Variable Delay Research Articles

Rhythmic Entrainment Echoes in Auditory Perception.

Rhythmic entrainment echoes-rhythmic brain responses that outlast rhythmic stimulation-can demonstrate endogenous neural oscillations entrained by the stimulus rhythm. Here, we tested for such echoes in auditory perception. Participants detected a pure tone target, presented at a variable delay after another pure tone that was rhythmically modulated in amplitude. In four experiments involving 154 human (female and male) participants, we tested (1) which stimulus rate produces the strongest entrainment echo and, inspired by the tonotopical organization of the auditory system and findings in nonhuman primates, (2) whether these are organized according to sound frequency. We found the strongest entrainment echoes after 6 and 8 Hz stimulation, respectively. The best moments for target detection (in phase or antiphase with the preceding rhythm) depended on whether sound frequencies of entraining and target stimuli matched, which is in line with a tonotopical organization. However, for the same experimental condition, best moments were not always consistent across experiments. We provide a speculative explanation for these differences that relies on the notion that neural entrainment and repetition-related adaptation might exercise competing opposite influences on perception. Together, we find rhythmic echoes in auditory perception that seem more complex than those predicted from initial theories of neural entrainment.SIGNIFICANCE STATEMENT Rhythmic entrainment echoes are rhythmic brain responses that are produced by a rhythmic stimulus and persist after its offset. These echoes play an important role for the identification of endogenous brain oscillations, entrained by rhythmic stimulation, and give us insights into whether and how participants predict the timing of events. In four independent experiments involving >150 participants, we examined entrainment echoes in auditory perception. We found that entrainment echoes have a preferred rate (between 6 and 8 Hz) and seem to follow the tonotopic organization of the auditory system. Although speculative, we also found evidence that several, potentially competing processes might interact to produce such echoes, a notion that might need to be considered for future experimental design.

A modelling analysis of a new multi-stage pathway for classifying achievement of public health milestones for leprosy.

Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination. We use a simple probabilistic model to simulate the stochastic dynamics of detected cases as transmission declines, and evaluate progress through the new public health milestones. In simulations where transmission is halted, 5 years of zero incidence in autochthonous children, combined with 3 years of zero incidence in allages is a flawed indicator that transmission has halted (54% correctly classified). A further 10 years of only occasional sporadic cases is associated with a high probability of having interrupted transmission (99%). If, however, transmission continues at extremely low levels, it is possible that cases could be misidentified as historic cases from the tail of the incubation period distribution, although misleadingly achieving all three milestones is unlikely (less than 1% probability across a 15-year period of ongoing low-level transmission). These results demonstrate the feasibility and challenges of a phased progression of milestones towards interruption of transmission, allowing assessment of programme status. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

The psychophysics of bouncing: Perceptual constraints, physical constraints, animacy, and phenomenal causality.

In the present study we broadly explored the perception of physical and animated motion in bouncing-like scenarios through four experiments. In the first experiment, participants were asked to categorize bouncing-like displays as physical bounce, animated motion, or other. Several parameters of the animations were manipulated, that is, the simulated coefficient of restitution, the value of simulated gravitational acceleration, the motion pattern (uniform acceleration/deceleration or constant speed) and the number of bouncing cycles. In the second experiment, a variable delay at the moment of the collision between the bouncing object and the bouncing surface was introduced. Main results show that, although observers appear to have realistic representations of physical constraints like energy conservation and gravitational acceleration/deceleration, the amount of visual information available in the scene has a strong modulation effect on the extent to which they rely on these representations. A coefficient of restitution >1 was a crucial cue to animacy in displays showing three bouncing cycles, but not in displays showing one bouncing cycle. Additionally, bouncing impressions appear to be driven by perceptual constraints that are unrelated to the physical realism of the scene, like preference for simulated gravitational attraction smaller than g and perceived temporal contiguity between the different phases of bouncing. In the third experiment, the visible opaque bouncing surface was removed from the scene, and the results showed that this did not have any substantial effect on the resulting impressions of physical bounce or animated motion, suggesting that the visual system can fill-in the scene with the missing element. The fourth experiment explored visual impressions of causality in bouncing scenarios. At odds with claims of current causal perception theories, results indicate that a passive object can be perceived as the direct cause of the motion behavior of an active object.

