Burst Length Research Articles

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits

Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison ®, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

A multi-modal composition of the late Na+ current in human ventricular cardiomyocytes

We reported an ultraslow late Na+ current (INaL) in ventricular cardiomyocytes of human hearts. INaL has been implicated in regulation of action potential duration in normal hearts and repolarization abnormalities in failing hearts. We have also identified sodium channel (NaCh) gating modes including bursts (BM) and late scattered openings (LSM) that together comprise INaL; however, the contribution of these gating modes to Na+ current (INa) remains unknown. In the present study, the late NaCh activity was recorded, analyzed, and modeled for heterologously expressed NaCh, Nav1.5, and for the native NaCh of ventricular mid-myocardial cardiomyocytes from normal and failing hearts. We found that LSM gating was significantly slower in failing compared to normal myocytes and Nav1.5 (tau=474+/-10 vs. 299+/-9, and 229+/-12 ms, m+/-SEM; P<0.05, n=5-6). Total burst length of BM decreased with depolarization and was larger in failing compared to normal myocytes and Nav1.5. A complete INa decay was then numerically approximated as composed of NaCh populations operating in three gating modes described by separate Markov kinetic schemes: transient mode (TM), LSM, and BM. The populations of NaCh operating in each gating mode were estimated as 79.8% for TM, 20% for LSM, and 0.2% for BM, yielding an apparent four-exponential INa decay at -30 mV (maximum INa) (tau i approximately 0.4, 4, 50, and 500 ms). Whole-cell recordings confirmed the existence of all four predicted components. The model also predicted voltage and temperature dependence of INaL as well as INaL increase and slower decay in failing hearts and acceleration by amiodarone. The early phase of Na+ current decay (<40 ms) involves all three NaCh gating modes, the intermediate phase (from 40 to 300 ms) is produced by BM+LSM, although the contribution of BM decreases with depolarization, and ultra-late decay (>300 ms) is determined solely by LSM. The concept of multi-mode composition for INaL provides a new rationale for INaL modulation by factors such as voltage, temperature, pharmacological agents, and pathological conditions.

High-resolution pulse shaper based on arrays of digital micromirrors

We describe an optical Fourier transform pulse shaper based on a combination of a diffraction grating and a reconfigurable array of digital micromirrors. The pulse shaper allows for adjustment of separation between consecutive pulses within a pulse burst and the length of the burst. Pulse separation, burst length, and number of pulses can be dynamically reconfigured by changing the periodic pattern imposed to the array of digital micromirrors. Experimental results on binary intensity modulation are in excellent agreement with basic design relations describing the spectral and temporal characteristics of the pulse shaper.

Dynamic traffic grooming in optical burst-switched networks

In this paper, we address the problem of data-burst grooming in optical burst-switched (OBS) networks. In OBS networks, IP packets with the same edge-node destination are assembled into larger packets called data bursts. Depending on the core node's switching technology, data bursts are required to have a minimum length. On the other hand, each IP packet in a burst has a time delay constraint, called maximum end-to-end delay, which determines the upper time limit before which the packet must reach its destination. Thus, a data burst cannot wait indefinitely until a sufficient number of IP packets are assembled and the minimum burst length requirement is met. In order to satisfy the packet maximum end-to-end delay requirement, many bursts will be timed out and released before they reach the minimum-length requirement. Under such circumstances, padding overhead must be added to these short bursts, called sub-bursts. Excessive padding results in high overhead and high data-burst blocking probability. One approach to minimize the amount of padding overhead, while maintaining the end-to-end delay requirement of IP packets, is to groom multiple sub-bursts together. That is, sub-bursts with different destinations are aggregated together at the edge node and transmitted as a single burst until they are separated at some downstream node. In this paper, we present an edge-node architecture enabling burst-grooming capability. We also develop two basic grooming approaches, namely No routing overhead (NoRO) and minimum total overhead (MinTO). Through a comprehensive simulation study, we show that, in general, our proposed grooming algorithms can significantly improve the performance compared to the case of no grooming. However, careful considerations must be given to network-loading conditions and the number of sub-bursts allowed to be groomed together. We show that although simple greedy algorithms can reduce network overhead, they may alter the traffic characteristics and increase its burstiness, resulting in high packet blocking probability.

