Slow Input Research Articles

Granule cells perform frequency-dependent pattern separation in a computational model of the dentate gyrus.

Mnemonic discrimination (MD) may be dependent on oscillatory perforant path input frequencies to the hippocampus in a "U"-shaped fashion, where some studies show that slow and fast input frequencies support MD, while other studies show that intermediate frequencies disrupt MD. We hypothesize that pattern separation (PS) underlies frequency-dependent MD performance. We aim to study, in a computational model of the hippocampal dentate gyrus (DG), the network and cellular mechanisms governing this putative "U"-shaped PS relationship. We implemented a biophysical model of the DG that produces the hypothesized "U"-shaped input frequency-PS relationship, and its associated oscillatory electrophysiological signatures. We subsequently evaluated the network's PS ability using an adapted spatiotemporal task. We undertook systematic lesion studies to identify the network-level mechanisms driving the "U"-shaped input frequency-PS relationship. A minimal circuit of a single granule cell (GC) stimulated with oscillatory inputs was also used to study potential cellular-level mechanisms. Lesioning synapses onto GCs did not impact the "U"-shaped input frequency-PS relationship. Furthermore, GC inhibition limits PS performance for fast frequency inputs, while enhancing PS for slow frequency inputs. GC interspike interval was found to be input frequency dependent in a "U"-shaped fashion, paralleling frequency-dependent PS observed at the network level. Additionally, GCs showed an attenuated firing response for fast frequency inputs. We conclude that independent of network-level inhibition, GCs may intrinsically be capable of producing a "U"-shaped input frequency-PS relationship. GCs may preferentially decorrelate slow and fast inputs via spike timing reorganization and high frequency filtering.

A many-channel FPGA control system.

We describe a many-channel experiment control system based on a field-programmable gate array (FPGA). The system has 16 bit resolution on 10 analog 100 megasamples-per-second (MS/s) input channels, 14 analog 100 MS/s output channels, 16 slow analog input and output channels, dozens of digital inputs and outputs, and a touchscreen display for experiment control and monitoring. The system can support ten servo loops with 155ns latency and MHz bandwidths, in addition to as many as 30 lower bandwidth servos. We demonstrate infinite-impulse-response (IIR) proportional-integral-differential filters with 30ns latency by using only bit-shifts and additions. These IIR filters allow timing margin at 100 MS/s and use fewer FPGA resources than straightforward multiplier-based filters, facilitating many servos on a single FPGA. We present several specific applications: Hänsch-Couillaud laser locks with automatic lock acquisition and a slow dither correction of lock offsets, variable duty cycle temperature servos, and the generation of multiple synchronized arbitrary waveforms.

Multiplexed gradient descent: Fast online training of modern datasets on hardware neural networks without backpropagation

We present multiplexed gradient descent (MGD), a gradient descent framework designed to easily train analog or digital neural networks in hardware. MGD utilizes zero-order optimization techniques for online training of hardware neural networks. We demonstrate its ability to train neural networks on modern machine learning datasets, including CIFAR-10 and Fashion-MNIST, and compare its performance to backpropagation. Assuming realistic timescales and hardware parameters, our results indicate that these optimization techniques can train a network on emerging hardware platforms orders of magnitude faster than the wall-clock time of training via backpropagation on a standard GPU, even in the presence of imperfect weight updates or device-to-device variations in the hardware. We additionally describe how it can be applied to existing hardware as part of chip-in-the-loop training or integrated directly at the hardware level. Crucially, because the MGD framework is model-free it can be applied to nearly any hardware platform with tunable parameters, and its gradient descent process can be optimized to compensate for specific hardware limitations, such as slow parameter-update speeds or limited input bandwidth.

Subthreshold Delay Variation Model Considering Transitional Region for Input Slew

Subthreshold design provides the promising advantage of low power consumption at the cost of performance variation and even circuit failure. An accurate and efficient statistical timing model is crucial for timing analysis and performance optimization guidance. Prior works lack the consideration of the impact of slew time or the transitional region for input slew due to process variation and efficient approaches considering the impact of load capacitance and multiple process variations in complex gates, resulting in accuracy loss. In this work, an accurate end efficient gate delay variation model is analytically derived for various input slews and load capacitances. The transitional region between fast and slow input slew is efficiently partitioned with an adaptive error tolerance method so as to characterize timing variation by linear interpolation based on that for fast and slow input slew. In order to consider the impact of load capacitance, the relation between the sensitivity of step delay and the dominant threshold voltage variation is analytically derived. For complex gates, the multiple process variations for both parallel and stacking structures are equivalently expressed by threshold voltage variation from each transistor. The proposed model has been validated under advanced TSMC (Taiwan Semiconductor Manufacturing Company) 12 nm technology at subthreshold region and achieves excellent agreement with Monte Carlo SPICE (Simulation Program with Integrated Circuit Emphasis) simulation results with the max error less than 6.49% for standard deviation of gate delay and 4.63%/6.40% for max/min delay, demonstrating over 4 times precision improvement compared with competitive analytical models.