5.7 ps Resolution Time-to-Digital Converter Implementation Using Routing Path Delays

A tapped delay line (TDL)-based time-to-digital converter (TDC) implemented on an FPGA (Field Programmable Gate Array) is sensitive to nonlinearities because of significant variations in the delay of the delay elements. Most of the nonlinearity of FPGA-based TDCs comes from the routing of the design. It is promising to realize TDCs using internal routing resources available in FPGAs, as these devices contain a lot of routing resources and are resistant to voltage and temperature changes. This work implements and tests a TDC based on a series of counters driven by a variable delay line that exploits the internal routing resources available in the FPGA as delay elements. A manual placement and routing technique that results in greater resolution and linearity is proposed. The time-interleaving concept is used to improve the resolution of the TDC. A measurement matrix with 512 and 1024 parallel counters is implemented on a Zynq Evaluation and Development (ZED) board. The result of the 1024-unit TDC showed that a dynamic range of 93.6 ns can be measured using a 4-bit coarse gray code counter running at a reference frequency of 171 MHz, and a resolution of 5.7 ps is achieved. The implemented TDC is low-cost, has a fast time to market, and it benefits from the abundant routing resources in the FPGA.

New results for the upper bounds of the distance between adjacent zeros of first-order differential equations with several variable delays

The distance between consecutive zeros of a first-order differential equation with several variable delays is studied. Here, we show that the distribution of zeros of differential equations with variable delays is not an easy extension of the case of constant delays. We obtain new upper bounds for the distance between zeros of all solutions of a differential equation with several delays, which extend and improve some existing results. Two illustrative examples are given to show the advantages of the proposed results over the known ones.

AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia

Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the β-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity. All three AXIN1-truncating variants resulted in reduced protein levels and impaired AXIN1 polymerization mediated by its C-terminal DIX domain but partially retained Wnt-inhibitory function upon overexpression. Addition of a tankyrase inhibitor attenuated Wnt overactivity in the AXIN1-mutant model systems. Our data suggest that AXIN1 coordinates the action of osteoblasts and osteoclasts and that tankyrase inhibitors can attenuate the effects of AXIN1 hypomorphic variants.

New results on the existence and uniqueness of positive almost periodic solution for the generalized Mackey–Glass hematopoietic model

This paper is concerned with the solution of the generalized hematopoietic model with multiple variable delays and multiple exponents. By using the fixed point theorem for mixed monotone operators, we prove that the generalized Mackey–Glass hematopoietic model has a unique positive almost periodic solution, and derive various new existence and uniqueness results under weaker conditions. Then, an iterative sequence is established and shown to converge to the unique solution under various conditions. Finally, four examples are given to illustrate the application of our theoretical results.

Consensus for Hegselmann–Krause type models with time variable time delays

In this paper, we analyze a Hegselmann–Krause opinion formation model with time variable time delay and prove that if the influence function is always positive, then there is exponential convergence to consensus without requiring any smallness assumptions on the time delay function. The analysis is then extended to a model with distributed time delay.

Optimized Design of a Variable Fractional Delay Filter With Delay Error Constraints

A novel algorithm for designing variable fractional delay (VFD) filter coefficients is proposed to improve time delay accuracy. The principle of this method is to model the coefficient design as an optimization problem with fractional delay error constraints (FDECs) and use a linear approach to derive a new FDEC expression for solving the problem. The solution of the FDEC expression can be efficiently obtained through linear programming (LP). Compared with existing algorithms, the design examples show the proposed method achieves a 100-fold improvement in delay accuracy while maintaining the frequency response (FR) error at an acceptable level, and yields a 5 dB reduction in FR error with the same level of delay accuracy.

Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ10 deficiency: Hypomorphic variants and two distinct disease entities.

