Binary Pulse Research Articles

Abstract A021: Evolutionary immunotherapy in NSCLC: An integrated approach

Abstract Purpose: Our study examines tumor growth dynamics and immunosuppression under the presence of immune attack to identify optimal immune pulsing treatment strategies. Motivation: Checkpoint inhibitors disrupting the PD-1/PD-L1 axis are used in multiple cancer subtypes. However, not all patients respond, and predictive biomarkers are needed to better stratify patients. Therapy for PD-L1, the most studied biomarker, has given mixed results in non-small cell lung cancer (NSCLC). The complexity of the immune response and plastic nature of PD-L1/PD-1 expression on tumor and immune cells contributes to the heterogeneity of success. IFN-γ, a cytokine released by activated immune cells, induces PD-L1 expression in some tumor cells. Chronic IFN-γ results in long-term PD-L1 expression. However, relaxation dynamics following removal of IFN-γ remains unexplored. In this study, we investigate these complex PD-L1 dynamics through a unique combination of in vitro studies and mathematical modeling. METHODS: In vitro experimental data: We have collected in vitro and temporal confocal microscopy images of PD-L1 expression on NSCLC cells, which were either untreated or treated for 48 hours with high dose IFN-γ followed by chronic low dose IFN-γ for 21 days.Agent-based model: To reinforce our in vitro experiments and findings, we developed a hybrid agent-based model (ABM) to study PD-L1 dynamics. The agents in the ABM are tumor cells having variable PD-L1 expression, and immune cells that secrete IFN-γ. Tumor cells can be randomly seeded or seeded as a cluster of cells. IFN-γ is modeled as either a binary well-mixed pulse (to simulate the in vitro experimental setup), or as a diffusible via a reaction-diffusion process (to simulate the tumor-immune cell interactions in an in-vivo spatial manner). This allows us to investigate the effects of various pulsing strategies of immunotherapy on tumor evolution where each pulse can be a variable dose of immune cells, given at regular or irregular intervals. RESULTS: Our in vitro experimental data and microscopy images confirm that PD-L1 expression continues to increase within the cells after a 48-hour IFN-γ exposure followed by low levels of IFN-γ. Our ABM has been calibrated to capture in vitro data dynamics for different conditions. Our initial results indicate that pulsing immunotherapy may lead to better overall immune efficacy than continuous immunotherapy, by preventing sustained suppression that increases immune cell exhaustion, despite the potential for tumor regrowth between pulses. We also hypothesize that pulsing immunotherapy will have different immunosuppression effects when tumors are clustered or randomly distributed. CONCLUSION: We have quantified the temporal dynamics of PD-L1 expression in NSCLC cells under different conditions of IFN-γ, and built an ABM to study tumor-immune evolution under various pulsing strategies. The results of this work could lead to improved therapy schedules in patients responsive to checkpoint inhibitors that exploit the complex dynamics of immune response and suppression. Citation Format: Sandhya Prabhakaran, Taylor M. Bursell, Kimberly Luddy, Julian Pineiro, Rafael Bravo, Jeffrey West, Megan Johnson, Mark Robertson-Tessi, Amer A. Beg, Jhanelle E. Gray, Scott Antonia, Robert A. Gatenby, Alexander R. A. Anderson. Evolutionary immunotherapy in NSCLC: An integrated approach [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A021.

Influence of the operating regime of the magnonic active ring oscillator on the performance of the magnonic reservoir computer based on it

