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Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O2, 93% N2) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specificTrpa1knockout (asTrpa1−/−) and floxedTrpa1(Trpa1f/f) mice. In bothTrpa1f/fand asTrpa1−/−mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.

It is supposed that the nucleus of the solitary tract (NTS) in the dorsal medulla includes gas sensor cells responsive to hypercapnia or hypoxia in the central nervous system. In the present study, we analyzed cellular responses to hypercapnia and hypoxia in the NTS region of newborn rat in vitro preparation. The brainstem and spinal cord were isolated from newborn rat (P0-P4) and were transversely cut at the level of the rostral area postrema. To detect cellular responses, calcium indicator Oregon Green was pressure-injected into the NTS just beneath the cut surface of either the caudal or rostral block of the medulla, and the preparation was superfused with artificial cerebrospinal fluid (25–26°C). We examined cellular responses initially to hypercapnic stimulation (to 8% CO2 from 2% CO2) and then to hypoxic stimulation (to 0% O2 from 95% O2 at 5% CO2). We tested these responses in standard solution and in two different synapse blockade solutions: (1) cocktail blockers solution including bicuculline, strychnine, NBQX and MK-801 or (2) TTX solution. At the end of the experiments, the superfusate potassium concentration was lowered to 0.2 from 3 mM to classify recorded cells into neurons and astrocytes. Excitation of cells was detected as changes of fluorescence intensity with a confocal calcium imaging system. In the synaptic blockade solutions (cocktail or TTX solution), 7.6 and 8% of the NTS cells responded to hypercapnic and hypoxic stimulation, respectively, and approximately 2% of them responded to both stimulations. Some of these cells responded to low K+, and they were classified into astrocytes comprising 43% hypercapnia-sensitive cells, 56% hypoxia-sensitive cells and 54% of both stimulation-sensitive cells. Of note, 49% of the putative astrocytes identified by low K+ stimulation were sensitive to hypercapnia, hypoxia or both. In the presence of a glia preferential blocker, 5 mM fluoroacetate (plus 0.5 μM TTX), the percentage of hypoxia-sensitive cells was significantly reduced compared to those of all other conditions. This is the first study to reveal that the NTS includes hypercapnia and hypoxia dual-sensitive cells. These results suggest that astrocytes in the NTS region could act as a central gas sensor.

Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifier of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.

Background and objective Body weight of patients with obstructive sleep apnea after initiation of nasal continuous positive airway pressure appears to increase. We hypothesized that intermittent hypoxia (IH) will decrease energy expenditure (EE), and that normoxic recovery will lead to body weight gains. Methods C57BL/6 J male mice were exposed to either 12 h/day of mild IH (alternating FIO2-10-11% and 21%; 640 s cycle), or severe IH (FIO2-6-7%-21%; 180 s cycle) or sham IH daily for 4 or 8 weeks. After exposures, EE was evaluated while mice were kept under normoxia for 5 weeks and organ histology was evaluated. Results EE was not decreased by IH. However, visceral white adipocyte size after normoxic recovery was significantly increased in severe IH in an intensity-dependent manner. Conclusion Our hypothesis that IH would decrease EE was not corroborated. However, IH and normoxic recovery seem to promote severity-dependent enlargement of visceral adipocytes, likely reflecting altered energy preservation mechanisms induced by IH.

Objectives: Recent reports on venous blood gas analysis have shown that venous bicarbonate concentration is useful in the evaluation of the body acid-base status. Most of these reports have been based on the Bland-Altman analysis comparing arterial and venous blood gas values. We intended to elucidate any factors that decrease the agreement between venous and arterial bicarbonate concentrations, which might impair the usefulness of venous blood gas analysis. Methods: Healthy volunteers and patients with various diseases (n = 141) were evaluated by simultaneous arterial and venous blood sampling and Bland-Altman analysis. The venous-arterial bicarbonate concentration difference was compared between healthy volunteers and untreated respiratory alkalosis patients. Intentional hyperventilation (30 or 60 breaths/min, for 3 min) was also performed on 6 healthy volunteers and the venous-arterial bicarbonate concentration difference was evaluated. Results: The relative average bias in bicarbonate concentration was 2.00 mEq/l with venous bicarbonate higher than arterial bicarbonate with 95% limits of agreement of ±4.15 mEq/l. Hyperventilation challenges increased the venous-arterial bicarbonate concentration difference in an intensity-dependent manner. The venous-arterial bicarbonate concentration difference was higher in untreated respiratory alkalosis patients than in healthy volunteers (P Conclusion: Although venous bicarbonate may be useful to evaluate the body acid-base status, hyperventilation increases the venous-arterial bicarbonate concentration difference. Physicians should keep this phenomenon in mind.