SUPERRADIATION OF CLASSICAL OSCILLATORS AT CONSTANT PUMPING

The dependence of the generation efficiency in the superradiance regime of an ensemble of oscillators on the pump energy input rate, as well as on the characteristics of the change in the pump phase, is studied. It is assumed that the pumping phase can vary both in time and in space. The most efficient pumping method remains the mode with slow energy input into the system, in comparison with the characteristic generation time, and the nature of the distribution of the field phase along the system can be either random or with a certain spatial period, but slightly changing with time.

Effect of Direct Slow Pathway Capture Mapping–Guided Ablation on Typical Atrioventricular Nodal Re-Entrant Tachycardia

BackgroundDirect slow pathway capture (DSPC) mapping is a novel electrophysiological technique for detecting antegrade slow pathway input sites. However, the effect of DSPC mapping–guided ablation on atrioventricular nodal re-entrant tachycardia (AVNRT) is unknown. ObjectivesThis study aimed to evaluate the efficacy and safety of DSPC mapping–guided ablation in typical AVNRT patients. MethodsA multicenter retrospective study was conducted in 301 consecutive typical AVNRT patients. The outcomes in patients who underwent DSPC mapping–guided ablation (DSPC group) and those who underwent conventional anatomical ablation (conventional group) were compared. The conventional group was established before introducing DSPC mapping–guided ablation. Positive DSPC sites were defined as sites with a return cycle atrioventricular prolongation of ≥20 ms with high-output (10-20 V) pacing during tachycardia or the last paced beat of the atrial extrastimulation. ResultsAmong 116 patients in the DSPC group, 102 (88%) had positive DSPC sites, and 86 (74%) had a successful ablation at that site. Of the remaining 30 patients, 27 had a successful anatomical ablation. The DSPC group had a significantly lower frequency of radiofrequency applications and shorter total application time than the conventional group (median: 5.5 [IQR: 3-11] times vs 9 [IQR: 5-15] times, and 168 [IQR: 108-266] seconds vs 244 [IQR: 158-391] seconds, respectively; P < 0.01). Moreover, the DSPC group had a numerically lower incidence of permanent pacemaker implantations and AVNRT recurrences than the conventional group (0% vs 1.6%; P = 0.17, and 1.7% vs 3.2%; P = 0.43, respectively). ConclusionsDSPC mapping–guided ablation was associated with a lower operative time, which can reduce the risk of AV conduction injury in typical AVNRT.

Influence of Sewershed Characteristics on Rainfall‐Derived Inflow and Infiltration

ABSTRACTBasement backups and sewer overflows from rainfall‐derived inflow and infiltration (RDII) are a significant threat to human and environmental health; however, reducing inflow and infiltration is a challenge for municipalities due to the difficulty and resources required to accurately identify source areas. This case study seeks to address this challenge by evaluating the influence that sewershed characteristics have on inflow and infiltration into sanitary sewer systems. To do so, we used 4.5 years of monitoring data from 19 sanitary sewer locations in Milwaukee, Wisconsin to explore the relationships between RDII defined using the RTK unit hydrograph method and sewershed physical, land cover, and pipe characteristics. Results demonstrate that inflow, or fast direct flows into the system, is positively correlated to pipe length per acre, number of parcels, and medium intensity land use. Infiltration, or slow inputs from groundwater sources, is negatively correlated with imperviousness, pipe length per acre, low intensity, and medium intensity land use. Multivariable linear regression using these parameters explained between 55% and 72% of the variance in normalized inflow and infiltration. These findings demonstrate a way in which collection system managers may be able to narrow the search areas for RDII sources within their sanitary sewer systems by evaluating sewershed characteristics.