A magnonic active ring oscillator based on an yttrium iron garnet (YIG) is a promising hardware platform for physical reservoir computing. It meets the required conditions for the availability of fading memory and nonlinearity. However, its performance still needs further improvement. Two methods can be employed to improve the performance. One is increasing the time of establishing steady self-oscillations in the auto-oscillator. The second one is increasing the amplitude of spin waves propagating in the YIG film. In this work, we achieve an increase of the amplitude of the reservoir response by broadening the available range for the ring gain coefficient. We use a metallized YIG film as a waveguide in which spin waves propagate. This shifts up the amplitude threshold for the development of spin wave modulation instability in the ring. The threshold defines the upper limit of the gain range for the ring. Binary pulse sequence is entered into the ring by switching its gain between upper and lower levels. The modulation instability threshold then sets the upper limit for the higher gain level. In addition, in this work, we set the lower level of the gain to negative values. This is one more improvement with respect to earlier works. Switching the gain between a negative and a positive value increases the amplitude of the reservoir response and the depth of its fading memory. We employ the standard short-term memory and parity-check tests to quantify the performance of the reservoir computer. Both tests demonstrate an increase in the computational efficiency of the magnonic reservoir.

Small RCS targets detection based on pulse compression radar signal generator and processor

In the last two decades, field programmable gate arrays (FPGAs) have become the leading technology for implementing real time systems, specially radars. The most important advantage of FPGA is its parallel nature of executing complicated algorithms. As a result, the received data flow will be processed in a real time manner, which is suitable for radar applications. This paper attempts to show the design and the FPGA implementation of a binary phase-coded pulse compression radar signal generator and processor, that are intended to determine the ranges, and the speeds of targets with small radar cross-section area like drones. The system operating waveform is a bi-phase sequence, that is known to have the best known peak sidelobe level compared to compound Barker codes of the same length. In addition, the design incorporates a range sidelobes cancellation method to remove the time sidelobes in the matched filter output. Also, we are going to represent and investigate the FPGA implementing steps of the radar waveform generator and processor according to the required parameters. Finally, the implementation results of the proposed system will be represented.

Characteristics and selection of near-fault simulated earthquake ground motions for nonlinear analysis of buildings

Earthquake-induced ground shaking near rupturing faults is highly sensitive to the rupture characteristics, seismic wave propagation patterns and site conditions, and field recordings of near-fault shaking are relatively sparse. These challenges complicate the assessment of the seismic performance of near-fault structures. A common approach to representing near-fault ground motion in engineering analysis is to explicitly consider and select records with strong directivity pulses (pulse records). We use three-dimensional high-resolution physics-based earthquake simulations to test this approach in the context of scenario-based ground motion record selection, and to study the important characteristics of near-fault ground shaking. We highlight the deficiencies associated with classifying near-fault simulated records as “pulse” or “non-pulse,” based on the presence of a single dominating pulse in the velocity time history. We show that this approach is inadequate for characterizing near-fault shaking on soft soils which can be dominated by both forward rupture directivity and basin amplification effects. We conduct ground motion selection experiments for the analysis of near-fault structures with and without explicit classification of the pulse features in the records, and evaluate the bias in the predicted structural demands. We find that the maximum interstory drift demands on building structures imposed by unscaled site-specific simulated ground motion records selected based on relevant spectral shape features are not sensitive to the classification of records as pulse/non-pulse. Therefore, with regard to predicting the maximum interstory drifts in near-fault buildings, we do not find justification for the binary pulse classification of near-fault records.

Long-range underwater optical wireless communication systems in turbulent conditions.

In this paper, single-photon avalanche diode (SPAD) photodetectors are leveraged across long-range underwater optical wireless communication (UOWC) systems for non-turbid waters, i.e., pure sea and clear ocean, in weak turbulent conditions. We derive the bit error probability of the system using on-off keying (OOK) along with two types of SPADs: ideal, i.e., with zero dead time, and practical, i.e., with non-zero dead time. In our investigations for OOK systems, we study the effect of using both the optimum threshold (OTH) and constant threshold (CTH) at the receiver. Furthermore, we analyze the performance of systems using binary pulse position modulation (B-PPM) and compare them with the ones using OOK. Our results are presented for practical SPADs and both active and passive quenching circuits. We demonstrate that OOK systems with OTH perform slightly better than B-PPM. However, our investigations reveal that in turbulent conditions where using OTH may be challenging, employing B-PPM can be preferable to OOK.