Objective: The Japanese drug use system allowed the “once-daily use” of inhaled corticosteroid (ICS) fluticasone furoate (FF) combined with a long acting beta-2 agonist (LABA) vilanterol (VI) against asthma for the first time in 2013. Until then, patients with asthma had to use ICS at least twice-daily. We investigated the real-world efficacy and problems of this drug (FF/VI). Methods: This was an open-label, uncontrolled, within-group time-series (before-after) design. Prior treatments of asthma (twice-daily use of ICS with or without LABA) were switched to once-daily use of FF/VI (200 μg/25 μg). Subjects were evaluated by lung function tests prior to, and 2–3 months after, the initiation of FF/VI. Questions on the asthma control test (ACT) and preference of drugs were asked to patients. Results: One hundred and twenty-eight Japanese asthma outpatients were enrolled from 2014–2018 and 107 subjects completed the study. Peak flow, instantaneous flow at 75% of the forced vital capacity (V75), V50, maximum mid-expiratory flow rate, forced expiratory volume in 1 s, and ACT score in FF/VI-using subjects were significantly increased (all p

Dimethyl sulfoxide (DMSO) is commonly used as a solvent for hydrophobic substances, but the compound’s innate bioactivity is an area of limited understanding. In this investigation we seek to determine the analgesic potential of DMSO. We addressed the issue by assessing the perception of thermal pain stimulus, using a 55 °C hotplate design, in conscious mice. The latency of withdrawal behaviors over a range of incremental accumulative intraperitoneal DMSO doses (0.5–15.5 g/kg) in the same mouse was taken as a measure of thermal endurance. The findings were that the latency, on average, amounted to 15–30 s and it differed inappreciably between the sequential DMSO conditions. Nor was it different from the pre-DMSO control conditions. Thus, DMSO did not influence the cutaneous thermal pain perception. The findings do not lend support to those literature reports that point to the plausible antinociceptive potential of DMSO as one of a plethora of its innate bioactivities. However, the findings concern the mouse’s footpad nociceptors which have specific morphology and stimulus transduction pathways, which cannot exclude DMSO’s antinociceptive influence on other types of pain or in other types of skin. Complex and as yet unresolved neural mechanisms of perception of cutaneous noxious heat stimulus should be further explored with alternative experimental designs.

This review tackles the unresolved issue of the existence of oxygen sensor in the body. The sensor that would respond to changes in tissue oxygen content, possibly along the hypoxia-normoxia-hyperoxia spectrum, rather than to a given level of oxygen, and would translate the response into lung ventilation changes, the major adaptive process. Studies on oxygen sensing, for decades, concentrated around the hypoxic ventilatory response generated mostly by carotid body chemoreceptor cells. Despite gaining a substantial insight into the cellular transduction pathways in carotid chemoreceptors, the exact molecular mechanisms of the chemoreflex have never been conclusively verified. The article briefly sums up the older studies and presents novel theories on oxygen, notably, hypoxia sensing. These theories have to do with the role of transient receptor potential cation TRPA1 channels and brain astrocytes in hypoxia sensing. Although both play a substantial role in shaping the ventilatory response to hypoxia, neither can yet be considered the ultimate sensor of hypoxia. The enigma of oxygen sensing in tissue still remains to be resolved.

otC), is the kernel for respiratory rhythm generation. Despite previous extensive studies focusing on neurons,themechanismofhowrespiratoryrhythmisgeneratedhasnotbeenfullyunderstood. • Here we show that non-neuronal glial cells (a subset of putative astrocytes) in the preB¨ are periodically activated preceding inspiratory neuronal activity, periodic activity of putative astrocytes persists during blockade of neuronal activity, and stimulation of astrocytes in the preB¨ otC induces inspiratory neuronal firings. • These findings together with the previous report that blockade of astrocytic metabolism abolishes inspiratory neural output suggest that astrocytes are functionally involved in respiratory rhythm generation. • These results will help us better understand how respiratory rhythm is generated and how respiratory output is disturbed in various pathological conditions.