Scalable performance evaluation of a hybrid optical switch

This paper provides new loss models for a hybrid optical switch (HOS) combining optical circuit switching (OCS) and optical burst switching (OBS). Exact blocking probabilities are computed when 1) no priority is given to either circuits or bursts and 2) circuits are given preemptive priority over bursts. Because it is difficult to exactly compute in realistic scenarios, computationally scalable approximations are derived for the blocking probability. The sensitivity of the analytical results to burst length and circuit holding-time distributions is quantified by simulation. It is demonstrated how the proposed approximations can be used for multiplexing-gain evaluation of a hybrid switch. In addition, the extension of the proposed single-node model to a network model composed of OCS, OBS, and hybrid switches is outlined.

The Effects of Nonnutritive Sucking and Oral Support on the Feeding Efficiency of Preterm Infants

The purpose of this study is to describe the influence of oral support and nonnutritive sucking (NNS) across time on the feeding efficiency of preterm infants. The study was conducted as a three-group repeated-observation control group design. One hundred fifty-six infants were included in the analysis. Repeated-measures analysis of variance was performed at baseline, immediately after a 1-week intervention, and 7 days postintervention on the formula intake at 5 minutes, length of feeding, bursts, pauses, and pause duration. It was concluded that oral support and NNS are beneficial for preterm infants and that both interventions have immediate and continuing effects on the amount of formula taken in the first 5 minutes of feeding. The effects on sucking pattern characteristics are mixed with continuing effects noted on the number and length of bursts after the use of oral support and NNS but not immediately after the intervention.

Fairness issue and monitor-based algorithm in optical burst switching networks

Optical burst switching (OBS) is a new paradigm proposed to efficiently support the ever-growing broadband traffic over WDM networks. In this paper, unfairness due to path length priority effect (PLPE) and burst length priority effect (BLPE) is identified in OBS networks. We propose three algorithms: M-PLPE, M-BLPE and M-PBLPE to alleviate unfairness due to PLPE, BLPE, and simultaneously PLPE and BLPE, respectively. These algorithms are all built upon a general fairness framework which we call the monitoring group drop probability (MGDP) framework for alleviating unfairness. In addition, we also propose an adaptive fairness searching algorithm, OFSA (Optimal Fairness Searching Algorithm), which can achieve optimal performance within a range of fairness objectives. Simulation results show that the new algorithms can achieve a desired fairness metric for both BLPE and PLPE, while minimizing the performance tradeoff. It is also demonstrated that the contributed fairness mechanisms actually improves throughput at high loads. In addition, none of algorithms require the specification of a fuzzy threshold. All thresholds used with the contributed algorithms are systematically updated using well thought out formulas with no fuzzy parameters required.

Contrasting Roles of Protein Kinase C in Induction Versus Suppression of Group I mGluR-Mediated Epileptogenesis In Vitro

Activation of group I metabotropic glutamate receptors (mGluRs) elicits persistent ictaform discharges in guinea pig hippocampal slices, providing an in vitro model of epileptogenesis. The induction of these persistent ictaform bursts is prevented by l-cysteine sulfinic acid (CSA), an agonist at phospholipase D (PLD)-coupled mGluRs. Studies described herein examined the role of protein kinase C (PKC) in both the group I mGluR-mediated induction and CSA-mediated suppression of this form of epileptogenesis. Intracellular recordings were performed from CA3 stratum pyramidale and synchronized burst length was monitored. In the presence of 50 microM picrotoxin, a gamma-aminobutyric acid type A antagonist, 250- to 500-ms synchronized bursts were elicited. (S)-3,5-Dihydroxyphenylglycine (DHPG, 50 microM), an agonist at group I mGluRs, increased the burst length to 1-3 s in duration, a change that persisted after agonist washout. This persistent change in burst length was elicited in the presence of 10 microM chelerythrine, a PKC inhibitor, indicating that DHPG-induced epileptogenesis is PKC independent. However, although PLD activation with CSA (100 microM) was highly effective at suppressing group I mGluR-mediated induction of burst prolongation, CSA application in the presence of chelerythrine was no longer effective and resulted in the expression of persistent ictaform bursts. These data suggest that CSA-mediated suppression of group I mGluR-induced epileptogenesis is PKC dependent. We propose that CSA mediates its effect by PLD-driven activation of PKC, which may desensitize the phospholipase C-linked group I mGluRs and thereby prevent group I mGluR-induced epileptogenesis.