Binary Control Pulse Optimization for Quantum Systems

Quantum control aims to manipulate quantum systems toward specific quantum states or desired operations. Designing highly accurate and effective control steps is vitally important to various quantum applications, including energy minimization and circuit compilation. In this paper we focus on discrete binary quantum control problems and apply different optimization algorithms and techniques to improve computational efficiency and solution quality. Specifically, we develop a generic model and extend it in several ways. We introduce a squared L2-penalty function to handle additional side constraints, to model requirements such as allowing at most one control to be active. We introduce a total variation (TV) regularizer to reduce the number of switches in the control. We modify the popular gradient ascent pulse engineering (GRAPE) algorithm, develop a new alternating direction method of multipliers (ADMM) algorithm to solve the continuous relaxation of the penalized model, and then apply rounding techniques to obtain binary control solutions. We propose a modified trust-region method to further improve the solutions. Our algorithms can obtain high-quality control results, as demonstrated by numerical studies on diverse quantum control examples.

Inducing the structural interplay of binary pulse protein complex to stimulate the solubilization of chickpea (Cicer arietinum L.) protein isolate

Chickpea protein (CP) is an exceptional nutrient-dense pulse protein prevailing in the development of plant-based foods. However, its relatively low solubility, compared to other legume proteins, hinders the practical uses of CP in food matrix. To resolve this problem, pea protein (PP), another popular pulse protein, was co-assembled with CP to form a binary complex during the alkaline pH-shifting process. Results indicated that the complexed CP exhibited significantly increased solubility to that of the pristine protein (more than 50%), whose aqueous stability was also enhanced against different environmental stresses (pH, salt, heat/frozen treatment, and centrifugation). Structural and morphology analysis confirmed the interplay between unfolded CP and PP during pH shifting, which enabled their resistance to acid-induced structural over-folding. Our experiments that induce the co-assembling of two pulse proteins provide a novel routine and scientific basis for tailoring CP functionalities, as well as the formulation of pulse protein-based products.

Gray Image Denoising Based on Array Stochastic Resonance and Improved Whale Optimization Algorithm

Aiming at the poor effect of traditional denoising algorithms on image enhancement with strong noise, an image denoising algorithm based on improved whale optimization algorithm and parameter adaptive array stochastic resonance is proposed in the paper. In this algorithm, through dimensionality reduction scanning, coding, modulation and other processing, the noise-containing gray image becomes a one-dimensional aperiodic binary pulse amplitude modulation signal suitable for a bistable stochastic resonance model. Then, the traditional whale optimization algorithm is improved in the initial solution distribution, global search ability and population diversity generalization. The improved whale optimization algorithm is applied to select the parameters of the stochastic resonance, which effectively improves the parameters self-adaptive of the array stochastic resonance model. Finally, the denoised image is obtained by demodulating, decoding and anti-scanning the stochastic resonance output. The experimental results show that compared with the array stochastic resonance method with fixed parameters and the classical image denoising method, the algorithm proposed in this paper has better performance in terms of visual effect and peak signal-to-noise ratio index, which proves the advantages and effective application of the method in image denoising.

Performance Evaluation of Pulse Position Modulation Scheme in Automatic Dependent Surveillance Broadcast System

this paper presents a new formula for calculating the Bit Error Rate (BER) and the Packet Error Rate (PER) for binary pulse position modulation scheme which had been used in Automatic Dependent Surveillance Broadcast (ADS-B) system, ADS-B system is used in air traffic surveillance and control. ADS-B system uses the Binary Pulse Position Modulation (BPPM) scheme in the link between the aircraft and the ground station. The results show that the simulated bit-error rate and packet error rate are approximately matches the theoretical one; these results have been obtained for both coherent and non-coherent detection. As a result, mathematical formulas to represent the probability of error for BPPM are also derived for both coherent and no-coherent detection scheme.

