Time-dependent Signal Research Articles

Wake characteristics of a sphere performing transverse rotary oscillations

Abstract Three-dimensional computations have been carried out to investigate flow past a sphere performing rotation and rotary oscillation about streamwise axis. The effect of streamwise rotation has been analysed for fixed Reynolds number of 300, with non-dimensional rotational rate taking values 0, 0.5, 1, 1.5 and 2. The transitions in the near wake have been depicted with the help of time-averaged path lines, iso- λ 2 surfaces and vortex core transformation. This study is further extended by considering forced rotational oscillations of the sphere for two different amplitudes of oscillation and reduced oscillation frequency ranging from 0.5 to 2. Effect of these parameters on flow structure has been described using λ 2 -surfaces and streamlines at different locations in the flow field. The response of mean hydrodynamic forces to variation in amplitude and frequency of oscillation has also been reported. Temporal behaviour of wake has been disclosed through Hilbert spectral analysis of time dependent force coefficient signals. The growth and evolution of wake nonlinearities have been elaborated with the help of marginal spectra, Hilbert spectra and distribution of non-stationarity.

Wake characteristics of a sphere performing streamwise rotary oscillations

Three-dimensional computations have been carried out to investigate flow past a sphere performing rotation and rotary oscillation about streamwise axis. The effect of streamwise rotation has been analysed for fixed Reynolds number of 300, with non-dimensional rotational rate taking values 0, 0.5, 1, 1.5 and 2. The transitions in the near wake have been depicted with the help of time-averaged path lines, iso-λ2 surfaces and vortex core transformation. This study is further extended by considering forced rotational oscillations of the sphere for two different amplitudes of oscillation and reduced oscillation frequency ranging from 0.5 to 2. Effect of these parameters on flow structure has been described using λ2-surfaces and streamlines at different locations in the flow field. The response of mean hydrodynamic forces to variation in amplitude and frequency of oscillation has also been reported. Temporal behaviour of wake has been disclosed through Hilbert spectral analysis of time dependent force coefficient signals. The growth and evolution of wake nonlinearities have been elaborated with the help of marginal spectra, Hilbert spectra and distribution of non-stationarity.

The Development of Quasi-isothermal Calorimetry for the Measurement of Drug-Polymer Miscibility and Crystallization Kinetics: Olanzapine-Loaded PLGA Microparticles.

The assessment of drug-polymer equilibrium solubility is of critical importance for predicting suitable loading and physical stability of solid dispersion formulations. However, quantitative measurement of this parameter is nontrivial due to the difficulties associated with ascertaining equilibrium values in systems that are prone to supersaturation and are simultaneously highly viscous, thereby slowing the equilibration process considerably; no standard methodology has yet been agreed for such measurements. In this study, we propose a new approach involving quasi-isothermal modulated temperature DSC (QiMTDSC), whereby unsaturated and supersaturated samples are held at defined temperatures and subject to a sinusoidal heating signal at a zero underpinning heating rate, thereby allowing the heat capacity of the sample to be measured as a function of time and temperature. We are not only able to ascertain whether equilibrium has been reached by monitoring the time-dependent heat capacity signal, but we can also measure solubility as a function of temperature via the absolute heat capacity values of the components. We are also able to measure the kinetics of recrystallization from the supersaturated systems. Dispersions of olanzapine in PLGA at concentrations up to 50% w/w, prepared by spray drying, were prepared and characterized using conventional and QiMTDSC as well as hot stage microscopy. The new QiMTDSC protocol was successfully able to determine olanzapine solubility in PLGA at 90 °C to be 23.1 ± 6.1% w/w, which was comparable to the values calculated using other established methods at this temperature, while a temperature/solubility profile was obtained using the method at a range of temperatures. Drug crystallization kinetics from the solid dispersions could also be modeled directly from the QiMTDSC data using the Avrami approach, thereby allowing the effect of drug loading on the rate of crystallization and the effective completion of crystallization to be investigated. Overall, an alternative protocol for measuring drug-polymer solubility has been developed and validated via comparison to established methods, the approach allowing solubility as a function of temperature, identification of equilibrium following demixing, and kinetic analysis of crystallization to be performed within one set of experiments.