Primary coenzyme Q10 (CoQ10) deficiency is a group of inborn errors of metabolism caused by defects in CoQ10 biosynthesis. Biallelic pathogenic variants in COQ7, encoding mitochondrial 5-demethoxyubiquinone hydroxylase, have been reported in nine patients from seven families. We identified five new patients with COQ7-related primary CoQ10 deficiency, performed clinical assessment of the patients, and studied the functional effects of current and previously reported COQ7 variants and potential treatment options. The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involvement and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay. Baker's yeast orthologue of COQ7, CAT5, is required for growth on oxidative carbon sources and cat5Δ strain demonstrates oxidative growth defect. Expression of wild-type CAT5 could completely rescue the defect; however, yeast CAT5 harboring equivalent human pathogenic variants could not. Interestingly, cat5Δ yeast harboring p.Arg57Gln (equivalent to human p.Arg54Gln), p.Arg112Trp (equivalent to p.Arg107Trp), p.Ile69Asn (equivalent to p.Ile66Asn) and combination of p.Lys108Met and p.Leu116Pro (equivalent to the complex allele p.[Thr103Met;Leu111Pro]) partially rescued the growth defects, indicating these variants are hypomorphic alleles. Supplementation with 2,4 dihydroxybenzoic acid (2,4-diHB) rescued the growth defect of both the leaky and severe mutants. Overexpression of COQ8 and 2,4-diHB supplementation synergistically restored oxidative growth and respiratory defect. Overall, we define two distinct disease presentations of COQ7-related disorder with emerging genotype-phenotype correlation and validate the use of the yeast model for functional studies of COQ7 variants.

Evolution of Feeding and Developmental Outcomes in Infants With Moderate Hypoxic-Ischemic Encephalopathy: A Pilot Study.

The purpose of the study was to describe the evolution of outcomes among full-term infants with moderate hypoxic-ischemic encephalopathy (HIE); from their early swallowing and feeding abilities during hospitalization, to their later developmental outcomes at 6 and 12 months. Four participants with moderate HIE were recruited. Early feeding and swallowing were assessed using the Neonatal Feeding Assessment Scale and video fluoroscopic swallow studies. Developmental assessments were conducted at 6 and 12 months using the Rossetti Infant-Toddler Language Scale and Vineland-3 Scale. All participants displayed atypical outcomes throughout the study, including oropharyngeal dysphagia initially during hospitalization. All participants were discharged on oral feeds but some breastfeeding difficulties persisted. Variable but pervasive developmental delays were found among all participants at 6 and 12 months. This study emphasizes the need for consistent early intervention from the neonatal period onward, for all infants with moderate HIE. Future studies should use larger cohorts, longer follow-up, and correlational designs.

Wavelets approach for the solution of nonlinear variable delay differential equations

Abstract In this study, the Laguerre wavelet-oriented numerical scheme for nonlinear first and second-order delay differential equations (DDEs) is offered. The proposed technique is dependent on the truncated series of the Laguerre wavelets approximation of an unknown function. Here, we transform the different ordered DDEs into a system of non-linear algebraic equations with the help of limit points of a sequence of collocation points. Four nonlinear illustrations are involved to prove the efficiency of the planned technique. the Obtained results are equated with the current results, indicating the proposed technique’s accuracy and efficiency.

Exact Solutions of Reaction–Diffusion PDEs with Anisotropic Time Delay

This study is devoted to reaction–diffusion equations with spatially anisotropic time delay. Reaction–diffusion PDEs with either constant or variable transfer coefficients are considered. Nonlinear equations of a fairly general form containing one, two, or more arbitrary functions and free parameters are analyzed. For the first time, reductions and exact solutions for such complex delay PDEs are constructed. Additive, multiplicative, generalized, and functional separable solutions and some other exact solutions are presented. In addition to reaction–diffusion equations, wave-type PDEs with spatially anisotropic time delay are considered. Overall, more than twenty new exact solutions to reaction–diffusion and wave-type equations with anisotropic time delay are found. The described nonlinear delay PDEs and their solutions can be used to formulate test problems applicable to the verification of approximate analytical and numerical methods for solving complex PDEs with variable delay.

