significant absorptive-dispersive mixing between χ(2) and χ(3) contributions to the SFG signal generation process from charged interfaces. A method for estimating the surface potential from the second-order spectral lineshapes (in the OH stretching region) is presented and discussed in the context of choosing truly zero-potential reference states. Aided by atomistic simulations, we find that the strength and orientation distribution of the hydrogen bonds over the purely zwitterionic bilayers are largely invariant between submicromolar and hundreds of millimolar concentrations. However, specific interactions between water molecules and lipid headgroups are observed upon replacing phosphocholine (PC) lipids with negatively charged phosphoglycerol (PG) lipids, which coincides with SFG signal intensity reductions in the 3100-3200 cm-1 frequency region. The atomistic simulations show that this outcome is consistent with a small, albeit statistically significant, decrease in the number of water molecules adjacent to both the lipid phosphate and choline moieties per unit area, supporting the SFG observations. Ultimately, the ability to probe hydrogen-bond networks over lipid bilayers holds the promise of opening paths for understanding, controlling, and predicting specific and nonspecific interactions between membranes and ions, small molecules, peptides, polycations, proteins, and coated and uncoated nanomaterials.

Single-shot pulse duration and intensity diagnostic for 10-ps MeV gamma pulses based on interferometry

To measure the temporal width and the intensity evolution versus time of a MeV gamma pulse generated by a Compton Scatter Source, a time–space conversion method is proposed. This design is based on the consideration that the temporal length of the MeV pulse is proportional to the spatial length of the pulse in a certain semiconductor. The spatial length and the intensity evolution versus time of the MeV pulse can be obtained by recording the region of the refractive index change that is induced by the MeV pulse. The simulation suggests that the equivalent temporal spread of a mono-energy MeV δ pulse in a bulk semiconductor is on the order of picoseconds and does not vary significantly with photon energy and material type. According to our analysis, the excess carrier generation time, excess carrier diffusion and recombination do not significantly influence the temporal resolution of this method. The temporal response of the refractive index change to a MeV pulse is also fast enough to meet the measurement requirements. The signal generation process for measuring a 10-ps MeV pulse with a 200-fs probe beam is analyzed, revealing that the transverse size of the MeV pulse does not influence the temporal resolution of this method.

Numerical Investigation on Electron and Ion Transmission of GEM-based Detectors

ALICE at the LHC is planning a major upgrade of its detector systems, including the TPC, to cope with an increase of the LHC luminosity after 2018. Different R&D activities are currently concentrated on the adoption of the Gas Electron Multiplier (GEM) as the gas amplification stage of the ALICE-TPC upgrade version. The major challenge is to have low ion feedback in the drift volume as well as to ensure a collection of good percentage of primary electrons in the signal generation process. In the present work, Garfield simulation framework has been adopted to numerically estimate the electron transparency and ion backflow fraction of GEM-based detectors. In this process, extensive simulations have been carried out to enrich our understanding of the complex physical processes occurring within single, triple and quadruple GEM detectors. A detailed study has been performed to observe the effect of detector geometry, field configuration and magnetic field on the above mentioned characteristics.

Signal Generation and Verification Process for the Physical Modeling of Ocean Waves

Abstract This paper presents the implementation process of the design methodology for ocean waves in a laboratory tank using a wave generator, which is the basis for conducting hydrodynamic model scale research involving real sea conditions. The main focus is placed on generation of time sequences used as the control input for the wave generator and experimental verification methods for the generated waves and concluding with the results and validation of the developed process by achieving wave parameters sufficiently aligned with the theoretical model.

Risk Aversion, Information Acquisition, and Technology Adoption

We use a dynamic programming model to study the impacts of risk aversion on information acquisition in technology adoption decisions. In this model, the benefit of the technology is uncertain and, in each period, the decision maker (DM) may adopt the technology, reject the technology, or pay to acquire a signal about the benefit of the technology. The dynamic programming state variables are the DM’s wealth and a probability distribution that describes the DM’s beliefs about the benefit of the technology; these distributions are updated over time using Bayes’ rule. If the signal-generating process satisfies the monotone-likelihood ratio property and the DM is risk neutral, the value functions and policies satisfy natural monotonicity properties: a likelihood-ratio improvement in the distribution on benefits leads to an increase in the value function and moves the DM away from rejection and toward adoption. With risk aversion, the value functions (now representing expected utilities) will be monotonic, but the policies need not be monotonic, even with reasonable utility functions. However, if we assume the DM exhibits decreasing absolute risk aversion and is not “too risk averse,” the policies can be shown to be monotonic. Establishing these structural properties requires the use of some novel proof techniques that may prove useful in other contexts. We also study the impact of changing risk attitudes on the optimal policy.The online appendix is available at https://doi.org/10.1287/opre.2017.1601 .