PENGARUH KUALITAS PELAYANAN KARTU KREDIT TERHADAP KEPUASAN KONSUMEN PADA BANK KB BUKOPIN REGIONAL BANDUNG

This research purposed to know how the effect of the quality of credit card service on consumer satisfaction in Bank KB Bukopin Regional Bandung. The research method was used in this research was a verifiable descriptive method by collecting data from field studies, questionnaires and literate studies. The population in this research is a credit card consumer with 40 samples by using sample random sampling method. Primary data in this research are derived from a questionnaire that measures a Likert scale and was statistically treated with an SPSS version 26.0 program, while the data analysis techniques were used simple linear regression and intervariabel correlation techniques. From the research that had been done, there was concluded that the quality of the service has a solid relation with consumer satisfaction. This is known from a coefficient value of credit card services to consumer satisfaction at 0.863 at high relations rates interval. The result of the t hypothesis test stated that there was an effect between the quality of credit card service to consumer satisfaction in Bank KB Bukopin Regional Bandung because it had a higher value t than t table (10.54 &gt; 1.68595). The problem encountered is the high level of consumer complaints about the slow input of data on the system at the Bukopin Bank for every credit card payment

Weather optimal area-keeping control for underactuated autonomous surface vehicle with input time-delay

The problem of the underactuated Autonomous Surface Vehicle (ASV) area-keeping control under unknown slow time-varying external environment disturbances and input time-delay, an integral time-delay sliding mode control algorithm based on weather optimal intermittent strategy is proposed in this article. Firstly, integral time-delay sliding mode control law is constructed, with controller parameters chosen according to the upper bound of time-delay. In the control law, a geometric updating rule is designed for the virtual suspension point, which enables ASV at a particular small area with a weather optimal heading. And, weather optimal intermittent strategy is developed to extend the area-keeping control method, while reducing ASV energy consumption. Besides, the closed-loop system is globally asymptotically stable through Lyapunov-Krasovskii analysis. Finally, the performance of the proposed algorithm is illustrated through the simulation examples.

A Reference-Sampling Based Calibration-Free Fractional-N PLL with a PI-Linked Sampling Clock Generator.

Sampling-based PLLs have become a new research trend due to the possibility of removing the frequency divider (FDIV) from the feedback path, where the FDIV increases the contribution of in-band noise by the factor of dividing ratio square (N2). Between two possible sampling methods, sub-sampling and reference-sampling, the latter provides a relatively wide locking range, as the slower input reference signal is sampled with the faster VCO output signal. However, removal of FDIV makes the PLL not feasible to implement fractional-N operation based on varying divider ratios through random sequence generators, such as a Delta-Sigma-Modulator (DSM). To address the above design challenges, we propose a reference-sampling-based calibration-free fractional-N PLL (RSFPLL) with a phase-interpolator-linked sampling clock generator (PSCG). The proposed RSFPLL achieves fractional-N operations through phase-interpolator (PI)-based multi-phase generation instead of a typical frequency divider or digital-to-time converter (DTC). In addition, to alleviate the power burden arising from VCO-rated sampling, a flexible mask window generation method has been used that only passes a few sampling clocks near the point of interest. The prototype PLL system is designed with a 65 nm CMOS process with a chip size of 0.42 mm2. It achieves 322 fs rms jitter, −240.7 dB figure-of-merit (FoM), and −44.06 dBc fractional spurs with 8.17 mW power consumption.

Pharmacokinetics of a high-concentration formulation of buprenorphine (Simbadol) in male dogs

ObjectiveTo describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine. Study designProspective, randomized, crossover study. AnimalsA total of six healthy male intact Beagle dogs, aged 9–13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation). MethodsDogs were randomized to be administered buprenorphine (0.12 mg kg–1; Simbadol, 1.8 mg mL–1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography–tandem mass spectrometry. ResultsA three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg–1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute–1 kg–1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80–239)%. Calculated terminal half-life was 963 minutes. Conclusions and clinical relevanceThe high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues.

Controlling the release rate of topotecan from PLGA spheres and increasing its cytotoxicity towards glioblastoma cells by co-loading with calcium chloride

