bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of pacing modality on noninvasive assessment of heart rate dependency of indices of large artery function
Authors: Tan Isabella , Kiat Hosen , Barin Edward , Butlin Mark , Avolio Alberto P.
Published: July 2016

Studies investigating the relationship between heart rate (HR) and arterial stiffness or wave reflections have commonly induced HR changes through in situ cardiac pacing. Although pacing produces consistent HR changes, hemodynamics can be different with different pacing modalities. Whether the differences affect the HR relationship with arterial stiffness or wave reflections is unknown. In the present study, 48 subjects [mean age, 78 ± 10 (SD), 9 women] with in situ cardiac pacemakers were paced at 60, 70, 80, 90, and 100 beats per min under atrial, atrioventricular, or ventricular pacing. At each paced HR, brachial cuff-based pulse wave analysis was used to determine central hemodynamic parameters, including ejection duration (ED) and augmentation index (AIx). Wave separation analysis was used to determine wave reflection magnitude (RM) and reflection index (RI). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Pacing modality was found to have significant effects on the HR relationship with ED ( P = 0.01), central aortic pulse pressure ( P = 0.01), augmentation pressure ( P < 0.0001), and magnitudes of both forward and reflected waves ( P = 0.05 and P = 0.003, respectively), but not cfPWV ( P = 0.57) or AIx ( P = 0.38). However, at a fixed HR, significant differences in pulse pressure amplification ( P < 0.001), AIx ( P < 0.0001), RM ( P = 0.03), and RI ( P = 0.03) were observed with different pacing modalities. These results demonstrate that although the HR relationships with arterial stiffness and systolic loading as measured by cfPWV and AIx were unaffected by pacing modality, it should still be taken into account for studies in which mixed pacing modalities are present, in particular, for wave reflection studies.
Using devices to upregulate nonnutritive swallowing in typically developing infants
Authors: Hegyi Szynkiewicz Sarah , Mulheren Rachel W. , Palmore Kathryn W. , O'Donoghue Cynthia R. , Ludlow Christy L.
Published: July 2016

The role of various sensory stimuli for stimulating swallowing in infants may be of importance for assisting infants to develop oral feeding. We evaluated the swallowing mechanism response to two devices for increasing the rate of nonnutritive swallowing in two typically developing infant age groups, ages 2–4 mo and 7–9 mo. One device was a pacifier familiar to the infant; the other was a small vibrator placed on the skin overlying the thyroid cartilage. The rate of nonnutritive swallowing while infants were awake was compared in three 10-min conditions: at rest without stimulation (spontaneous); during nonnutritive sucking with a pacifier; and over 10 min containing 18 epochs of vibratory stimulation for 10 s each. To assess whether vibration on the throat over the laryngeal area altered respiration, the mean cycle length was compared between 10-min intervals either containing vibratory stimulation or without stimulation at rest. Both the pacifier and laryngeal vibration stimulation doubled the rate of swallowing in the infants with a mean age of 3 mo 16 days and infants with a mean age of 8 mo 8 days. No differences occurred in the mean respiratory cycle length between intervals with and without vibration in either age group. Results suggest that nonnutritive sucking, vibration, or both might be beneficial in enhancing swallowing in young infants. Because vibration on the neck would not interfere with oral transfer of liquid, it might provide additional stimulation for swallowing during oral feeding. Both stimulation types should be evaluated for enhancing swallowing in infants with immature swallowing skills.
Single-Neuron Analysis of Human Thalamus in Patients With Intention Tremor and Other Clinical Signs of Cerebellar Disease
Authors: Lenz F. A. , Jaeger C. J. , Seike M. S. , Lin Y. C. , Reich S. G.
Published: July 2016