Comparison of perfusion signal acquired by arterial spin labeling–prepared intravoxel incoherent motion (IVIM) MRI and conventional IVIM MRI to unravel the origin of the IVIM signal

Applications of intravoxel incoherent motion (IVIM) imaging in the brain are scarce, whereas it has been successfully applied in other organs with promising results. To better understand the cerebral IVIM signal, the diffusion properties of the arterial blood flow within different parts of the cerebral vascular tree (i.e., different generations of the branching pattern) were isolated and measured by employing an arterial spin labeling (ASL) preparation module before an IVIM readout. ASL preparation was achieved by T1 -adjusted time-encoded pseudo-continuous ASL (te-pCASL). The IVIM readout module was achieved by introducing bipolar gradients immediately after the excitation pulse. The results of ASL-IVIM were compared with those of conventional IVIM to improve our understanding of the signal generation process of IVIM. The pseudo-diffusion coefficient D* as calculated from ASL-IVIM data was found to decrease exponentially for postlabeling delays (PLDs) between 883 ms and 2176 ms, becoming relatively stable for PLDs longer than 2176 ms. The fast compartment of the conventional IVIM-experiment shows comparable apparent diffusion values to the ASL signal with PLDs between 1747 ms and 2176 ms. At the longest PLDs, the observed D* values (4.0 ± 2.8 × 10-3 mm2 /s) are approximately 4.5 times higher than the slow compartment (0.90 ± 0.05 × 10-3 mm2 /s) of the conventional IVIM experiment. This study showed much more complicated diffusion properties of vascular signal than the conventionally assumed single D* of the perfusion compartment in the two-compartment model of IVIM (biexponential behavior). Magn Reson Med 79:723-729, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simulation of the GEM detector for BM@N experiment

The Gas Electron Multiplier (GEM) detector is one of the basic parts of the BM@N experiment included in the NICA project. The simulation model that takes into account features of signal generation process in an ionization GEM chamber is presented in this article. Proper parameters for the simulation were extracted from data retrieved with the help of Garfield++ (a toolkit for the detailed simulation of particle detectors). Due to this, we are able to generate clusters in layers of the micro-strip readout that correspond to clusters retrieved from a real physics experiment.

Performance monitoring by managerial teams

Purpose This paper aims to explore the design of management teams when the critical task facing individual managers is monitoring the performance of worker teams and producing performance measures under uncertain information environments. Design/methodology/approach The authors use a multi-agent LEN framework – linear contract, exponential utility and normal density – to model the incentive provision and organizational design. Findings The main lesson is that the use of performance measures under uncertainty is greatly affected by the potential for free-riding in the very monitoring activities which generate the measures to begin with. Accordingly, the value of having a management team, that is the incremental benefit of having a second manager, depends on the monitoring technology. Of particular importance are the potential free-riding in monitoring effort among multiple managers and synergies gained from having more than one manager, such as correlation among the performance measures produced or improvement due to splitting workers pool into separate groups for each manager to monitor separately. Originality/value The paper pushes this line of research further by explicitly modeling the endogenous process of signal generation within a rich economic environment. In this environment, number of workers being evaluated and number of managers who produce the signals are both endogenous. Furthermore, both workers and managers are subject to moral hazard problem. In particular, the managers suffer from potential free-riding problems but may benefit from synergistic forces due to team monitoring.

Exploring the potential of tailored spectral focusing

We introduce an advanced and flexible spectral focusing coherent anti-Stokes Raman scattering (CARS) microspectroscopy scheme based on the independent control of pump, Stokes, and probe frequencies offered by a pulse shaper. Adjusting the instantaneous bandwidth of 10 fs pulses in the focus of a microscope to different Raman linewidths assures high spectral resolution and signal intensities from the CH-bond to the fingerprint region. Experimental results are confirmed by simulations based on the CARS signal generation process. By delaying the probe, increased signal intensity and minimized nonresonant background are achieved while enabling time-dependent measurements. Contrast based on the difference of decoherence times is established and used to distinguish initially overlapping CH resonances of sunflower oil. Because of the transform-limited nature of the tailored probe, enhanced instantaneous nonlinear signals enable simultaneous multimodal imaging and molecule-specific CARS contrast as demonstrated on human skin tissue.