Photonic machine learning implementation for signal recovery in optical communications

Machine learning techniques have proven very efficient in assorted classification tasks. Nevertheless, processing time-dependent high-speed signals can turn into an extremely challenging task, especially when these signals have been nonlinearly distorted. Recently, analogue hardware concepts using nonlinear transient responses have been gaining significant interest for fast information processing. Here, we introduce a simplified photonic reservoir computing scheme for data classification of severely distorted optical communication signals after extended fibre transmission. To this end, we convert the direct bit detection process into a pattern recognition problem. Using an experimental implementation of our photonic reservoir computer, we demonstrate an improvement in bit-error-rate by two orders of magnitude, compared to directly classifying the transmitted signal. This improvement corresponds to an extension of the communication range by over 75%. While we do not yet reach full real-time post-processing at telecom rates, we discuss how future designs might close the gap.

Identification of gene regulation models from single-cell data

In quantitative analyses of biological processes, one may use many different scales of models (e.g. spatial or non-spatial, deterministic or stochastic, time-varying or at steady-state) or many different approaches to match models to experimental data (e.g. model fitting or parameter uncertainty/sloppiness quantification with different experiment designs). These different analyses can lead to surprisingly different results, even when applied to the same data and the same model. We use a simplified gene regulation model to illustrate many of these concerns, especially for ODE analyses of deterministic processes, chemical master equation and finite state projection analyses of heterogeneous processes, and stochastic simulations. For each analysis, we employ Matlab and Python software to consider a time-dependent input signal (e.g. a kinase nuclear translocation) and several model hypotheses, along with simulated single-cell data. We illustrate different approaches (e.g. deterministic and stochastic) to identify the mechanisms and parameters of the same model from the same simulated data. For each approach, we explore how uncertainty in parameter space varies with respect to the chosen analysis approach or specific experiment design. We conclude with a discussion of how our simulated results relate to the integration of experimental and computational investigations to explore signal-activated gene expression models in yeast (Neuert et al 2013 Science 339 584–7) and human cells (Senecal et al 2014 Cell Rep. 8 75–83).

Spin Seebeck effect and ballistic transport of quasi-acoustic magnons in room-temperature yttrium iron garnet films

We studied the transient behavior of the spin current generated by the longitudinal spin Seebeck effect (LSSE) in a set of platinum-coated yttrium iron garnet (YIG) films of different thicknesses. The LSSE was induced by means of pulsed microwave heating of the Pt layer and the spin currents were measured electrically using the inverse spin Hall effect in the same layer. We demonstrate that the time evolution of the LSSE is determined by the evolution of the thermal gradient triggering the flux of thermal magnons in the vicinity of the YIG/Pt interface. These magnons move ballistically within the YIG film with a constant group velocity, while their number decays exponentially within an effective propagation length. The ballistic flight of the magnons with energies above 20 K is a result of their almost linear dispersion law, similar to that of acoustic phonons. By fitting the time-dependent LSSE signal for different film thicknesses varying by almost an order of magnitude, we found that the effective propagation length is practically independent of the YIG film thickness. We consider this fact as strong support of a ballistic transport scenario—the ballistic propagation of quasi-acoustic magnons in room temperature YIG.

