Mechanism Of Pulse Generation Research Articles

FRI275 Glutamate Receptor Agonists Stimulate Kisspeptin Neurons In The Arcuate Nucleus Of The Hypothalamus

Abstract Disclosure: R. Bearss: None. R. Piet: None. KNDy neurons co-express kisspeptin, neurokinin B (NKB), dynorphin A (Dyn A), and glutamate. These neurons, located in the arcuate nucleus of the hypothalamus, drive pulsatile gonadotropin releasing hormone (GnRH) secretion. This eventually promotes pulsatile gonadotropin hormone release from the anterior pituitary, important for fertility in both sexes. The current hypothesized mechanism for pulse generation involves KNDy neuron interconnectivity and reciprocal regulation through the combined actions of NKB, DynA and glutamate to coordinate KNDy neuron activity. There is evidence that KNDy neurons express NKB, Dyn A and glutamate receptors and that NKB stimulates KNDy neuron electrical activity while Dyn A suppresses it. There is also evidence that ionotropic glutamate receptor antagonists can inhibit KNDy neuron coordinated activity and pulsatile gonadotropin hormone release, indicating that glutamatergic neurotransmission plays a significant role in activity coordination. The purpose of the following experiments was to investigate the response of KNDy neurons to varied glutamate receptor activation. We used calcium imaging to monitor the activity of KNDy neurons in brain slices. We crossed Kiss1-Cre mice—expressing Cre recombinase (Cre) in kisspeptin neurons—with Cre-dependent GCaMP6f mice to generate Kiss1-Cre x GCaMP6f mice that express GCaMP6f in kisspeptin neurons. GCaMP6f fluorescence increases when binding to intracellular calcium and can, thus, be used as an inferential marker of electrical activity. Coronal brain slices (200 µm thickness) obtained from male Kiss1-cre x GCaMP6f mice and containing the arcuate nucleus were placed in a recording chamber under an epifluorescence microscope. KNDy neurons were exposed for 2 minutes to a bath application of either the ionotropic glutamate receptor agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 10µM), the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA, 50µM), or the group 1 metabotropic glutamate receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG, 50µM). AMPA, NMDA, and DHPG increased KNDy neuron fluorescence by 7.8±0.5% (n=113 in 7 slices from 6 mice), 7.5±0.5% (n=154 in 6 slices from 5 mice), and 6.1±0.7% (n=159 in 7 slices from 5 mice) respectively. All cells that were excited by NMDA or DHPG were also excited by AMPA. These experiments provide evidence that activation of ionotropic AMPA and NMDA receptors as well as group 1 mGluRs stimulate KNDy neuron activity. Further investigation into the precise role of individual glutamate receptor subtypes on KNDy neuron coordinated activity is needed. Presentation: Friday, June 16, 2023

KNDy neurons as the GnRH pulse generator: Recent studies in ruminants

This review considers three aspects of recent work on the role of KNDy neurons in GnRH pulse generation in ruminants. First, work on basic mechanisms of pulse generation includes several tests of this hypothesis, all of which support it, and evidence that Kiss1r-containing neurons form a positive feedback circuit with the KNDy neural network that strengthen the activity of this network. The second section on pathways mediating external inputs focuses on the influence of nutrition and photoperiod, and describes the evidence supporting roles for proopiomelanocortin (POMC) and agouti-related peptide (AgRP) afferents to KNDy cells in each of these. Finally, we review studies exploring the potential applications of manipulating signaling by kisspeptin, and the other KNDy peptides, to control reproductive function in domestic animals and conclude that, although these approaches show some promise, they do not have major advantages over current practices at this time.

Development of a Simulator Capable of Generating Age-Specific Pulse Pressure Waveforms for Medical Palpation Training

With the emergence of the metaverse and other human–computer interaction technologies, promising applications such as medical palpation training are growing for training and education purposes. Thus, the overarching goal of this study is to develop a portable and simple pulse pressure simulator that can reproduce age-specific pulse pressure waveforms for medical palpation training. For training applications, the simulator is required to produce accurate radial pulse waveforms consistently and repeatedly. To this end, exploiting the cam-based pneumatic pulse generation mechanism, this study intends to develop a cylindrical (or 3D) cam whose continually varying surface contains a wide range of age-related pulse pressure profiles. To evaluate the performance of the simulator, the reproduced pulse waveforms were compared with approximate radial pulse pressure waveforms based on in vivo data in terms of the augmentation index (AI) and L2 error. The results show that the errors were less than 10% for all ages, indicating that the proposed pulse simulator can reproduce the age-specific pulse waveforms equivalent to human radial pulse waveforms. The findings in this study suggest that the pulse simulator would be an excellent system for RAPP palpation training as it can reproduce a desired pulse accurately and consistently.