Research on MeV pulsed radiation detection based on refractive index modulaiton

High time resolution detecting systems for MeV pulsed radiation are essential for inertial confinement fusion diagnostics. Traditional detection of system time resolution is restricted by cable bandwidth. Based on recording excess carrier dynamics in semiconductors, a new detecting mechanism, called RadOptic, was developed by Lawrence Livermore National Laboratory (LLNL). The variation of intensity of pulsed radiation with time was converted into the variation of intensity of infrared laser probe by using this mechanism. The sensing material was InGaAsP quantum wells with severalmicrometer thickness. Picosecond time resolution for several keV pulsed radiation has been demonstrated. The reported system is not suitable for MeV pulses due to its low efficiency to MeV photons. Multiple cascaded structure for MeV photon to electron transformation was proposed by LLNL. Applying bulk material with several-hundredmicrometer thickness is an alternative. Based on transient free carrier absorption, a system recording bulk materials' instantaneous refractive index change is established. The system consists of a probe laser, an interferometer module, a signal transmission module and a signal recording module. The probe is a tunable infrared continuous wave laser whose wavelength is ~1453 nm, guided by single mode fiber to the interferometer. The interferometer consists of a single mode fiber head coupled directly with the polished face of a bulk semiconductor. The interference pattern forms by multiple beams reflected from the front face and the back face of the bulk. Part of interference light is coupled to the single mode fiber and forms the output signal. Pulsed radiation will deposit energy and generate excess carriers in the bulk material. The refractive index of the bulk material changes therewith according to the Drude model. The interference pattern and the light coupled to the single mode fiber also change therewith. The signal is transmitted by a long single mode fiber. The signal recording module consists of photoelectric detectors and a digital oscilloscope. The signal generation process and the time resolution of the system are analyzed. Intrinsic GaAs refractive index change is exploited under electron pulses and X ray pulses. The analysis of signal generation process shows that when the excess carriers recombine much faster/much slower than the pulse width, the output signal/output signal differential can be viewed as a measure of intensity variation with time of the incident pulse. For this prototype system, the time resolution is restricted by the digital oscilloscope to 1 GHz. Bulk intrinsic GaAs demonstrates 30 ns refractive index response time, which is longer than the incident pulse width. The differential signal can be viewed as a measure of incident pulse intensity when GaAs is exposed to 1 ns~0.2 MeV electrons pulses. The differential signal width is shorter than the pulse width when GaAs is exposed to 5 ns~0.2 MeV electrons pulses. Auger recombination process may occur in the pulse duration under this situation. The differential signal width is longer than the pulse width when GaAs is exposed to 1 ns~0.2 MeV X ray pulses. The poor signal to noise ratio affects the signal. The excess carrier generation process may be longer than theoretically estimated one under X ray pulse incident situation. The generation process and recombination process of excess carriers in GaAs show very different characteristics compared with optical excitation. The relationship between the system output signal and the incident pulsed radiation depends on the type of the incident radiation. With carefully considering the effects from incident pulse type and transient carriers density, the system can be used to detect ~MeV pulsed radiation. With an upgraded recording module, the system would demonstrate much higher time resolution.

Theoretical detection threshold of the proton-acoustic range verification technique.