Tremor that occurs as a result of a cerebellar lesion, cerebellar tremor, is characteristically an intention tremor. Thalamic activity may be related to cerebellar tremor because transmission of some cerebellar efferent signals occurs via the thalamus and cortex to the periphery. We have now studied thalamic neuronal activity in a cerebellar relay nucleus (ventral intermediate—Vim) and a pallidal relay nucleus (ventralis oral posterior—Vop) during thalamotomy in patients with intention tremor and other clinical signs of cerebellar disease (tremor patients). The activity of single neurons and the simultaneous electromyographic (EMG) activity of the contralateral upper extremity in tremor patients performing a pointing task were analyzed by spectral cross-correlation analysis. EMG spectra during intention tremor often showed peaks of activity in the tremor-frequency range (1.9–5.8 Hz). There were significant differences in thalamic neuronal activity between tremor patients and controls. Neurons in Vim and Vop had significantly lower firing rates in tremor patients than in patients undergoing thalamic surgery for pain (pain controls). Other studies have shown that inputs to Vim from the cerebellum are transmitted through excitatory connections. Therefore the present results suggest that tremor in these tremor patients is associated with deafferentation of the thalamus from cerebellar efferent pathways. The thalamic X EMG cross-correlation functions were studied for cells located in Vim and Vop. Neuronal and EMG activity were as likely to be significantly correlated for cells in Vim as for those in Vop. Cells in Vim were more likely to have a phase lag relative to EMG than were cells in Vop. In monkeys, cells in the cerebellar relay nucleus of the thalamus, corresponding to Vim, are reported to lead movement during active oscillations at the wrist. In view of these monkey studies, the present results suggest that cells in Vim are deafferented and have a phase lag relative to tremor that is not found in normal active oscillations. The difference in phase of thalamic spike X EMG activity between Vim and Vop may contribute to tremor because lesions of pallidum or Vop are reported to relieve cerebellar tremor.
Two Different Mechanisms Underlie Reversible, Intrinsic Optical Signals in Rat Hippocampal Slices
Authors: Fayuk Dmitriy , Aitken Peter G. , Somjen George G. , Turner Dennis A.
Published: July 2016

Intrinsic optical signals (IOSs) induced by synaptic stimulation and moderate hypotonic swelling in brain tissue slices consist of reduced light scattering and are usually attributed to cell swelling. During spreading depression (SD), however, light-scattering increases even though SD has been shown to cause strong cell swelling. To understand this phenomenon, we recorded extracellular voltage, light transmission (LT), which is inversely related to light scattering, and interstitial volume (ISV) simultaneously from the same site (stratum radiatum of CA1) in both interface and submerged hippocampal slices. As expected, moderate lowering of bath osmolarity caused concentration-dependent shrinkage of ISV and increase in LT, while increased osmolarity induced opposite changes in both variables. During severe hypotonia, however, after an initial increase of LT, the direction of the IOS reversed to a progressive decrease in spite of continuing ISV shrinkage. SD caused by hypotonia, by microinjection of high-K+ solution, or by hypoxia, was associated with a pronounced LT decrease, during which ISV shrinkage indicated maximal cell swelling. If most of the extracellular Cl− was substituted by the impermeant anion methylsulfate and also in strongly hypertonic medium, the SD-related decrease in LT was suppressed and replaced by a monotonic increase. Nevertheless, the degree of ISV shrinkage was similar in low and in normal Cl− conditions. The optical signals and ISV changes were qualitatively identical in interface and submerged slices. We conclude that there are at least two mechanisms that underlie reversible optical responses in hippocampal slices. The first mechanism underlies light-scattering decrease (hence enhancing LT) when ISV shrinks (cell swelling) under synaptic stimulation and mild hypotonia. Similarly, as result of this mechanism, expansion of ISV (cell shrinkage) during mild hypertonia leads to an increased light scattering (and decreased LT). Thus optical signals associated with this first mechanism show expected cell-volume changes and are linked to either cell swelling or shrinkage. A different mechanism causes the light-scattering increase (leading to a LT decrease) during severe hypotonia and various forms of SD but with a severely decreased ISV. This second mechanism may be due to organelle swelling or dendritic beading but not to cell-volume increase. These two mechanisms can summate, indicating that they are independent in origin. Suppression of the SD-related light-scattering increase by lowering [Cl−]o or severe hypertonia unmasks the underlying swelling-related scattering decrease. The simultaneous IOS and ISV measurements clearly distinguish these two mechanisms of optical signal generation.
Changes in Crossed Spinal Reflexes After Peripheral Nerve Injury and Repair
Authors: Valero-Cabré Antoni , Navarro Xavier
Published: July 2016

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.
Superior Colliculus Activity Related to Concurrent Processing of Saccade Goals in a Visual Search Task
Authors: McPeek Robert M. , Keller Edward L.
Published: July 2016