Ultra-high harmonic mode-locking with a micro-fiber knot resonator and Lyot filter.

We report on ultra-high harmonic mode-locking with a repetition rate of up to ∼1 THz by combining a microfiber knot resonator (MKR) and a Lyot filter. The harmonic mode-locked pulses are tunable by changing the diameter of MKR, which agrees well with the theoretical calculation. Our results indicate that the ultrafast pulse generation mechanism is due to the dissipative four-wave mixing mode-locking technique. This work provides a simple and efficient scheme to generate tunable ultrafast pulses with a high repetition rate for various applications, such as THz generation and ultrafast data communication.

Mid-infrared optical switches enabled by metal-organic frameworks for compact high-power nanosecond laser sources at 3 µm.

Pulsed lasers operating in the mid-infrared are of great importance for numerous applications in spectroscopy, medical surgery, laser processing, and communications. In spite of recent advances with mid-infrared gain platforms, the lack of a capable pulse generation mechanism hinders the development of compact mid-infrared pulsed laser source. Here we show that MIL-68(Al) and MIL-68(Fe), which are aluminum- and iron- based metal-organic frameworks (MOFs) with ordered atoms distribution and periodic mesoporous structure, constitute exceptional optical switches for the mid-infrared. We fabricated the MIL-68(Al) and MIL-68(Fe) via hydrothermal method and prepared reflection-type MIL-68(Al)- and MIL-68(Fe)- saturable absorber mirrors (SAMs). By employing the as-prepared SAMs in the laser cavities, we achieved high-power nanosecond Q-switched fiber lasers at 2.8 µm. Especially, the average output power and pulse duration of the MIL-68(Al) Q-switched fiber laser reached 809.1 mW and 567 ns, respectively. To the best of our knowledge, this is the first time to demonstrate that MIL-68(M) can be efficient optical switches for 3-µm mid-IR laser pulses generation. Our findings reveal that MIL-68(M) is promising saturable absorber for compact and high-performance mid-infrared pulsed lasers.

Relationship Between Asperities and Velocity Pulse Generation Mechanism

Near-fault ground motion records often capture instances of pulse-like behavior, where a burst of energy is expressed as large wave amplitude that occur over short time. The pulse-like ground motion can cause serious damage to long-period structures. Using numerical simulations of near-fault ground motions, we analyze the mechanisms involved in the generation of velocity pulses in the 1994 Northridge Earthquake and the 1979 Imperial Valley Earthquake. The degree to which the asperities affect the pulse generation process is investigated by identifying individual velocity pulses from the superposition process of sub-fault ground motions. Pulse indicators Ep and PGVp represent pulse characteristics in the ground motions at the stations located near the epicenter (near-epicenter stations) and the stations located along the forward rupture propagation direction of the asperity (rupture-direction stations), respectively. To observe the effects of the asperities and the spatial relationship between the pulse-like ground motion stations and the asperities, we determine the contribution of the sub-fault motions to the pulse amplitude. Furthermore, we analyze the pulse indicators and the frequency components using simulated ground motions from two different slip distributions. The near-epicenter station ground motions, produced by homogeneous slip distribution, exhibit higher pulse amplitude and more concentrated low-frequency energy than those generated by the inhomogeneous slip distribution. The rupture-direction station ground motions, produced by inhomogeneous slip distribution, present higher pulse amplitude and more concentrated low-frequency energy than those generated by the homogeneous slip distribution. Our analysis reveals that during the fault rupture process, the pulse energy and the pulse amplitude are influenced by both the slip distribution on the fault plane and the spatial relationship between the seismic station and the asperity.