Burst characteristics of daily jaw muscle activity in juvenile rabbits

Muscle activation varies with different behaviors and can be quantified by the level and duration of activity bursts. Jaw muscles undergo large anatomical changes during maturation, which are presumably associated with changes in daily muscle function. Our aim was to examine the daily burst number, burst length distribution and duty time (fraction of the day during which a muscle was active) of the jaw muscles of juvenile male rabbits (Oryctolagus cuniculus). A radio-telemetric device was implanted to record muscle activity continuously from the digastric, superficial and deep masseter, medial pterygoid and temporalis during maturation week 9-14. Daily burst characteristics and duty times were determined for activations, including both powerful and non-powerful motor behavior. All muscles showed constant burst numbers, mean burst lengths and duty times during the recording period. Including all behavior, the temporalis showed significantly larger daily burst numbers (205,000) and duty times (18.2%) than the superficial and deep masseter (90,000; 7.5%). Burst numbers and duty times were similar for the digastric (120,000; 11.1%) and medial pterygoid (115,000; 10.4%). The temporalis and deep masseter showed many short low activity bursts (0.05 s), the digastric showed many long bursts (0.09 s). For activations during powerful behaviors the superficial masseter and medial pterygoid had the largest burst numbers and duty times. Both muscles showed similar burst characteristics for all activation levels. It was concluded that activation of the jaw muscles is differently controlled during powerful and non-powerful motor behaviors and the functional organization of motor control patterns does not vary from 9 to 14 weeks of age.

A Detailed Analysis and Performance Comparison of Wavelength Reservation Schemes for Optical Burst Switched Networks?

We present a detailed analysis of the JIT, JET, and Horizon wavelength reservation schemes for optical burst switched (OBS) networks. Our analysis accounts for several important parameters, including the burst offset length, and the optical switching and hardware processing overheads associated with bursts as they travel across the network. The contributions of our work include: (i) analytical models of JET and Horizon (on a single OBS node) that are more accurate than previously published ones, and which are valid for general burst length and offset length distributions; (ii) the determination of the regions of parameter values in which a more complex reservation scheme reduces to a simpler one; and (iii) a new reservation scheme, JIT+, which is as simple to implement as JIT, but whose performance tracks that of Horizon and JET. We compare the performance of the four wavelength reservation schemes on a single OBS node, as well as on a path of OBS nodes with cross traffic, under various sets of parameter values. Our major finding is that, under reasonable assumptions regarding the current and future state-of-the-art in optical switch and electronic hardware technologies, the simplicity of JIT and JIT+ seem to outweigh any performance benefits of Horizon and JET.

Daily number and lengths of activity bursts in rabbit jaw muscles

Muscle activity has predominantly been studied for specific motor tasks not necessarily representative of normal daily behaviour. The few studies that have examined daily muscle use have quantified this by duty time, merging all levels of muscle activity. Muscle activity can also be characterized by the number, duration and level of bursts. The purpose of this study was to characterize, for various levels of muscle activity, the daily masseter and digastric actions in the rabbit. Characterization was realized by quantification of duty time (summed length of all bursts as a percentage of total time), number of bursts and distribution of burst lengths. A telemetric device was implanted in the two muscles of six rabbits, ensuring the recording of their jaw muscle activities while they moved freely. The continuously transmitted signals over 1 day were analysed. The results showed that (i) more than 100,000 bursts per day exceeded the 2% level of the maximum muscle activity in both muscles, whereas fewer than 100 bursts per day exceeded the 90% level; and (ii) the digastric muscle exhibited a significantly higher duty time than the masseter (respectively, 23% and 14% for activities exceeding the 2% level), which was mainly caused by the on average longer burst lengths at the lowest levels. The characterization of muscle activity in daily burst number and distribution of burst lengths exceeding various activity levels provides valuable information on motor control and enables further investigation of the adaptive capacity of muscles.

Low rate TCP denial-of-service attack detection at edge routers

Low rate TCP denial-of-service attacks are a new type of DoS attacks that are carefully orchestrated to exploit the fixed minimum TCP RTO property and thereby deny services to legitimate users. This type of attacks is different from traditional flood-based attacks and hence conventional solutions to detect these attacks are not applicable. We propose a novel approach to detect these attack flows at edge routers. A flow exhibiting a periodic pattern is marked malicious if its burst length is greater than or equal to RTTs of other connections with the same server and its time period is equal to the fixed minimum RTO. A carefully designed light weight data structure is proposed to store the necessary flow history at edge routers. Simulation results show that such flows can be detected by our proposed approach, which does not require any modification to TCP congestion control algorithms like randomizing the fixed minimum RTO.