A time-dependent fluorescent biosensor for uracil-DNA glycosylase detection based on the uracil inhibition effect towards archaebacterial DNA polymerases

Uracil-DNA glycosylase (UDG) plays important role in DNA lesion repair. It can remove the uracil lesion in DNA and is involved in multiple biological processes. UDG activity detection methods based on DNA probe are developed fast recently due to its high sensitivity and simplicity. They typically use two strategies: the conformational change or the local environmental change of the DNA probe after UDG cleavage. Here we proposed a new strategy for UDG activity detection, which utilized uracil-containing oligo to inhibit archaebacterial DNA polymerases, and after UDG treatment the archaebacterial DNA polymerases could be activated to generate linear or exponential amplification fluorescent signal. The exponential methods showed a time-dependent signal output and achieved limit of detection of 0.0025 U/mL. More importantly, the feature of time-dependence allowed us to easily modulate the resolution or the dynamic range of our method to meet different demands in various occasions. The strategy was also demonstrated to be highly selective toward DNase and exonucleases and had been applied to detect the UDG activity in cell lysate.

Antibody-free detection of cellular neddylation dynamics of Cullin1

Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay utilizes the NanoLuc® Binary Technology (NanoBiT) to monitor the covalent neddylation status of Cul1. A stable clonal cell line derived from HEK293 was developed that expressed a C-terminus LgBiT tagged-Cul1 and N-terminus SmBiT tagged-Nedd8. Using this cell line, we screened inhibitors that are known to disrupt Nedd8 biology and demonstrated that both inhibitors of Nedd8-activating enzyme (NAE) and Constitutive photomorphogenesis 9 signalosome (CSN) complex produce concentration and time dependent signal decreases and increases, respectively. The kinetics of both responses could be monitored in real time and demonstrated that modulation of the Nedd8 pathway occurs rapidly. Further characterization of the cellular components of this cell line was performed in order to quantify the various levels of Cul1, Nedd8 and NAE and determined to be near endogenous levels. There was no difference between control and stably transfected cell lines in viability studies of NAE and CSN inhibitors. Taken together, these results suggest that the NanoBiT assay can be used to monitor Cul1 neddylation specifically and in real time.

Embedding sensors in composite plates for characterization under impacting shock wave loading

High-frequency-response, semiconductor, strain gages used in various combinations have been embedded in S-2 glass epoxy composite test plates during in-house fabrication using vacuum-assisted resin transfer molding in order to measure the transient strain and its rate during the impingement of the shock wave and subsequent interactions. To validate the techniques systematically, an in-house-developed, split-view time-resolved, stereo digital image correlation system has been used to compare static and time-dependent strain signals on a two-dimensional surface in a shock tube facility. Small size non-encapsulated solid-state gages were cumbersome to handle during the fabrication process, while encapsulated strain gages had very good spatial resolution and overall performance combined with some ease in handling during fabrication. The strain results indicate that embedding sensors is an accurate and inexpensive method to characterize composites under high-rate loading.

Sturmian–Floquet approach to high-order harmonic generation

We show that the Floquet approach with a Sturmian basis means an efficient description of high-order harmonic generation (HHG) with monochromatic excitation. This method, although it involves numerical calculations, is close to analytic approaches with a corresponding deeper insight into the dynamics. As a first application, we investigate the role of atomic coherence during the process of HHG: as shown, different coherent superpositions of initial atomic states produce observably different HHG spectra. For linearly polarized excitation, we demonstrate that the question whether the constituents of the initial superpositions are dipole coupled or not strongly influences the dynamics. By investigating time-dependent HHG signals, we also show that the preparation of the initial atomic state can be used for the control of the high-harmonic radiation.

Dynamic in-process characterization method based on acoustic emission for topographic assessment of conventional grinding wheels

The main goal of the present research is to evaluate an acoustic emission (AE)-based quick test-method for in-process determination of the topographic characteristics of a fused aluminum oxide grinding wheel. The in-process evaluation is carried out by scanning the effective width of the grinding wheel with an instrumented diamond tip under interferences in the realm of the elastic deformation range. These contact interferences generate broad frequency AE signals, which are detected by an AE transducer and converted into a proportional electric tension as a time-dependent raw signal, AERAW. The AERAW signals are simultaneously transferred to the employed hardware for online conditioning and signal sampling. A software has been developed to extract in-process quantified information from the sampled AERAW signals. The obtained quantitative information is based on both time and frequency domain analyses, resulting in fast extraction of in-process information related to the grinding wheel topography without stopping the grinding process for post-analyses. The presented method permits obtaining the information of the grinding wheel topography at usual cutting speeds. The validation of the proposed AE-based quick-test method is accomplished through a post-process evaluation of both the grinding cutting force components and the effective roughness of the grinding wheel.