Saccades are typically separated by inter-saccadic fixation intervals (ISFIs) of ≥125 ms. During this time, the saccadic system selects a goal and completes the preparatory processes required prior to executing the subsequent movement. However, in tasks in which competing stimuli are presented, two sequentially executed movements to different goals can be separated by much shorter ISFIs. This suggests that the saccadic system is capable of completing many of the preparatory requirements for a second saccade concurrently with the execution of an initial movement. We recorded single neurons in the superior colliculus (SC) during rapid saccade sequences made by rhesus monkeys performing a search task. We found that during the execution of an initial saccade, activity related to the goal of a quickly following second saccade can be simultaneously maintained in the SC motor map. This activity appears to signal the selection or increased salience of the second saccade goal even before the initial saccade has ended. For movements separated by normal ISFIs (≥125 ms), we did not observe activity related to concurrent processing, presumably because for these longer ISFI responses, the goal of the second saccade is not selected until after the end of the first saccade. These results indicate that, at the time of an initial saccade, the SC does not necessarily act as a strict winner-take-all network. Rather it appears that the salience of a second visual goal can be simultaneously maintained in the SC. This provides evidence that selection or preparatory activity related to the goal of a second saccade can overlap temporally with activity related to an initial saccade and indicates that such concurrent processing is present even in a structure which is fairly close to the motor output.
Synaptic Activity in Chronically Injured, Epileptogenic Sensory-Motor Neocortex
Authors: Li Huifang , Prince David A.
Published: July 2016

We recorded spontaneous and evoked synaptic currents in pyramidal neurons of layer V in chronically injured, epileptogenic neocortex to assess changes in the efficacy of excitatory and inhibitory neurotransmission that might promote cortical hyperexcitability. Partial sensory-motor neocortical isolations with intact blood supply (“undercuts”) were made in 20 rats on postnatal day 21–25 and examined 2–6 wk later in standard brain slice preparations using whole cell patch-clamp techniques. Age-matched, uninjured naive rats ( n = 20) were used as controls. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (s- and mEPSCs; s- and mIPSCs) were recorded using patch-clamp techniques. The average frequency of s- and mEPSCs was significantly higher, while that of s- and mIPSCs was significantly lower in neurons of undercuts versus controls. The increased frequency of excitatory events was due to an increase in both s- and mEPSC frequency, suggesting an increased number of excitatory contacts and/or increased release probability at excitatory terminals. No significant difference was observed in 10–90% rise time of these events. The input-output slopes of fast, short-latency, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor-mediated components of evoked EPSCs were steeper in undercuts than in controls. The peak amplitude of the AMPA/KA component of EPSCs evoked by supra-threshold stimuli was significantly greater in the partially isolated neocortex. In contrast, the N-methyl-d-aspartate receptor-mediated component of evoked EPSCs was not significantly different in neurons of injured versus control cortex, suggesting that the increased AMPA/KA component was due to postsynaptic alterations. Results support the conclusion that layer V pyramidal neurons receive increased AMPA/KA receptor-mediated excitatory synaptic drive and decreased GABAAreceptor-mediated inhibition in this chronically injured, epileptogenic cortex. This shift in the balance of excitatory and inhibitory synaptic activation of layer V pyramidal cells toward excitation might be maladaptive and play a critical role in epileptogenesis.
Comparison of Human Ocular Torsion Patterns During Natural and Galvanic Vestibular Stimulation
Authors: Schneider Erich , Glasauer Stefan , Dieterich Marianne
Published: July 2016

Galvanic vestibular stimulation (GVS) is reported to induce interindividually variable tonic ocular torsion (OT) and superimposed torsional nystagmus. It has been proposed that the tonic component results from the activation of otolith afferents. We tested our hypothesis that both the tonic and the phasic OT are mainly due to semicircular canal (SCC) stimulation by examining whether the OT patterns elicited by GVS can be reproduced by pure SCC stimulations. Using videooculography we measured the OT of six healthy subjects while two different stimuli with a duration of 20 s were applied: 1) transmastoidal GVS steps of 2 mA with the head in a pitched nose-down position and 2) angular head rotations around a combined roll-yaw axis parallel to the gravity vector with the head in the same position. The stimulation profile was individually scaled to match the nystagmus properties from GVS and consisted of a sustained velocity step of 4–12°/s on which a velocity ramp of 0.67–2°/s2was superimposed. Since blinks were reported to induce transient torsional eye movements, the subjects were also asked to blink once 10 s after stimulus onset. Analysis of torsional eye movements under both conditions revealed no significant differences. Thus we conclude that both the tonic and the phasic OT responses to GVS can be reproduced by pure rotational stimulations and that the OT-related effects of GVS on SCC afferents are similar to natural stimulations at small amplitudes.
Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIoNeurons by Presynaptic α2-Adrenergic Receptors
Authors: Pan Yu-Zhen , Li De-Pei , Pan Hui-Lin
Published: July 2016