A human congenital myasthenia‐causing mutation (ɛL78P) of the muscle nicotinic acetylcholine receptor with unusual single channel properties

A mutation in the epsilon subunit of the human nicotinic acetylcholine receptor (epsilonL78P) is known to cause a congenital slow channel myasthenic syndrome. We have investigated the changes in receptor function that result in the mutant receptor producing prolonged endplate currents, and consequent muscle damage. The rate constants for channel gating and for the binding and dissociation of acetylcholine were investigated by analysis of single ion channel recordings. A conventional mechanism with two non-equivalent binding sites, and variations upon this mechanism, were fitted to data using a maximum likelihood method that uses the Hawkes-Jalali-Colquhoun (HJC) treatment of missed brief events. The mutant receptor produced prolonged activations, bursts of openings that cause a slow decay of simulated synaptic currents. The main reason for the longer bursts of openings seen with mutant receptor was a decrease in the rate of ACh dissociation from diliganded receptors, though the lifetime of individual openings was somewhat increased too. As well as producing long bursts, the mutant receptor also produced many very short openings, though these carry little current. The burst structure for the mutant receptor at low ACh concentration is unusual in that most long bursts appear to start in a very brief monoliganded open state that then usually binds another ACh molecule to produce a long diliganded activation. The first opening is so short that it will usually be missed (together with the shut time that follows it), so the true burst length is likely to be underestimated.

Aggravation of Absence Seizures by Carbamazepine in a Genetic Rat Model Does Not Induce Neuronal c-Fos Activation

The mechanisms underlying carbamazepine aggravation of absence seizures are uncertain but are thought to involve enhancement of neuronal activity within the thalamocortical circuitry. We used c-Fos immunohistochemistry (cFos-ir) to examine patterns of neuronal activation and the relationship to seizure expression following administration of carbamazepine in a rat model of absence epilepsy (Genetic Absence Epilepsy Rats of Strasbourg, GAERS). Female ovariectomized GAERS implanted with extradural EEG electrodes received either 20 mg/kg carbamazepine or vehicle IP. Seizure expression was quantified by measuring the total number and duration of spike-wave discharges (SWD) and with the individual burst discharge lengths over a 90-minute EEG. This was correlated with cFos-ir in thalamocortical slices from rats killed 180 minutes after carbamazepine administration. Carbamazepine-treated rats (n = 5) had a significantly greater total duration of SWD than vehicle-treated rats (17.9% versus 8.8%, P = 0.04). Despite this aggravation of seizures, the level of cFos-ir did not differ between the treatment groups. A positive correlation was found between cFos-ir in the reticularis thalami (Rt) and the total seizure duration (R = 0.66, P = 0.04) and mean burst length (R = 0.68, P = 0.03) but not total number of seizures. The lack of difference in cFos activation patterns between carbamazepine and vehicle-treated animals suggests that the mechanism for carbamazepine aggravation of absence seizures may not involve neuronal activation but rather enhanced neuronal synchronization. The association between increased neuronal activation in the Rt and seizure burden in GAERS provides further support for the critical role of this structure in the maintenance, but not initiation, of absence seizure activity.

Spatial Structure of Complex Cell Receptive Fields Measured with Natural Images

Neuronal receptive fields (RFs) play crucial roles in visual processing. While the linear RFs of early neurons have been well studied, RFs of cortical complex cells are nonlinear and therefore difficult to characterize, especially in the context of natural stimuli. In this study, we used a nonlinear technique to compute the RFs of complex cells from their responses to natural images. We found that each RF is well described by a small number of subunits, which are oriented, localized, and bandpass. These subunits contribute to neuronal responses in a contrast-dependent, polarity-invariant manner, and they can largely predict the orientation and spatial frequency tuning of the cell. Although the RF structures measured with natural images were similar to those measured with random stimuli, natural images were more effective for driving complex cells, thus facilitating rapid identification of the subunits. The subunit RF model provides a useful basis for understanding cortical processing of natural stimuli.