A predictive model of organic acids separation by chromatography with strong anionic resins in sulfate form

Organic acids commonly have quite symmetrical chromatography profiles at low pH (< 1.5) with strong anionic resins, but a significant tailing can be observed with succinic and citric acids. Classical adsorption models, like the Langmuir model, fail to predict this behavior, which can have a major influence on mean retention times and profile shapes, therefore on chromatography performances.A new retention model was developed to better predict organic acid separation with strong anionic resin. This model combines a refined Langmuir adsorption model and an ion-exchange model. Organic acid adsorption is assumed to be due to hydrogen bonding with sulfate and hydrogen sulfate counter-anions on the resin. The adsorption capacity depends mostly on molecular size: up to sixteen formic acid molecules could be adsorbed per counter-anions, meanwhile only two succinic acid or one citric acid molecules could be adsorbed.This adsorption model was then embedded in a generic and accurate modeling approach (continuous column with mass balance equations solved by the conservation element/solution element (CE/SE) method). All parameters of this column model were identified by fitting the simulation to experimental results (equilibrium curves and pulse tests). Then, the column model was validated with original experimental results from a binary mixture pulse test (formic and succinic acids). Results show that simulations are much more predictive for multi-component pulse tests, both in terms of profile shape and retention time, which cannot be captured without considering ion-exchange.

Nonlinear color space coded by additive digital pulses

Additive color mixing modulated by digital pulses enables universal applications in lights and displays. Conventional methods map binarized signals to ordinary red–green–blue color spaces, loosely connected with the color perception of human eyes, causing the complexity of gamut mapping and inaccuracy of chromatic manipulations. Here we developed a complete theory that encodes and decodes digital signals directly to a perceptually nonuniform color space of the commission internationale de l’éclairage, featuring a strict bijection between the duty cycles of each binary pulse and color components of the mixed light and an analytic nonlinear gamut volume. Exemplary applications in biophotonic lighting, active full-color displaying, and metaphotonic sensing confirmed our theory. The method applies to the fields with accurate manipulations of chromaticity and luminosity of a light, opening an avenue toward the next generation of perceptual displays, cameras, and sensors.

Selection on Golay complementary sequences in binary pulse compression for microbubble detection

In medical ultrasound imaging using microbubbles (MBs), the nonlinear echoes from the MBs are used for contrast-specific image construction. Techniques such as pulse inversion, amplitude modulation, and the combined method (PIAM) are employed to increase nonlinear components in the echoes. In addition, employment of pulse compression using binary-coded ultrasound can potentially increase the components. In the case of the nonlinear echo, however, a nonlinear sidelobe occurs around the compressed pulse (correlation peak), and nonlinear components for PIAM in the correlation peak are reduced. The shape of the nonlinear sidelobe and the nonlinear-component reduction in the correlation peak can be estimated from the binary codes used. In this study, the optimal binary codes for PIAM are determined from all patterns of 10, 16, and 20 bit Golay codes. Then, the performance of PIAM with pulse compression using each code is evaluated via computer simulations and experiments using the SonoVue MBs.

Research on Image Signal Identification Based on Adaptive Array Stochastic Resonance

Aiming at the problems of low accuracy of image signal identification and poor anti-noise signal interference ability under strong noise environment, a signal identification method of correlated noisy image based on adaptive array stochastic resonance (SR) is proposed in this paper. Firstly, the two-dimensional grayscale image is transformed to a one-dimensional binary pulse amplitude modulation (BPAM) signal with periodicity by the row or column scanning method, encoding and modulation. Then, the one-dimensional low signal-to-noise ratio BPAM signal can be applied to the saturating nonlinearity array SR module for image signal identification processing and part of the noise energy is converted into signal energy. Finally, the one-dimensional image signal processed by the nonlinearities is demodulated, decoded and reverse scanned to get the restored grayscale image. The simulation results show that the image signal identification method proposed in this paper is highly efficient and accurate for the identification of noisy image signals of different sizes, and the bit error rate (BER) is also significantly reduced.