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIoneurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIoneurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIoneurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIoneurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.
Responses of Spinothalamic Lamina I Neurons to Repeated Brief Contact Heat Stimulation in the Cat
Authors: Craig A. D. , Andrew D.
Published: July 2016

It was recently shown that repeated heat stimulation, using brief contacts (<1 s) with a preheated thermode at sufficiently short interstimulus intervals (ISIs <5 s) and high temperatures (≥51°C), will elicit in humans a sensation of rapidly augmenting “second” (burning) pain with only a weak “first” (sharp) pain sensation. Most strikingly, at short intertrial intervals (ITIs >5 s) such summation will reset, or begin again at baseline. In the present experiments, the responses of nociceptive lamina I spinothalamic (STT) neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were examined using this repeated brief contact heat paradigm. The neurons were classified as nociceptive-specific (NS, n = 8) or polymodal nociceptive (HPC, n = 8) based on their responses to quantitative thermal stimuli; all had receptive fields on the glabrous ventral hindpaw. A pneumatic piston was used to apply a thermode preheated to 34, 46, 49, 53, or 58°C with a contact dwell time of ∼0.7 s to the ventral hindpaw repeatedly (15 times) at ISIs of 2, 3, and 5 s, with 3–5 min between trials. The mean responses of the 16 nociceptive lamina I STT cells showed rapid temporal summation that was directly dependent on temperature and inversely dependent on ISI, with the greatest increases occurring between the 3rd and 10th contacts. The temporal profiles of this family of curves correspond with the psychophysical data on human sensation. Further analysis showed that this summation was due to the HPC cells, which all showed strong summation; in contrast, the NS cells showed little, if any. The HPC responses to the repeated heat stimuli lagged each contact by ∼1 s, consistent with the strong, monosynaptic C-fiber input that is characteristic of HPC cells and also with the dependence of second pain on C-fiber nociceptors. HPC cells also displayed the reset phenomenon at short ITIs, again in correspondence with the psychophysical data. The summation and the reset displayed by HPC cells were not related to skin temperature. Thus the results presented in this study, together with those in the preceding article, demonstrate a double dissociation indicating that NS and HPC lamina I STT cells can subserve the qualitatively distinct sensations of first (sharp) and second (burning) pain, respectively. These findings support the concept that the lamina I STT projection comprises several discrete sensory channels that are integrated in the forebrain to generate distinct sensations.
Threshold Conditions for Synaptically Evoking Ca2+Waves in Hippocampal Pyramidal Neurons
Authors: Zhou Suya , Ross William N.
Published: July 2016

Regenerative Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular stores in the form of Ca2+ waves leads to large-amplitude [Ca2+]iincreases in the apical dendrites of hippocampal CA1 pyramidal neurons. Release is generated following synaptic activation of group I metabotropic glutamate (mGlu) receptors. We systematically examined the conditions for evoking these waves in transverse slices from 2- to 3-wk-old rats. Using a sharpened asymmetrical bipolar tungsten stimulating electrode placed in the stratum radiatum, we varied the lateral position of the electrode, the number of stimulating pulses, the train frequency, and stimulus current. Several trends were clear. Increasing the frequency of stimulation from 20 to 100 Hz, keeping the total number of pulses constant, lowered the required stimulus current. Stimulation at frequencies below 20 Hz made it difficult to evoke release. Increasing the number of stimulation pulses, keeping the frequency constant, lowered the threshold current. A minimum of five pulses at 100 Hz was required to evoke release reliably, but several examples of success with three pulses were recorded. Theta-burst stimulation was as effective as tetanic stimulation. Placing the point of the stimulation electrode closer to the pyramidal neuron made it easier to evoke release, although stimulation at a lateral distance of 500 μm with unsharpened electrodes was sometimes successful. The simplest explanation for these results is that a bolus of IP3 must be produced quickly in a restricted region of the dendrites to generate Ca2+ waves. The conditions necessary for evoking regenerative Ca2+ release have many parallels (and some differences) with the conditions required to evoke long-term potentiation in these cells following tetanic stimulation.
Quantitative Analysis of Catch-Up Saccades During Sustained Pursuit
Authors: de Brouwer Sophie , Missal Marcus , Barnes Graham , Lefèvre Philippe
Published: July 2016