Variations in phenology and growth of European white birch (Betula pendula) clones

Phenology can have a profound effect on growth and climatic adaptability of northern tree species. Although the large interannual variations in dates of bud burst and growth termination have been widely discussed, little is known about the genotypic and spatial variations in phenology and how these sources of variation are related to temporal variation. We measured bud burst of eight white birch (Betula pendula Roth) clones in two field experiments daily over 6 years, and determined the termination of growth for the same clones over 2 years. We also measured yearly height growth. We found considerable genetic variation in phenological characteristics among the birch clones. There was large interannual variation in the date of bud burst and especially in the termination of growth, indicating that, in addition to genetic effects, environmental factors have a strong influence on both bud burst and growth termination. Height growth was correlated with timing of growth termination, length of growth period and bud burst, but the relationships were weak and varied among years. We accurately predicted the date of bud burst from the temperature accumulation after January 1, and base temperatures between +2 and -1 degrees C. There was large clonal variation in the duration of bud burst. Interannual variation in bud burst may have important consequences for insect herbivory of birches.

The Burst Error Correcting Capabilities of a Simple Array Code

We propose a simple decoder for a widely used array code, known as the EVENODD code, which is originally designed to correct phased burst errors, to make it useful for correcting nonphased errors. The proposed scheme is capable of correcting almost all bursts up to a certain length. We show that the failure rate is sufficiently small and approaches zero as the block length increases. The redundancy of the code is twice the maximal burst length, which is a lower bound for the redundancy of a true burst-error-correcting code. Both the encoder and the decoder have very low complexity, both in terms of number of operations and in terms of computer code size

Optical observations of acoustical radiation force effects on individual air bubbles

Previous studies dealing with contrast agent microbubbles have demonstrated that ultrasound (US) can significantly influence the movement of microbubbles. In this paper, we investigated the influence of the acoustic radiation force on individual air bubbles using high-speed photography. We emphasize the effects of the US parameters (pulse length, acoustic pressure) on different bubble patterns and their consequences on the translational motion of the bubbles. A stream of uniform air bubbles with diameter ranging from 35 microm to 79 microm was generated and insonified with a single US pulse emitted at a frequency of 130 kHz. The bubble sizes have been chosen to be above, below, and at resonance. The peak acoustic pressures used in these experiments ranged from 40 kPa to 120 kPa. The axial displacements of the bubbles produced by the action of the US pulse were optically recorded using a high-speed camera at 1 kHz frame rate. The experimental results were compared to a simplified force balance theoretical model, including the action of the primary radiation force and the fluid drag force. Although the model is quite simple and does not take into account phenomena like bubble shape oscillations and added mass, the experimental findings agree with the predictions. The measured axial displacement increases quasilinearly with the burst length and the transmitted acoustic pressure. The axial displacement varies with the size and the density of the air bubbles, reaching a maximum at the resonance size of 48 microm. The predicted displacement values differ by 15% from the measured data, except for resonant bubbles for which the displacement was overestimated by about 40%. This study demonstrates that even a single US pulse produces radiation forces that are strong enough to affect the bubble position.

Frequency-dependent depletion of secretory vesicle pools modulates bursting in vasopressin neurones of the rat supraoptic nucleus

When stimulated, vasopressin neurones discharge lengthy, repeating bursts of action potentials. An increase in the stimulus strength causes both a lengthening of the bursts’ active phase and an increase in the intra-burst firing frequency. Here we extend our earlier model (P. Roper, J. Callaway, W. Armstrong. J. Neurosci. 24(20) (2004) 4831.) for phasic bursting at a constant stimulus. We show that an increase in burst length could be due to a reduction of the co-secretion of an inhibitory factor, dynorphin, and we propose this to be caused by a frequency-dependent depletion of the pool of secretory vesicles.

Performance Modeling of Optical-Burst Switching With Fiber Delay Lines

We develop analytical models to evaluate the performance of optical-burst switch (OBS) architectures employing fiber delay lines (FDLs) as optical buffers to reduce burst-loss probability. The performance of such architectures cannot be captured accurately using traditional queueing models, since FDLs behave fundamentally differently from conventional electronic buffers. We formulate a Markovian model to evaluate the system performance when the burst-arrival process is Poisson and the burst lengths are exponentially distributed under an idealized model of FDL behavior. The model accurately captures both the balking and deterministic delay properties of FDLs, but the complexity of the model makes it infeasible for solving problems of practical interest. By considering approximations of the model in the regimes of short and long FDLs, we develop relatively simple closed-form expressions that can be used for dimensioning OBS architectures. We also extend the approximate model to include the impact of FDL delay granularity. We present numerical results that validate our modeling approach and demonstrate that significant performance gains in optical-burst switching are achievable when FDLs are employed as optical buffers.