Investigation of the impact characteristics and pulse mechanism of a self-excited aspiration pulsed jet device

In this paper, based on the traditional low-frequency self-excited oscillation pulsed jet device, a self-excited aspiration pulsed jet device is designed. For the structural parameters, including the aspiration capacity, impact characteristics, and pulse generation mechanism, the jet impingement is analyzed experimentally under the aspiration and non-aspiration conditions. It was found that, compared to the non-aspiration condition, the maximum aspiration capacity, the increase of instantaneous impact force, and the obvious pulse period, which is between 1 and 2 s, can be obtained under appropriate structural device parameters. The db10 orthogonal wavelet and the empirical mode decomposition methods can decompose instantaneous impact force into time-varying and fluctuating impact forces. However, under different confining pressures, each method has its own advantages in extracting the time-varying impact force. In addition, after aspiration, the confining pressure and target distance have little effect on the pulse frequency of the time-varying impact force, while higher confining pressure and larger target distance result in smaller pulse amplitude. Under different confining pressures and target distances, after aspiration, the time-average impact force at and near the target center increases, while far away from the target center it decreases. Moreover, after aspiration, the fluctuation amplitude and intensity of the fluctuating impact force increase, and the confining pressure has little effect on the pulse frequency. However, higher confining pressure results in smaller fluctuation amplitude, intensity, and energy spectral density. After aspiration, subsonic and supersonic water flows are formed inside the device. In addition, it was found that there is a relationship between the aspiration capacity, the time-variation pressure of the collision body measuring point, and the impact force. Based on this relation, the pulse generation mechanism of the device is revealed.

Terahertz pulse emission from photoexcited bulk crystals of transition metal dichalcogenides

Multilayer MoS2, MoSe2, and WSe2 crystals were excited with femtosecond optical pulses of various wavelengths. The emitted terahertz (THz) radiation pulses were found to be the most intense at photon energies coinciding with the direct energy gap at the K points of the Brillouin zone of corresponding materials. It was shown that the transition metal dichalcogenides of different dopant type emit THz pulses of opposite polarity, suggesting that the surface field plays a role in THz emission. Nevertheless, the optical pump–THz probe experiments contradicted THz emission observations, demonstrating a decrease in photoconductivity at higher energy quanta. The proposed THz pulse generation mechanism, therefore, assumes the accumulation of excitonic electric dipoles during optical pulse absorption and a fast build-up of the internal electric field inside the samples. This assumption was supported by double optical pulse investigations.

3Pb2-5 Internal vibration of active faults and lateral pulse generation mechanism

3Pb2-5 Internal vibration of active faults and lateral pulse generation mechanism

Filtering input fluctuations in intensity and in time underlies stochastic transcriptional pulses without feedback

Stochastic pulsatile dynamics have been observed in an increasing number of biological circuits with known mechanism involving feedback control and bistability. Surprisingly, recent single-cell experiments in Escherichia coli flagellar synthesis showed that flagellar genes are activated in stochastic pulses without the means of feedback. However, the mechanism for pulse generation in these feedbackless circuits has remained unclear. Here, by developing a system-level stochastic model constrained by a large set of single-cell E. coli flagellar synthesis data from different strains and mutants, we identify the general underlying design principles for generating stochastic transcriptional pulses without feedback. Our study shows that an inhibitor (YdiV) of the transcription factor (FlhDC) creates a monotonic ultrasensitive switch that serves as a digital filter to eliminate small-amplitude FlhDC fluctuations. Furthermore, we find that the high-frequency (fast) fluctuations of FlhDC are filtered out by integration over a timescale longer than the timescale of the input fluctuations. Together, our results reveal a filter-and-integrate design for generating stochastic pulses without feedback. This filter-and-integrate mechanism enables a general strategy for cells to avoid premature activation of the expensive downstream gene expression by filtering input fluctuations in both intensity and time so that the system only responds to input signals that are both strong and persistent.

High-power short-pulse solid-state microlaser with segmented diode pumping

In this study, the mechanism of pulse generation is investigated in a compact laser system based on YAG:Nd3+ with passive Q-switching, which utilizes segmented pumping of the active medium by seven quasicontinuous laser diodes with fiber-optic radiation outputs. The dependence of lasing on the individual and correlative properties of pumping channels is studied in general and upon disabling one or several pumping channels. The maximum output emission energy achieved is 20 mJ for a synchronous pulse with a duration of 3.3 ns. The possibility of obtaining a stable optical breakdown of air using the developed laser is experimentally confirmed, facilitating its practical application in, for example, the ignition of combustible mixtures.