During visual tracking of a moving stimulus, primates orient their visual axis by combining two very different types of eye movements, smooth pursuit and saccades. The purpose of this paper was to investigate quantitatively the catch-up saccades occurring during sustained pursuit. We used a ramp-step-ramp paradigm to evoke catch-up saccades during sustained pursuit. In general, catch-up saccades followed the unexpected steps in position and velocity of the target. We observed catch-up saccades in the same direction as the smooth eye movement (forward saccades) as well as in the opposite direction (reverse saccades). We made a comparison of the main sequences of forward saccades, reverse saccades, and control saccades made to stationary targets. They were all three significantly different from each other and were fully compatible with the hypothesis that the smooth pursuit component is added to the saccadic component during catch-up saccades. A multiple linear regression analysis was performed on the saccadic component to find the parameters determining the amplitude of catch-up saccades. We found that both position error and retinal slip are taken into account in catch-up saccade programming to predict the future trajectory of the moving target. We also demonstrated that the saccadic system needs a minimum period of approximately 90 ms for taking into account changes in target trajectory. Finally, we reported a saturation (above 15°/s) in the contribution of retinal slip to the amplitude of catch-up saccades.
Adenosine Acting on A1 Receptors Protects NO-Triggered Rebound Potentiation and LTP in Rat Hippocampal Slices
Authors: Bon Christelle L. M. , Garthwaite John
Published: July 2016

Exposure of hippocampal slices to nitric oxide (NO) results in a depression of CA1 synaptic transmission. Under 0.2-Hz stimulation, washout of NO leads to a persistent potentiation that depends on N-methyl-d-aspartate (NMDA) receptors and endogenous NO formation and that occludes tetanus-induced long-term potentiation (LTP). The experiments were initially aimed at determining the relationship between the NO-induced synaptic depression and rebound potentiation. The adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) partially inhibited the depression produced by the NO donor diethylamine NONOate (300 μM). It also led to a complete block of both the rebound potentiation and the subsequent tetanus-induced LTP. LTP was preserved in the presence of DPCPX if the stimulation frequency was reduced to 0.033 Hz or if the NO application was omitted. The NO-triggered rebound potentiation was restored if the experiment (DPCPX followed by exogenous NO) was conducted in the presence of an NMDA antagonist. The restored potentiation was completely blocked by the NO synthase inhibitor,l-nitroarginine. It is concluded that the NO-induced depression is partially mediated by increased release of endogenous adenosine acting on A1 receptors. Moreover, tonic A1 receptor activation by adenosine protects LTP and the rebound potentiation from being disabled by untimely NMDA receptor activity. Hence, the NO-induced depression and rebound potentiation are linked in the sense that the depression helps to preserve the capacity of the synapses to undergo potentiation. Finally, the results give the first example of exogenous NO eliciting an enduring potentiation of hippocampal synaptic transmission that is dependent on endogenous NO formation, but not on NMDA receptors.
Representation of Spectral and Temporal Envelope of Twitter Vocalizations in Common Marmoset Primary Auditory Cortex
Authors: Nagarajan Srikantan S. , Cheung Steven W. , Bedenbaugh Purvis , Beitel Ralph E. , Schreiner Christoph E. , Merzenich Michael M.
Published: July 2016