Age differences in the neural correlates of recollection: transient versus sustained fMRI effects

Prior functional magnetic resonance imaging findings in young adults indicate that recollection-sensitive neural regions dissociate according to the time courses of their respective recollection effects. Here, we examined whether such dissociations are also evident in older adults. Young and older participants encoded a series of word-image pairs, judging which of the denoted objects was the smaller. At the test, participants judged whether each of a series of test words was old or new. If a word was old, the requirement was to recall the associated image and maintain it over a variable delay period. Older adults demonstrated significantly lower associative memory performance than young adults. Transient recollection effects were identified in the left hippocampus, medial prefrontal cortex, and posterior cingulate, while sustained effects were widespread across left lateral cortex and were also evident in the bilateral striatum. Except for those in the left insula, all effects were age-invariant. These findings suggest that both transient and sustained recollection effects are largely stable across much of the healthy adult life span.

Spiking neural P systems with myelin and dendritic spines

Inspired by the dendritic and axonal morphology, some authors modeled the transmission speed of action potentials through of fixed dendritic and axonal delays, respectively. However, in practice, the exploration of dendrites and axons with variable delays potentially allows the improvement of advanced engineering applications. Taking inspiration from the structure of the dendritic spines and the process of myelination of axons, we introduce a new variant of the spiking neural P systems with variable axonal and dendritic delays named as a spiking neural P system with myelin and dendritic spines computation (MDSCSN P system). The inclusion of these experimentally proven biological features of axon and dendrites into standard spiking neural P systems allows to control the timing of dendritic/axonal transmissions. As a consequence, the soma processing of neurons is significantly reduced since it receives stable firing patterns. In contrast, standard spiking neural P systems and their recent variants use a large number of neurons/synapses to do the same. To demonstrate this, we generate a small universal SN P system by employing only neurons with standard rules to perform any Turing computable function and to figure out the Subset Sum problem in the uniform way.

Design and simplified stability analysis of wide-area damping control with variable feedback delay

Poorly damped low-frequency inter-area oscillations are a major concern in large power systems. Wide-area damping controllers which modulate power flow using power electronic systems like HVDC links and FACTS can be used to improve the damping of the critical modes in a targeted manner. These controllers use wide-area measurements, which are communicated from several remote locations. The communication time delay is generally variable in nature, and the data from different locations arrive at the controller with different delays. The overall delay in synthesizing the controller input signal affects the closed-loop damping performance. This paper proposes a delay-handling strategy and derives a discrete-time model which is used to characterize its performance. The relative insensitivity of the mode shape of swing modes to the damping controller is used to facilitate a simplified analysis. A strategy for the adaptation of controller gain when the delays are excessive and persistent is also presented. A case study is presented to illustrate the delay-handling and gain adaptation strategies.

Cascaded Reflection-Type Group Delay Controller With a Wideband Flat Group Delay

This letter presents a wideband group delay controller (GDC) based on cascaded reflection-type phase shifters (RTPSs). Frequency tunable resonators are used as the reflective loads of each phase shifter so that the phase shifter has a variable group delay resulting in a reflection-type GDC (RTGDC). Two RTGDCs with different types of reflective loads are cascaded to compensate for their group delay variation over frequency. The first and the second stage of the cascaded RTGDC are respectively in charge of the delay in low and high-frequency bands and the cascaded delay is flat over a wide bandwidth. The proposed cascaded RTGDC operates at 3.7 GHz over 200-MHz bandwidth. The measured group delay varies from 0.67 to 2.18 ns, which is a 1.51-ns group delay variation under 9.1% normalized group delay variation over the bandwidth. The return loss is over 18 dB and the insertion loss is 2.1 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\pm$</tex-math> </inline-formula> 1.3 dB at 3.7 GHz.