Passively Q-switched near-infrared lasers with bismuthene quantum dots as the saturable absorber

Bismuthene quantum dots (Bi-QDs) were synthesized via the liquid phase exfoliation (LPE) method for the passive Q-switching operation in near-infrared (NIR) region. The nonlinear optical properties of the prepared Bi-QDs were investigated by the open-aperture Z-scan technology. The modulation depths were 18.1% and 5.1% at 1.06 and 1.34 µm, respectively. Based on the Bi-QDs saturable absorber, passively Q-switched Nd:GdVO4 lasers operating at 4F3/2 → 2I11/2 and 4F3/2 → 2I13/2 transitions were demonstrated, showing the wideband optical modulation in NIR regime. For the 4F3/2 → 2I13/2 transition lasing at 1.34 µm, the shortest pulse duration of 155 ns was obtained with a repetition rate of 457 kHz. With respect to the 4F3/2 → 2I11/2 transition at 1.06 µm, the minimum pulse duration was 150 ns with a repetition rate of 424 kHz, leading to a single pulse energy of 261 nJ and a peak power of 1.68 W. In addition, the ground state absorption cross section and the excited state absorption cross section of Bi-QDs were also investigated for the first time. The impact of the excited state lifetime on the output parameters was numerically stimulated by the coupled rate equations. Our work confirmed that the trap state in Bi-QDs played an important role in the pulse generation mechanism.

Ultra-Short Pulse Generation in a Three Section Tapered Passively Mode-Locked Quantum-Dot Semiconductor Laser

We experimentally and theoretically investigate the pulsed emission dynamics of a three section tapered semiconductor quantum dot laser. The laser output is characterized in terms of peak power, pulse width, timing jitter and amplitude stability and a range of outstanding pulse performance is found. A cascade of dynamic operating regimes is identified and comprehensively investigated. We propose a microscopically motivated traveling-wave model, which optimizes the computation time and naturally allows insights into the internal carrier dynamics. The model excellently reproduces the measured results and is further used to study the pulse-generation mechanism as well as the influence of the geometric design on the pulsed emission. We identify a pulse shortening mechanism responsible for the device performance, that is unique to the device geometry and configuration. The results may serve as future guidelines for the design of monolithic high-power passively mode-locked quantum dot semiconductor lasers.

Principles of Designing Air-Driven Hammer with Decoupled Piston for Driving Rods in Soil

Improvability of air-driven pulse-generating mechanisms for operation in mineral mining and construction is discussed. An impact system with two mobile masses incorporated in a common housing is proposed for vibro-percussive driving of structural iron into elastoplastic soil. Experimental prototype of the air hammer with decoupled piston based on the air distribution circuit with elastic valve in the back stroke chamber of the piston is described. The test data of operation cycle of the piston in case of different variants of settings are presented. The possibility to exert influence on the nature and frequency of impacts is demonstrated.

The Gonadotropin-Releasing Hormone Pulse Generator.

The pulsatile release of GnRH and LH secretion is essential for fertility in all mammals. Pulses of LH occur approximately every hour in follicular-phase females and every 2 to 3 hours in luteal-phase females and males. Many studies over the last 50 years have sought to identify the nature and mechanism of the "GnRH pulse generator" responsible for pulsatile LH release. This review examines the characteristics of pulsatile hormone release and summarizes investigations that have led to our present understanding of the GnRH pulse generator. There is presently little compelling evidence for an intrinsic mechanism of pulse generation involving interactions between GnRH neuron cell bodies. Rather, data support the presence of an extrinsic pulse generator located within the arcuate nucleus, and attention has focused on the kisspeptin neurons and their projections to GnRH neuron dendrons concentrated around the median eminence. Sufficient evidence has been gathered in rodents to conclude that a subpopulation of arcuate kisspeptin neurons is, indeed, the GnRH pulse generator. Findings in other species are generally compatible with this view and suggest that arcuate/infundibular kisspeptin neurons represent the mammalian GnRH pulse generator. With hindsight, it is likely that past arcuate nucleus multiunit activity recordings have been from kisspeptin neurons. Despite advances in identifying the cells forming the pulse generator, almost nothing is known about their mechanisms of synchronicity and the afferent hormonal and transmitter modulation required to establish the normal patterns of LH pulsatility in mammals.