Cortical sensitivity in representations of behaviorally relevant complex input signals was examined in recordings from primary auditory cortical neurons (AI) in adult, barbiturate-anesthetized common marmoset monkeys ( Callithrix jacchus). We studied the robustness of distributed responses to natural and degraded forms of twitter calls, social contact vocalizations comprising several quasi-periodic phrases of frequency and AM. We recorded neuronal responses to a monkey's own twitter call (MOC), degraded forms of their twitter call, and sinusoidal amplitude modulated (SAM) tones with modulation rates similar to those of twitter calls. In spectral envelope degradation, calls with narrowband channels of varying bandwidths had the same temporal envelope as a natural call. However, the carrier phase was randomized within each narrowband channel. In temporal envelope degradation, the temporal envelope within narrowband channels was filtered while the carrier frequencies and phases remained unchanged. In a third form of degradation, noise was added to the natural calls. Spatiotemporal discharge patterns in AI both within and across frequency bands encoded spectrotemporal acoustic features in the call although the encoded response is an abstract version of the call. The average temporal response pattern in AI, however, was significantly correlated with the average temporal envelope for each phrase of a call. Response entrainment to MOC was significantly correlated with entrainment to SAM stimuli at comparable modulation frequencies. Sensitivity of the response patterns to MOC was substantially greater for temporal envelope than for spectral envelope degradations. The distributed responses in AI were robust to additive continuous noise at signal-to-noise ratios ≥10 dB. Neurophysiological data reflecting response sensitivity in AI to these forms of degradation closely parallel human psychophysical results on the intelligibility of degraded speech in quiet and noisy conditions.
Dopamine Excites Fast-Spiking Interneurons in the Striatum
Authors: Bracci Enrico , Centonze Diego , Bernardi Giorgio , Calabresi Paolo
Published: July 2016

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).
Distribution of Eye- and Arm-Movement-Related Neuronal Activity in the SEF and in the SMA and Pre-SMA of Monkeys
Authors: Fujii Naotaka , Mushiake Hajime , Tanji Jun
Published: July 2016

We analyzed neuronal activity in the supplementary eye field (SEF), supplementary motor area (SMA), and presupplementary motor area (pre-SMA) during the performance of three motor tasks: capturing a visual target with a saccade, reaching one arm to a target while gazing at a visual fixation point, or capturing a target with a saccade and arm-reach together. Our data demonstrated that each area was involved in controlling the arm and eye movements in a different manner. Saccade-related neurons were found mainly in the SEF. In contrast, arm-movement-related neurons were found primarily in the SMA and pre-SMA. In addition, we found that the activity of both arm-movement- and saccade-related neurons differed depending on the presence or absence of an accompanying saccade or arm movement. Such context dependency was found in all three areas. We also discovered that activity preceding eye or arm movement alone, and eye and arm movement combined, appeared more often in the pre-SMA and SEF, suggesting their involvement in effector-independent aspects of motor behavior. Subsequent analysis revealed that the laterality of arm representation differed in the three areas: it was predominantly contralateral in the SMA but largely bilateral in the pre-SMA and SEF.
Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus control cardiovascular reactivity and anxiety-like behavior in male mice
Authors: Wang Lei , Hiller Helmut , Smith Justin A. , de Kloet Annette D. , Krause Eric G.
Published: July 2016

This study tested the hypothesis that deletion of angiotensin type 1a receptors (AT1a) from the paraventricular nucleus of hypothalamus (PVN) attenuates anxiety-like behavior, hypothalamic-pituitary-adrenal (HPA) axis activity, and cardiovascular reactivity. We used the Cre/LoxP system to generate male mice with AT1aspecifically deleted from the PVN. Deletion of the AT1afrom the PVN reduced anxiety-like behavior as indicated by increased time spent in the open arms of the elevated plus maze. In contrast, PVN AT1adeletion had no effect on HPA axis activation subsequent to an acute restraint challenge but did reduce hypothalamic mRNA expression for corticotropin-releasing hormone (CRH). To determine whether PVN AT1adeletion inhibits cardiovascular reactivity, we measured systolic blood pressure, heart rate, and heart rate variability (HRV) using telemetry and found that PVN AT1adeletion attenuated restraint-induced elevations in systolic blood pressure and elicited changes in HRV indicative of reduced sympathetic nervous activity. Consistent with the decreased HRV, PVN AT1adeletion also decreased adrenal weight, suggestive of decreased adrenal sympathetic outflow. Interestingly, the altered stress responsivity of mice with AT1adeleted from the PVN was associated with decreased hypothalamic microglia and proinflammatory cytokine expression. Collectively, these results suggest that deletion of AT1afrom the PVN attenuates anxiety, CRH gene transcription, and cardiovascular reactivity and reduced brain inflammation may contribute to these effects.
Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment
Authors: Chen Xinfeng , Song Mengjia , Zhang Bin , Zhang Yi
Published: July 2016

Reactive oxygen species (ROS) produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor‐induced immunosuppression. T cell‐based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell‐based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity.
Air Pollution Monitoring and Control System for Subway Stations Using Environmental Sensors
Authors: Kim Gyu-Sik , Son Youn-Suk , Lee Jai-Hyo , Kim In-Won , Kim Jo-Chun , Oh Joon-Tae , Kim Hiesik
Published: July 2016