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry.

Sensitivity of detection is one of the most limiting aspects when applying NMR spectroscopy to current problems in the molecular sciences. A number of hyperpolarization methods exist for increasing the population difference between nuclear spin Zeeman states and enhance the signal-to-noise ratio by orders of magnitude. Among these methods, dissolution dynamic nuclear polarization (D-DNP) is unique in its capability of providing high spin polarization for many types of molecules in the liquid state. Originally proposed for biomedical applications including in vivo imaging, applications in high resolution NMR spectroscopy are now emerging. These applications are the focus of the present review. Using D-DNP, a small sample aliquot is first hyperpolarized as a frozen solid at low temperature, followed by dissolution into the liquid state. D-DNP extends the capabilities of liquid state NMR spectroscopy towards shorter timescales and enables the study of nonequilibrium processes, such as the kinetics and mechanisms of reactions. It allows the determination of intermolecular interactions, in particular based on spin relaxation parameters. At the same time, a challenge in the application of this hyperpolarization method is that spin polarization is nonrenewable. Substantial effort has been devoted to develop methods for enabling rapid correlation spectroscopy, the measurement of time-dependent signals, and the extension of the observable time window. With these methods, D-DNP has the potential to open new application areas in the chemical and biochemical sciences.

Exploring Nuclear Photorelaxation of Pyranine in Aqueous Solution: an Integrated Ab-Initio Molecular Dynamics and Time Resolved Vibrational Analysis Approach.

Advances in time-resolved vibrational spectroscopy techniques provided a new stimulus for understanding the transient molecular dynamics triggered by the electronic excitation. The detailed interpretation of such time-dependent spectroscopic signals is a challenging task from both experimental and theoretical points of view. We simulated and analyzed the transient photorelaxation of the pyranine photoacid in aqueous solution, with special focus on structural parameters and low frequency skeleton modes that are possibly preparatory for the photoreaction occurring at later time, as suggested by experimental spectroscopic studies. To this aim, we adopted an accurate computational protocol that combines excited state ab initio molecular dynamics within an hybrid quantum mechanical/molecular mechanics framework and a time-resolved vibrational analysis based on the Wavelet transform. According to our results, the main nuclear relaxation on the excited potential energy surface is completed in about 500 fs, in agreement with experimental data. The rearrangement of C-C bonds occurs according to a complex vibrational dynamics, showing oscillatory patterns that are out of phase and modulated by modes below 200 cm-1. We also analyzed in both the ground and the excited state the evolution of some structural parameters involved in excited state proton transfer reaction, namely, those involving the pyranine and the water molecule hydrogen bonded to the phenolic O-H group. Both the hydrogen bond distance and the intermolecular orientation are optimized in the excited state, resulting in a tighter proton donor-acceptor couple. Indeed, we found evidence that collective low frequency skeleton modes, such as the out of plane wagging at 108 cm-1 and the deformation at 280 cm-1, are photoactivated by the ultrafast part of the relaxation and modulate the pyranine-water molecule rearrangement, favoring the preparatory step for the photoreactivity.

Selective Orientation of Chiral Molecules by Laser Fields with Twisted Polarization.

We explore a pure optical method for enantioselective orientation of chiral molecules by means of laser fields with twisted polarization. Several field implementations are considered, including a pair of delayed, cross-polarized laser pulses, an optical centrifuge, and polarization-shaped pulses. We show that these schemes lead to out-of-phase time-dependent dipole signals for different enantiomers, and we also predict a substantial permanent molecular orientation persisting long after the laser fields are over. The underlying classical orientation mechanism common to all of these fields is discussed, and its operation is demonstrated for a range of chiral molecules of various complexity: hydrogen thioperoxide (HSOH), propylene oxide (CH3CHCH2O), and ethyl oxirane (CH3CH2CHCH2O). The presented results demonstrate generality, versatility, and robustness of this optical method for manipulating molecular enantiomers in the gas phase.