Range verification in proton therapy using the proton-acoustic signal induced in the Bragg peak was investigated for typical clinical scenarios. The signal generation and detection processes were simulated in order to determine the signal-to-noise limits. An analytical model was used to calculate the dose distribution and local pressure rise (per proton) for beams of different energy (100 and 160 MeV) and spot widths (1, 5, and 10 mm) in a water phantom. In this method, the acoustic waves propagating from the Bragg peak were generated by the general 3D pressure wave equation implemented using a finite element method. Various beam pulse widths (0.1-10 μs) were simulated by convolving the acoustic waves with Gaussian kernels. A realistic PZT ultrasound transducer (5 cm diameter) was simulated with a Butterworth bandpass filter with consideration of random noise based on a model of thermal noise in the transducer. The signal-to-noise ratio on a per-proton basis was calculated, determining the minimum number of protons required to generate a detectable pulse. The maximum spatial resolution of the proton-acoustic imaging modality was also estimated from the signal spectrum. The calculated noise in the transducer was 12-28 mPa, depending on the transducer central frequency (70-380 kHz). The minimum number of protons detectable by the technique was on the order of 3-30 × 10(6) per pulse, with 30-800 mGy dose per pulse at the Bragg peak. Wider pulses produced signal with lower acoustic frequencies, with 10 μs pulses producing signals with frequency less than 100 kHz. The proton-acoustic process was simulated using a realistic model and the minimal detection limit was established for proton-acoustic range validation. These limits correspond to a best case scenario with a single large detector with no losses and detector thermal noise as the sensitivity limiting factor. Our study indicated practical proton-acoustic range verification may be feasible with approximately 5 × 10(6) protons/pulse and beam current.

Characterization of the photonic generation of phase-coded RF signals based on pulse shaping and frequency-to-time mapping

Photonic generation of arbitrary waveforms based on pulse shaping and frequency-to-time mapping is of great interest since it offers an effective way to generate complex signals with large bandwidth. In this paper, we mathematically study the photonic generation of phase-coded radio frequency (RF) signals based on pulse shaping and frequency-to-time mapping in detail. By mathematically analyzing the process of signal generation and utilizing the less restrictive dispersion requirement, a design criterion for the generation of well-shaped phase-coded RF waveforms is presented, by which we can properly set the spatial light modulator in the pulse shaper and dispersion in the system according to the carrier frequency and modulating frequency of the desired waveform. In addition, the maximum achievable time-bandwidth product of phase-coded RF signals that can be generated is estimated. The theory is verified by numerical and experimental results. The presented results can be used to guide the design of a photonic system for the generation of high-quality phase-coded RF signals.

Colorimetric detection of single nucleotide polymorphisms in the presence of 103-fold excess of a wild-type gene

Herein, we proposed a simple colorimetric assay for highly sensitive and specific detection of single nucleotide polymorphisms (SNPs). Briefly, SNP specific capture probes (CPs) were immobilized onto magnetic beads. The hybridization of a target SNP with the CPs and detection probes containing multiple DNAzyme sequences (DNAzyme-DPs) brought the target SNP and the DNAzyme-DPs onto the magnetic beads. Meanwhile, a mismatch-specific CEL II enzyme (Surveyor® nuclease) cleaved the imperfectly hybridized wild-type gene together with all other mismatched sequences off the magnetic beads, leaving only the perfectly matched SNP strands on the magnetic beads. Amplified colorimetric detection was carried out through the DNAzyme-catalyzed oxidation of 3,3’,5,5’-tetramethylbenzidine in the presence of H2O2. The excellent selectivity of Surveyor® nuclease toward all imperfectly-matched DNA duplexes produced an ultrahigh selectivity – one mutant in 1000 copies of the wild-type gene can be detected. In addition, the cumulative nature of the DNAzyme-amplified signal generation process produced a detection limit as low as 0.40fM and a dynamic range from 1.0 to 200fM. The simple protocol and its high sensitivity and selectivity allowed the proposed assay to be used in the detection of SNPs in genomic DNA samples.

Biomimetic photo-actuation: sensing, control and actuation in sun-tracking plants

Although the actuation mechanisms that drive plant movement have been investigated from a biomimetic perspective, few studies have looked at the wider sensing and control systems that regulate this motion. This paper examines photo-actuation—actuation induced by, and controlled with light—through a review of the sun-tracking functions of the Cornish Mallow. The sun-tracking movement of the Cornish Mallow leaf results from an extraordinarily complex—yet extremely elegant—process of signal perception, generation, filtering and control. Inspired by this process, a concept for a simplified biomimetic analogue of this leaf is proposed: a multifunctional structure employing chemical sensing, signal transmission, and control of composite hydrogel actuators. We present this multifunctional structure, and show that the success of the concept will require improved selection of materials and structural design. This device has application in the solar-tracking of photovoltaic panels for increased energy yield. More broadly it is envisaged that the concept of chemical sensing and control can be expanded beyond photo-actuation to many other stimuli, resulting in new classes of robust solid-state devices.