The metropolitan city of Seoul uses more energy than any other area in South Korea due to its high population density. It also has high emissions of air pollutants. Since an individual usually spends most of his/her working hours indoors, the ambient air quality refers to indoor air quality. In particular, PM10concentration in the underground areas should be monitored to preserve the health of commuters in the subway system. Seoul Metro and Seoul Metropolitan Rapid Transit Corporation measure several air pollutants regularly. In this study, the accuracy of an instrument for PM measurement using the light scattering method was improved with the help of a linear regression analysis technique to continuously measure thePM10concentrations in subway stations. In addition, an air quality monitoring system based on environmental sensors was implemented to display and record the data of PM10, CO2, temperature, and humidity. Through experimental studies, we found that ventilation fans could improve air quality and decrease PM10concentrations in the tunnels effectively by increasing the air flow rate.
Nonfragile Robust Model Predictive Control for Uncertain Constrained Systems with Time-Delay Compensation
Authors: Jiang Wei , Wang Hong-li , Lu Jing-hui , Qin Wei-wei , Cai Guang-bin
Published: July 2016

This study investigates the problem of asymptotic stabilization for a class of discrete-time linear uncertain time-delayed systems with input constraints. Parametric uncertainty is assumed to be structured, and delay is assumed to be known. In Lyapunov stability theory framework, two synthesis schemes of designing nonfragile robust model predictive control (RMPC) with time-delay compensation are put forward, where the additive and the multiplicative gain perturbations are, respectively, considered. First, by designing appropriate Lyapunov-Krasovskii (L-K) functions, the robust performance index is defined as optimization problems that minimize upper bounds of infinite horizon cost function. Then, to guarantee closed-loop stability, the sufficient conditions for the existence of desired nonfragile RMPC are obtained in terms of linear matrix inequalities (LMIs). Finally, two numerical examples are provided to illustrate the effectiveness of the proposed approaches.
In Situ Test of Grouting Reinforcement for Water-Enriched Sandy Gravel Ground in River Floodplain
Authors: Lai Jinxing , Feng Zhihua , Qiu Junling , Chen Jianxun , Fan Haobo
Published: July 2016

The performance of the ground treatment is always critical for a tunnel excavated in unstable stratum. Laodongnanlu Xiangjiang Tunnel (Changsha, China) across the Xiangjiang River will be constructed in a sandy gravel ground which is characterized by loose structure, extensive porosity, elevated sensitivity, poor stability, and a high groundwater table. Permeation grouting will be employed to improve the bearing capacity and mitigate groundwater movement into the excavation. In order to seek suitable injection parameters and grouting method, a field trial of vertical grouting was conducted in the sandy gravel stratum in river floodplain. A series of tests focusing on grout material, grouting sequence of boreholes, injection pressure, and grouting volume were performed to improve the sandy gravel mass strength and reduce water permeability. The examination of the results obtained during water pressure testing and core drilling on completion of the grouting trial successfully demonstrated that the specified injection criteria had led to an expected effect. Grouting control method of this saturated sandy gravel stratum was concluded after the test, which would contribute to the future pregrouting work during the tunnelling.
Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks
Authors: Xu Jingyu , Wang Panpan , Yang Hong , Zhou Jin , Li Yinghong , Li Xiaoxu , Xue Weiwei , Yu Chunyan , Tian Yubin , Zhu Feng
Published: July 2016

Kinase is one of the most productive classes of established targets, but the majority of approved drugs against kinase were developed only for cancer. Intensive efforts were therefore exerted for releasing its therapeutic potential by discovering new therapeutic area. Kinases in clinical trial could provide great opportunities for treating various diseases. However, no systematic comparison between system profiles of established targets and those of clinical trial ones was conducted. The reveal of probable difference or shift of trend would help to identify key factors defining druggability of established targets. In this study, a comparative analysis of system profiles of both types of targets was conducted. Consequently, the systems profiles of the majority of clinical trial kinases were identified to be very similar to those of established ones, but percentages of established targets obeying the system profiles appeared to be slightly but consistently higher than those of clinical trial targets. Moreover, a shift of trend in the system profiles from the clinical trial to the established targets was identified, and popular kinase targets were discovered. In sum, this comparative study may help to facilitate the identification of the druggability of established drug targets by their system profiles and drug-target interaction networks.
Therapies for Prevention and Treatment of Alzheimer’s Disease
Authors: Mendiola-Precoma J. , Berumen L. C. , Padilla K. , Garcia-Alcocer G.
Published: July 2016