Microstructure Characterization of Bone Metastases from Prostate Cancer with Diffusion MRI: Preliminary Findings.

To examine the usefulness of rich diffusion protocols with high b-values and varying diffusion time for probing microstructure in bone metastases. Analysis techniques including biophysical and mathematical models were compared with the clinical apparent diffusion coefficient (ADC). Four patients were scanned using 13 b-values up to 3,000 s/mm2 and diffusion times ranging 18-52 ms. Data were fitted to mono-exponential ADC, intravoxel incoherent motion (IVIM), Kurtosis and Vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) models. Parameters from the models were compared using correlation plots. ADC and IVIM did not fit the data well, failing to capture the signal at high b-values. The Kurtosis model best explained the data in many voxels, but in voxels exhibiting a more time-dependent signal, the VERDICT model explained the data best. The ADC correlated significantly (p < 0.004) with the intracellular diffusion coefficient (r = 0.48), intracellular volume fraction (r = -0.21), and perfusion fraction (r = 0.46) parameters from VERDICT, suggesting that these factors all contribute to ADC contrast. The mean kurtosis correlated with the intracellular volume fraction parameter (r = 0.26) from VERDICT, consistent with the hypothesis that kurtosis relates to cellularity, but also correlated weakly with the intracellular diffusion coefficient (r = 0.18) and cell radius (r = 0.16) parameters, suggesting that it may be difficult to attribute physical meaning to kurtosis. Both Kurtosis and VERDICT explained the diffusion signal better than ADC and IVIM, primarily due to poor fitting at high b-values in the latter two models. The Kurtosis and VERDICT models captured information at high b using parameters (Kurtosis or intracellular volume fraction and radius) that do not have a simple relationship with ADC and that may provide additional microstructural information in bone metastases.

Transient SHG Imaging on Ultrafast Carrier Dynamics of MoS2 Nanosheets

Understanding the collaborative behaviors of the excitons and phonons that result from light-matter interactions is important for interpreting and optimizing the underlying fundamental physics at work in devices made from atomically thin materials. In this study, the generation of exciton-coupled phonon vibration from molybdenum disulfide (MoS2 ) nanosheets in a pre-excitonic resonance condition is reported. A strong rise-to-decay profile for the transient second-harmonic generation (TSHG) of the probe pulse is achieved by applying substantial (20%) beam polarization normal to the nanosheet plane, and tuning the wavelength of the pump beam to the absorption of the A-exciton. The time-dependent TSHG signals clearly exhibit acoustic phonon generation at vibration modes below 10 cm-1 (close to the Γ point) after the photoinduced energy is transferred from exciton to phonon in a nonradiative fashion. Interestingly, by observing the TSHG signal oscillation period from MoS2 samples of varying thicknesses, the speed of the supersonic waves generated in the out-of-plane direction (Mach 8.6) is generated. Additionally, TSHG microscopy reveals critical information about the phase and amplitude of the acoustic phonons from different edge chiralities (armchair and zigzag) of the MoS2 monolayers. This suggests that the technique could be used more broadly to study ultrafast physics and chemistry in low-dimensional materials and their hybrids with ultrahigh fidelity.