A Novel Defocused Image Segmentation Method Based on PCNN and LBP

The defocus blur concept adds an artistic effect and enables an enhancement in the visualization of image scenery. Moreover, some specialized computer vision fields, such as object recognition or scene restoration enhancement, might need to perform segmentation to separate the blurred and non-blurred regions in partially blurred images. This study proposes a sharpness measure comprised of a Local Binary Pattern (LBP) descriptor and Pulse Coupled Neural Network (PCNN) component used to implement a robust approach for segmenting in-focus regions from out of focus sections in the scene. The proposed approach is very robust in the sense that the parameters of the model can be modified to accommodate different settings. The presented metric exploits the fact that, in general, local patches of the image in blurry regions have less prominent LBP descriptors than non-blurry regions. The proposed approach combines this sharpness measure with the PCNN algorithm; the images are segmented along with clear regions and edges of segmented objects. The proposed approach has been tested on a dataset comprised of 1000 defocused images with eight state-of-the-art methods. Based on a set of evaluation metrics, i.e., precision, recall, and F1-Measure, the results show that the proposed algorithm outperforms previous works in terms of prominent accuracy and efficiency improvement. The proposed approach also uses other evaluation parameters, i.e., Accuracy, Matthews Correlation Coefficient (MCC), Dice Similarity Coefficient (DSC), and Specificity, to assess better the results obtained by our proposal. Moreover, we adopted a fuzzy logic ranking scheme inspired by the Evaluation Based on Distance from Average Solution (EDAS) technique to interpret the defocus segmentation integrity. The experimental outputs illustrate that the proposed approach outperforms the referenced methods by optimizing the segmentation quality and reducing the computational complexity.

Compact Laser Driver for Ultrasonic Arbitrary Position and Width Pulse Sequences Generation

Laser ultrasound offers several benefits in comparison to immersion or air-coupled ultrasound: it directly generates stress on the sample surface; it has a wide bandwidth and a small acoustic source can be produced. Conventionally, high-power pulsed lasers are required therefore equipment is bulky and expensive. Here we propose to use mid-power laser diodes, which are small and low cost. To solve the low signal amplitude problem with lower power lasers, the use of spread spectrum signal, arbitrary position, and width binary pulse sets is proposed. To date, a laser driver for this task has not been available. This article describes the development of such a compact driver, where the essential electronics occupy an area of $10\,\,\times20$ mm. The whole system with a fixture for kinematic mount is comparable in size to a conventional piezoelectric ultrasonic transducer. The driver can supply pulse sets of up to 40 A. Individual pulse duration can vary between 20 and 1000 ns (0.5–25-MHz ultrasound range) and the total pulse train duration is limited by the laser type used. Experiments show that up to 10- $\mu \text{s}$ long pulse sets can be used at 10-A current, without laser degradation. Current waveforms, beam profile, and optical response signals were measured for three rectified topologies. It was concluded that the GaN-based constant current switch topology has the best performance, but a power MOSFET in a source current feedback topology can also be used to generate pulses down to 20 ns. Photoacoustic response signals from chirp and phase shift keying modulation have been demonstrated.

Image Restoration Based on Stochastic Resonance in a Parallel Array of Fitzhugh–Nagumo Neuron

The poor denoising effect for noisy grayscale images with traditional processing methods would be obtained under strong noise condition, and some image details would be lost. In this paper, a parallel array model of Fitzhugh–Nagumo (FHN) neurons was proposed, which can restore noisy grayscale images well with low peak signal-to-noise ratio (PSNR) conditions and the image details are better preserved. Firstly, the row-column scanning method was used to convert the 2D grayscale image into a 1D signal, and then the 1D signal was converted into a binary pulse amplitude modulation (BPAM) signal by signal modulation. The modulated signal was input to an FHN parallel array for stochastic resonance (SR). Finally, the array output signal was restored to a 2D gray image, and the image restoration effect was analyzed based on the PSNR and Structural SIMilarity (SSIM) index. It is shown that the SR effect can be exhibited in an array of FHN neuron nonlinearities by increasing the array size, and the image restoration effect is significantly better than the traditional image restoration method, and larger PSNR and SSIM can be obtained. It provides a new idea for grayscale image restoration in a low PSNR environment.