Alzheimer’s disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-βpeptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.
Automated Determination of Arterial Input Function for Dynamic Susceptibility Contrast MRI from Regions around Arteries Using Independent Component Analysis
Authors: Chen Sharon , Tyan Yu-Chang , Lai Jui-Jen , Chang Chin-Ching
Published: July 2016

Purpose.Quantitative cerebral blood flow (CBF) measurement using dynamic susceptibility contrast- (DSC-) MRI requires accurate estimation of the arterial input function (AIF). The present work utilized the independent component analysis (ICA) method to determine the AIF in the regions adjacent to the middle cerebral artery (MCA) by the alleviated confounding of partial volume effect.Materials and Methods.A series of spin-echo EPI MR scans were performed in 10 normal subjects. All subjects received 0.2 mmol/kg Gd-DTPA contrast agent. AIFs were calculated by two methods:(1)the region of interest (ROI) selected manually and(2)weighted average of each component selected by ICA (weighted-ICA). The singular value decomposition (SVD) method was then employed to deconvolve the AIF from the tissue concentration time curve to obtain quantitative CBF values.Results. The CBF values calculated by the weighted-ICA method were 41.1 ± 4.9 and 22.1 ± 2.3 mL/100 g/min for cortical gray matter (GM) and deep white matter (WM) regions, respectively. The CBF values obtained based on the manual ROIs were 53.6 ± 12.0 and 27.9 ± 5.9 mL/100 g/min for the same two regions, respectively.Conclusion.The weighted-ICA method allowed semiautomatic and straightforward extraction of the ROI adjacent to MCA. Through eliminating the partial volume effect to minimum, the CBF thus determined may reflect more accurate physical characteristics of theT2⁎signal changes induced by the contrast agent.
Discrete Event Simulation Models for CT Examination Queuing in West China Hospital
Authors: Luo Li , Liu Hangjiang , Liao Huchang , Tang Shijun , Shi Yingkang , Guo Huili
Published: July 2016

In CT examination, the emergency patients (EPs) have highest priorities in the queuing system and thus the general patients (GPs) have to wait for a long time. This leads to a low degree of satisfaction of the whole patients. The aim of this study is to improve the patients’ satisfaction by designing new queuing strategies for CT examination. We divide the EPs into urgent type and emergency type and then design two queuing strategies: one is that the urgent patients (UPs) wedge into the GPs’ queue with fixed interval (fixed priority model) and the other is that the patients have dynamic priorities for queuing (dynamic priority model). Based on the data from Radiology Information Database (RID) of West China Hospital (WCH), we develop some discrete event simulation models for CT examination according to the designed strategies. We compare the performance of different strategies on the basis of the simulation results. The strategy that patients have dynamic priorities for queuing makes the waiting time of GPs decrease by 13 minutes and the degree of satisfaction increase by 40.6%. We design a more reasonable CT examination queuing strategy to decrease patients’ waiting time and increase their satisfaction degrees.
Analysis of the Oceanic Wave Dynamics for Generation of Electrical Energy Using a Linear Generator
Authors: Farrok Omar , Islam Md. Rabiul , Sheikh Md. Rafiqul Islam
Published: July 2016

Electricity generation from oceanic wave depends on the wave dynamics and the behavior of the ocean. In this paper, a permanent magnet linear generator (PMLG) has been designed and analyzed for oceanic wave energy conversion. The proposed PMLG design is suitable for the point absorber type wave energy device. A mathematical model of ocean wave is presented to observe the output characteristics and performance of the PMLG with the variation of ocean waves. The generated voltage, current, power, applied force, magnetic flux linkage, and force components of the proposed PMLG have been presented for different sea wave conditions. The commercially available software package ANSYS/ANSOFT has been used to simulate the proposed PMLG by the finite element method. The magnetic flux lines, flux density, and field intensity of the proposed PMLG that greatly varies with time are presented for transient analysis. The simulation result shows the excellent features of the PMLG for constant and variable speeds related to wave conditions. These analyses help to select proper PMLG parameters for better utilization of sea wave to maximize output power.