It has been suggested that local administration of topotecan (TT) could increase its efficacy in the treatment of glioblastoma. In this context, a PLGA implant model in the form of spheres with a porous core and stiff surface, loaded with TT and CaCl2 was developed. An array of formulations differing from each other by the type of PLGA used, the integrity of the surface, the concentrations of TT and CaCl2 added during the preparation, and the volume of water in the PLGA mix, was prepared, screened and explored by computerized multifactorial analysis. This analysis enabled the simultaneous identification of the most influential experimental factors on the experimental responses, which were pre-determined as the efficiency of TT loading and the TT % cumulative release at 14 days. The multifactorial analysis also revealed how the interactions among the experimental factors affect the performance of the various formulations. Thus, TT concentration and its factorial interaction with the concentration of CaCl2 added during the spheres’ preparation were identified as most prominent on the loading efficiency, while the surface integrity (intact or punctured) and CaCl2 amount in the spheres were identified as most prominent on the TT % cumulative release from the spheres. TT was found to be cytotoxic towards glioblastoma U87 MG cells, an activity which was enhanced, synergistically, in the presence of CaCl2 (the relative viability was reduced from 36 to 28% with combination indices of 1.0, 0.37, 0.13 and 0.06 for EC50, EC75, EC90 and EC95, respectively). Interestingly, dividing the TT dose into 3 equal portions, replenished daily to the incubation medium, increased TT cytotoxicity. The relative viability was then reduced from 35 to 7% and in the presence of CaCl2 – from 28 to 1.9%, suggesting that a local, slow input of TT could be effective in the treatment of glioblastoma by an adjacent TT implant. The increased effect of CaCl2 on cytotoxicity was also observed when it was co-loaded into the TT spheres. In that case, the cells’ viability was reduced from 72 to 27%. It is suggested that the PLGA spheres could be used for tunable local delivery of TT in post-resection adjuvant therapy of glioblastoma.

Differential contributions of synaptic and intrinsic inhibitory currents to speech segmentation via flexible phase-locking in neural oscillators.

Current hypotheses suggest that speech segmentation-the initial division and grouping of the speech stream into candidate phrases, syllables, and phonemes for further linguistic processing-is executed by a hierarchy of oscillators in auditory cortex. Theta (∼3-12 Hz) rhythms play a key role by phase-locking to recurring acoustic features marking syllable boundaries. Reliable synchronization to quasi-rhythmic inputs, whose variable frequency can dip below cortical theta frequencies (down to ∼1 Hz), requires "flexible" theta oscillators whose underlying neuronal mechanisms remain unknown. Using biophysical computational models, we found that the flexibility of phase-locking in neural oscillators depended on the types of hyperpolarizing currents that paced them. Simulated cortical theta oscillators flexibly phase-locked to slow inputs when these inputs caused both (i) spiking and (ii) the subsequent buildup of outward current sufficient to delay further spiking until the next input. The greatest flexibility in phase-locking arose from a synergistic interaction between intrinsic currents that was not replicated by synaptic currents at similar timescales. Flexibility in phase-locking enabled improved entrainment to speech input, optimal at mid-vocalic channels, which in turn supported syllabic-timescale segmentation through identification of vocalic nuclei. Our results suggest that synaptic and intrinsic inhibition contribute to frequency-restricted and -flexible phase-locking in neural oscillators, respectively. Their differential deployment may enable neural oscillators to play diverse roles, from reliable internal clocking to adaptive segmentation of quasi-regular sensory inputs like speech.

Two-Timescale Missile Autopilot Design Based on Suboptimal Control

Aiming at the missile longitudinal motion model with obvious aerodynamic nonlinearity, this paper proposes a two-timescale design method of missile autopilot based on suboptimal control. By dividing the system states into fast and slow states based on different timescales, the corresponding fast and slow control inputs are designed. This paper introduces suboptimal control and robust control to enable the system to have good dynamic response characteristics, and the system’s ability to suppress various uncertainties is guaranteed. By applying the Lyapunov method, the stability conditions of the system are given. Finally, the simulation results show that the system has good dynamic characteristics and robustness.

Pharmacokinetics of a high concentration formulation of buprenorphine (Simbadol) in male dogs

Abstract Objective To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine. Study design Prospective, randomized, crossover study. Animals A total of six healthy male intact Beagle dogs, 9–13 months of age and weighing 10.3 ± 1.4 kg (mean ± standard deviation). Methods Dogs were randomized to be administered buprenorphine (0.12 mg kg−1; Simbadol, 1.8 mg mL−1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography–tandem mass spectrometry. Results A 3-compartment model with zero or biphasic rapid and slow first order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg−1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute−1 kg−1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minutes delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80–239) %. Calculated terminal half-life was 963 minutes. Conclusions and clinical relevance The high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues.