Delayed loss of stability due to the slow passage through Hopf bifurcations in reaction-diffusion equations.

This article presents the delayed loss of stability due to slow passage through Hopf bifurcations in reaction-diffusion equations with slowly-varying parameters, generalizing a well-known result about delayed Hopf bifurcations in analytic ordinary differential equations to spatially-extended systems. We focus on the Hodgkin-Huxley partial differential equation (PDE), the cubic Complex Ginzburg-Landau PDE as an equation in its own right, the Brusselator PDE, and a spatially-extended model of a pituitary clonal cell line. Solutions which are attracted to quasi-stationary states (QSS) sufficiently before the Hopf bifurcations remain near the QSS for long times after the states have become repelling, resulting in a significant delay in the loss of stability and the onset of oscillations. Moreover, the oscillations have large amplitude at onset, and may be spatially homogeneous or inhomogeneous. Space-time boundaries are identified that act as buffer curves beyond which solutions cannot remain near the repelling QSS, and hence before which the delayed onset of oscillations must occur, irrespective of initial conditions. In addition, a method is developed to derive the asymptotic formulas for the buffer curves, and the asymptotics agree well with the numerically observed onset in the Complex Ginzburg-Landau (CGL) equation. We also find that the first-onset sites act as a novel pulse generation mechanism for spatio-temporal oscillations.

Generation of a Periodic Sequence of High-Power Ultrashort Pulses in a Chain of Coupled Backward-Wave and Traveling-Wave Tubes Operating in the Regimes of Amplification and Nonlinear Kompfner Suppression

We have studied the dynamics of an electronic microwave generator with backward-wave and traveling-wave tubes connected in the feedback circuit and operating in the regimes of amplification and nonlinear Kompfner absorption, respectively. It is shown that radiation generated in such a system can have the form of a periodic sequence of ultrashort pulses. The studied mechanism of pulse generation is analogous to the method of passive mode locking, which is widely used in laser physics.

High-repetition-rate, multi-pulse all-normal-dispersion fiber laser.

In this Letter, a fiber laser that exploits the dissipative Faraday instability as a pulse-generating mechanism is presented, and its dynamics are studied numerically. The proposed laser operates in the all-normal-dispersion regime and produces a train of quasi-parabolic pulses, with a repetition rate that can be controlled depending on the cavity dispersion and nonlinearity, ranging from 10 to 50GHz. It exploits a lumped amplification scheme, which can be potentially realized with rare-earth gain media. The issues concerning the stability of the pulses are discussed, and the differences with similar pulsed lasers are highlighted. In particular, the transition from the ordered multi-pulse regime proposed here to the random pulse operation mode already studied in the literature is discussed.

Generation of periodic high-power ultrashort pulse sequences in a chain of coupled traveling-wave tubes operating in the regimes of amplification and nonlinear Kompfner suppression

We have studied the dynamics of an electron microwave oscillator with a feedback loop containing two coupled traveling-wave tubes, the first operating in the regime of amplification and the second in the regime of nonlinear Kompfner absorption. It is established that oscillations generated in this system can take the form of a periodic sequence of ultrashort pulses. The proposed mechanism of pulse generation is analogous to the well-known method of passive mode locking.

Dynamic backcalculation with different load-time histories

This paper focused attention to the falling weight deflectometer (FWD) load-time history. For a commonly used device, it studied the pulse generation mechanism and the influence of different load histories on backcalculation results. In this connection, a semi-analytic impact theory was first introduced for realistically simulating FWD pulse generation. Then a newly developed finite-element code was presented for FWD interpretation; the code is capable of addressing dynamics, time-dependent layer properties, and quasi-nonlinear behaviour. Both new developments were demonstrated for an experimental dataset that resulted from operating an FWD with different loading configurations. It was found that backcalculated parameters are sensitive to the FWD pulse features. Consequently, it is recommended that, whenever advanced pavement characterisation is sought, experimental attention should be placed on generating diverse FWD pulse histories. Collectively, the resulting deflection histories will contain pertinent constitutive information for supporting the calibration of more complex pavement models.