System Level Simulation of Energy-Detection Based UWB Receivers

The performance of a non-coherent UWB receiver with Binary pulse position modulation is simulated with MATLAB; taking into account the effect of non-linearity, noise, pulse shape and channel effects. This simulation examines the minimum requirements for LNA, AGC, squarer, and operational transconductance amplifier in analog front-end for sensor network application with 100Kb/s data rate and 10-3 BER. The linearity requirement in OTA is achieved using Gilbert cell OTA with the technique of multiple gated transistors. For sensor network applications, analog front-end modules must have 4dB NF (Noise figure), -12dBm IIP3, 50dB gain and -75dBm sensitivity for 100Kb/s data rates. The transceiver power consumption is assumed to be below 50mW. The performance of energy detection non-coherent receiver is simulated in Simulink of MATLAB, it shows that BER of Gaussian pulse is lower than doublet and 4th Gaussian pulse. By increasing the number of transmitted pulse per bit and IIP3, the performance of receiver is improved.

A comparison of low-complexity charging and balancing protocols with degradation awareness for a string of Li-ion cells

This work introduces and compares low-computational cost MPC-based algorithms based on a reduced-order electrochemical model, the Equivalent Hydraulic Model (EHM), for the fast charge and balance of a string of battery cells accounting for degradation-related phenomena. The balance is carried out through a fully shunting grid. The shunting scenarios are described in two different approaches, namely: binary variables and pulse with modulation (PWM). Due to the complexity of solving nonlinear and non-convex constrained optimal problems, we approximate the balancing grid configurations of the string as subsystems to solve an optimization problem that follows the maximization over current and configuration of the string, while minimizing the charging current of each subsystem. Numerical results show that a PWM-based approach outperforms a mixed-integer approach, showing a charging time three times lower.

A 2.24-pJ/bit 2.5-Gb/s UWB receiver in 28-nm FDSOI CMOS for low-energy chip-to-chip communications

Chip-to-chip communications in high-performance applications such as server racks rely on wireline serial links. In this paper, we present a compact ultra-wideband receiver front-end in 28-nm FDSOI CMOS technology as a wireless interconnect alternative for low-energy and broadcast communications. It is based on binary pulse position modulation without guard interval using two periods of a 10-GHz carrier to reach 2.5-Gb/s datarate over distances >20 cm. The proposed receiver occupies 0.3 mm2 (including decoupling capacitors) and consumes only 5.6 mW which results in an energy of 2.24 pJ/bit.

Maximizing the Data Rate of an Inductively Coupled Chip-to-Chip Link by Resetting the Channel State Variables

A technique is proposed for increasing the data rate transmitted through an inductively coupled chip-to-chip link by resetting the channel state variables. This allows the data rate to be increased well beyond what is implied by the channel bandwidth. In the proposed scheme, the two sides of the link are resonated at the highest possible quality factor, maximizing link gain, and minimizing interference. The transmit signal is a binary matched pulse which maximizes the received signal for a given transmitter voltage limit. High-efficiency switching transmitters can be used for this type of signal. The proposed technique can be applied to communication links in which channel state variables are accessible for reset. For increasing the data rate, it is shown that the proposed state-variable reset technique results in a higher signal-to-noise ratio of the received signal and a higher energy efficiency compared to reducing the quality factor to widen the bandwidth, using equalization, or using multi-level signaling. The technique is demonstrated on a chip-to-chip link with coupled 1.5 mm $\times1.5$ mm planar inductors separated by 0.5 mm in a 0.18 $\mathrm {\mu m}$ CMOS process. 500 Mb/s data rate is achieved over a link which has a band-pass bandwidth of 185 MHz.