A Low-Cost Measurement Methodology for LiDAR Receiver Integrated Circuits

This paper presents a test methodology to facilitate the measuring processes of LiDAR receiver ICs by avoiding the inherent walk error issue. In a typical LiDAR system, a costly laser diode driver emits narrow light pulses with fast rising edges, and the reflected pulses from targets enter an optical detector followed by an analog front-end (AFE) circuit. Then, the received signals pass through the cascaded amplifiers down to the time-to-digital converter (TDC) that can estimate the detection range. However, this relatively long signal journey leads to the significant decline of rising-edge slopes and the output pulse spreading, thus producing inherent walk errors in LiDAR receiver ICs. Compensation methods requiring complex algorithms and extra chip area have frequently been exploited to lessen the walk errors. In this paper, however, a simpler and lower-cost methodology is proposed to test LiDAR receiver ICs by employing a high-speed buffer and variable delay cells right before the TDC. With these circuits, both START and STOP pulses show very similar pulse shapes, thus effectively avoiding the walk error issue. Additionally, the time interval between two pulses is easily determined by varying the number of the delay cells. Test chips of the proposed receiver IC implemented in a 180-nm CMOS process successfully demonstrate easier and more accurate measurement results.

Exponential attractor for Kirchhoff model with time delay and thermal effect

The Kirchhoff model is derived from the vibration problem of stretchable strings. In this paper, we focus on the long-time dynamics of the Kirchhoff model with time delay and thermal effect. We first proved the existence and uniqueness of the solution through the Faedo–Galerkin method and prior estimates. After that, it is further proved that the dynamical system has a bounded absorption set, and it is also verified that the system is quasi-stable on the bounded absorbing set. Finally, the existence of exponential attractor in dynamical system is proved. This innovatively considers the long-time dynamical behavior of Kirchhoff model under the simultaneous action of variable coefficient, thermal effect and time delay comprehensively. It also promotes the relevant conclusions of the Kirchhoff model. The findings of this paper provide a theoretical basis for subsequent application and research.

199-OR: Optogenetic Control of Pancreatic Delta Cells Reveals Their Central Role in Hormone Release from Pancreatic Islets

Diabetes mellitus is a metabolic disorder resulting from insufficient insulin release and associated with dysregulation of glucagon secretion. Somatostatin secreted from pancreatic δ-cells is a strong paracrine factor for both insulin and glucagon secretion in islets. Here, we developed an optogenetic approach, through specific expressing light-sensitive channels/pumps in δ-cells, to investigate the paracrine control of hormone release from islets. We generated mouse models that express either a light-sensitive cation channel, channelrhodopsin-2 (ChR2), or a chloride pump, halorhodopsin (HR), specifically in the pancreatic δ-cells (SST-ChR2 and SST-HR mouse). Their specific expression was confirmed by immunostaining. Optoactivation of ChR2 at 1mM glucose rapidly depolarized δ-cells by 37mV (n=5) and stimulated electrical activity and somatostatin release. At high glucose or tolbutamide, light activation of HR repolarized δ-cells by 15 mV (n=3), suppressing action potentials. Optoactivation of SST-ChR2 δ-cells suppressed, after a variable delay depending on the distance from δ-cells, action potential firing in neighbouring α-cells, inhibited exocytosis by 30% (n=5) and glucagon secretion by 55% at 1mM glucose (n=7). In a subset (35%) α-cells with no spontaneous action potentials, opto-inhibition of SST-HR δ-cells caused a 9mV depolarization (n=7) and induced action potential firing, which may account for the stimulation of glucagon secretion. Neither optoactivation, nor opto-inhibition of δ-cells affected insulin secretion at hypo- and hyperglycaemia. However, at normoglycaemia (6 mM glucose), optoactivation of δ-cells depolarized neighbouring β-cells (via gap-junctions) and evoked action potential firing, leading to a paradoxical 160% stimulation of insulin secretion (n=9). We conclude that δ-cells play a central role in the regulation of both insulin and glucagon release but that the effects are more complex than appreciated to date. Disclosure H.Dou: None. C.A.Miranda: None. J.Tolö: None. Q.Zhang: None. P.Rorsman: None. Funding Swedish Research Council