Separating fast and slow exchange transfer and magnetization transfer using off‐resonance variable‐delay multiple‐pulse (VDMP) MRI

To develop a method that can separate and quantify the fast (>1 kHz) and slow exchange transfer and magnetization transfer components in Z-spectra. Z-spectra were recorded as a function of mixing time using a train of selective pulses providing variable-delay multipulse build-up curves. Fast and slow transfer components in the Z-spectra were separated and quantified on a voxel-by-voxel basis by fitting the mixing time-dependent CEST signal using a 3-pool model. Phantom studies of glutamate solution, bovine serum albumin solution, and hair conditioner showed the capability of the proposed method to separate fast and slow transfer components. In vivo mouse brain studies showed a strong contrast between white matter and gray matter in the slow-transferring map, corresponding to an asymmetric component of the conventional semisolid magnetization transfer contrast. In addition, a fast-transferring proton map was found that was homogeneous across the brain and attributed to the total contributions of the fast-exchanging protons from proteins, metabolites, and a symmetric magnetization transfer contrast component. This new method provides a simple way to extract fast and slow transfer components from the Z-spectrum, leading to novel MRI contrasts, and providing insight into the different magnetization transfer contrast contributions.

Frequency-Modulated Continuous Flow Analysis Electrospray Ionization Mass Spectrometry (FM-CFA-ESI-MS) for Sample Multiplexing.

A method for multiplexed sample analysis by mass spectrometry without the need for chemical tagging is presented. In this new method, each sample is pulsed at unique frequencies, mixed, and delivered to the mass spectrometer while maintaining a constant total flow rate. Reconstructed ion currents are then a time-dependent signal consisting of the sum of the ion currents from the various samples. Spectral deconvolution of each reconstructed ion current reveals the identity of each sample, encoded by its unique frequency, and its concentration encoded by the peak height in the frequency domain. This technique is different from other approaches that have been described, which have used modulation techniques to increase the signal-to-noise ratio of a single sample. As proof of concept of this new method, two samples containing up to 9 analytes were multiplexed. The linear dynamic range of the calibration curve was increased with extended acquisition times of the experiment and longer oscillation periods of the samples. Because of the combination of the samples, salt had little effect on the ability of this method to achieve relative quantitation. Continued development of this method is expected to allow for increased numbers of samples that can be multiplexed.

Transit-time and age distributions for nonlinear time-dependent compartmental systems

Many processes in nature are modeled using compartmental systems (reservoir/pool/box systems). Usually, they are expressed as a set of first-order differential equations describing the transfer of matter across a network of compartments. The concepts of age of matter in compartments and the time required for particles to transit the system are important diagnostics of these models with applications to a wide range of scientific questions. Until now, explicit formulas for transit-time and age distributions of nonlinear time-dependent compartmental systems were not available. We compute densities for these types of systems under the assumption of well-mixed compartments. Assuming that a solution of the nonlinear system is available at least numerically, we show how to construct a linear time-dependent system with the same solution trajectory. We demonstrate how to exploit this solution to compute transit-time and age distributions in dependence on given start values and initial age distributions. Furthermore, we derive equations for the time evolution of quantiles and moments of the age distributions. Our results generalize available density formulas for the linear time-independent case and mean-age formulas for the linear time-dependent case. As an example, we apply our formulas to a nonlinear and a linear version of a simple global carbon cycle model driven by a time-dependent input signal which represents fossil fuel additions. We derive time-dependent age distributions for all compartments and calculate the time it takes to remove fossil carbon in a business-as-usual scenario.

Tracking Control via Variable-gain Integrator and Lookahead Simulation: Application to Leader-follower Multiagent Networks

This paper concerns an output-tracking technique based on a standalone integrator with variable gain. The control algorithm, recently proposed by the authors, appears to have a wide scope in linear and nonlinear systems while aiming at simple and efficient computations in the loop. For a class of memoryless systems it resembles a Newton-Raphson flow for solving the loop equation, but it is applicable to a broader class of dynamical systems. Furthermore, the technique is suitable for tracking constant as well as time-dependent reference signals, and its convergence performance is robust with respect to computational errors in the loop. The objective of this paper is to test the technique on a control problem arising in multi-agent systems. Specifically, we are motivated by regulating trajectories of follower agents by a lead agent in a platoon or swarm of multi-agent networks connected by the graph Laplacian. We study a particular example, which is challenging from the standpoint of control, with the aim of identifying the limits of the technique and investigating their possible extensions.