Full-State Feedback Control Design for Shape Formation using Linear Quadratic Regulator

This study investigated the capability of a group of agents to form a desired shape formation by designing the feedback control using a linear quadratic regulator. In real application, the state condition of agents may change due to some particular problems such as a slow input response. In order to compensate for the problem that affects agent-to-agent coordination, a robust regulator was implemented into the formation algorithm. In this study, a linear quadratic regulator as the full-state feedback of robust regulator method for shape formation was considered. The result showed that a group of agents can form the desired shape (square) formation with a modification of the trajectory shape of each agent. The results were validated through numerical experiments.

Application of microcosm experiments for quantifying lateral flow and evapotranspiration on recovering bog ecotypes.

The importance of characterizing the ecohydrological interactions in natural, damaged/drained, and restored bogs is underscored by the importance of peatlands to global climate change and the growing need for peatland restoration. An understudied aspect of peatland ecohydrology is how shallow lateral flow impacts local hydrological conditions and water balance, which are critical for peatland restoration success. A novel method is presented using microcosms installed in the field to understand the dynamics of shallow lateral flow. Analysis of the difference in water table fluctuation inside and outside the microcosm experimental areas allowed the water balance to be constrained and the calculation of lateral flow and evapotranspiration. As an initial demonstration of this method, a series of four microcosm experiments were set up in locations with differing ecological quality and land management histories, on a raised bog complex in the midlands of Ireland. The timing and magnitude of the lateral flow differed considerably between locations with differing ecological conditions, indicating that shallow lateral flow is an important determining factor in the ecohydrological trajectory of a recovering bog system. For locations where Sphagnum spp. moss layer was present, a slow continuous net lateral input of water from the upstream catchment area supported the water table during drought periods, which was not observed in locations lacking Sphagnum. Consistent with other studies, evapotranspiration was greater in locations with a Spaghnum moss layer than in locations with a surface of peat soil.

Dynamic Bayesian Adjustment of Dwell Time for Faster Eye Typing.

Eye typing is a hands-free method of human computer interaction, which is especially useful for people with upper limb disabilities. Users select a desired key by gazing at it in an image of a keyboard for a fixed dwell time. There is a tradeoff in selecting the dwell time; shorter dwell times lead to errors due to unintentional selections, while longer dwell times lead to a slow input speed. We propose to speed up eye typing while maintaining low error by dynamically adjusting the dwell time for each letter based on the past input history. More likely letters are assigned shorter dwell times. Our method is based on a probabilistic generative model of gaze, which enables us to assign dwell times using a principled model that requires only a few free parameters. We evaluate our model on both able-bodied subjects and subjects with a spinal cord injury (SCI). Compared to the standard dwell time method, we find consistent increases in typing speed in both cases. e.g., 41.8% faster typing for able-bodied subjects on a transcription task and 49.5% faster typing for SCI subjects in a chatbot task. We observed more inter-subject variability for SCI subjects.

Atrioventricular junctional ablation: The good, the bad, the better.

BackgroundThe management of patients with atrial fibrillation and an abnormally fast ventricular response has been through the use of pharmacologic agents. In those cases where rate control cannot be achieved pharmacologically, a standard approach has been atrioventricular (AV) junctional ablation and ventricular pacemaker implantation to achieve a stable ventricular rate. Long-term ventricular pacing has been shown to result in diminished ventricular function that can lead to heart failure.ObjectiveTo describe an experimental and clinical study demonstrating a modified form of AV junction ablation.MethodsAblation of the slow and fast AV nodal input does not produce AV block. Ablation of the connection between the two induces AV block, leaving the AV node and His bundle intact.ResultsSubsequently the escape heart rate is close to normal and responds well to exercise.ConclusionIn a clinical study with a 42 month follow-up, the modified procedure resulted in significantly reduced pacemaker dependence and mortality compared to the standard AV ablation procedure.

Inflatable soft jumper inspired by shell snapping.

Fluidic soft actuators are enlarging the robotics toolbox by providing flexible elements that can display highly complex deformations. Although these actuators are adaptable and inherently safe, their actuation speed is typically slow because the influx of fluid is limited by viscous forces. To overcome this limitation and realize soft actuators capable of rapid movements, we focused on spherical caps that exhibit isochoric snapping when pressurized under volume-controlled conditions. First, we noted that this snap-through instability leads to both a sudden release of energy and a fast cap displacement. Inspired by these findings, we investigated the response of actuators that comprise such spherical caps as building blocks and observed the same isochoric snapping mechanism upon inflation. Last, we demonstrated that this instability can be exploited to make these actuators jump even when inflated at a slow rate. Our study provides the foundation for the design of an emerging class of fluidic soft devices that can convert a slow input signal into a fast output deformation.