Ventilatory responses to opioids are complex and not yet fully understood. We evaluated concentration-dependent effects of a selective μ-opioid receptor agonist [ d -Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) on respiratory output in the arterially perfused in situ rat preparation, which preserves the integrity of the ponto-medullary respiratory network. DAMGO (300–3400 nM) was added accumulatively to the perfusate. DAMGO increased inspiratory time and diminished central vagal post-inspiratory activity. At 300–500 nM DAMGO caused rapid breathing with shortening of expiratory time. The change of breathing pattern occurred within a single breath. Bilateral vagotomy did not affect the change in respiratory pattern, suggesting that it was of central origin. Additional DAMGO up to 1800 nM did not affect the rapid breathing pattern, and further elevated concentrations (up to 3400 nM) caused inconsistent results. Since the rapid breathing pattern was associated with the obliteration of vagal post-inspiratory activity, we conclude that DAMGO reconfigures the respiratory output to an inspiratory phase-dominant, rapidly alternating inspiration–expiration pattern.

Two putative respiratory rhythm generators (RRGs), the para-facial respiratory group (pFRG) and the pre-Botzinger complex (preBotC), have been identified in the neonatal rodent brainstem. To elucidate their functional roles during the neonatal period, we evaluated developmental changes of these RRGs by optical imaging using a voltage-sensitive dye. Optical signals, recorded from the ventral medulla of brainstem-spinal cord preparations of neonatal (P0-P4) rats (n = 44), were analysed by a cross correlation method. With development during the first few postnatal days, the respiratory-related activity in the pFRG reduced and shifted from a preinspiratory (P0-P1) to an inspiratory (P2-P4) pattern, whereas preBotC activity remained unchanged. The mu-opioid agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) augmented preinspiratory activity in the pFRG, while the mu-opioid antagonist naloxone induced changes in spatiotemporal activation profiles that closely mimicked the developmental changes. These results are consistent with the recently proposed hypothesis by Janczewski and Feldman that the pFRG is activated to compensate for the depression of the preBotC by perinatal opiate surge. We conclude that significant reorganization of the respiratory neuronal network, characterized by a reduction of preinspiratory activity in the pFRG, occurs at P1-P2 in rats. The changes in spatiotemporal activation profiles of the pFRG neurones may reflect changes in the mode of coupling of the two respiratory rhythm generators.

Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents for hydrophobic substances in biological experiments. In addition, the compound exhibits a plethora of bioactivities, which makes it of potential pharmacological use of its own. The influence on respiration, and thus on arterial blood oxygenation, of DMSO is unclear, contentious, and an area of limited study. Thus, in the present investigation we set out to determine the influence on lung ventilation of cumulated doses of DMSO in the amount of 0.5, 1.5, 3.5, 7.5, and 15.5 g/kg; each dose given intraperitoneally at 1 h interval in conscious mice. Ventilation and its responses to 7 % hypoxia (N(2) balanced) were recorded in a whole body plethsymograph. We demonstrate a dose-dependent inhibitory effect of DMSO on lung ventilation and its hypoxic responsiveness, driven mostly by changes in the tidal component. The maximum safe dose of DMSO devoid of meaningful consequences for respiratory function was 3.5 g/kg. The dose of 7.5 g/kg of DMSO significantly dampened respiration, with yet well preserved hyperventilatory response to hypoxia. The highest dose of 15.5 g/kg severely impaired ventilation and its responses. The study delineates the safety profile of DMSO regarding the respiratory function which is essential for maintaining proper tissue oxygenation. Caution should be exercised concerning dose concentration of DMSO.

To examine the role of GABA in the respiratory rhythm and pattern generation in neonatal mice, we analyzed the function of the respiratory control system of 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient neonatal mice. In these mutant (GAD67-/-) mice, GABA levels in the brainstem were reduced to about 30% of those in wild-type (GAD67+/+) mice. In in vivo preparations, ventilatory parameters were analyzed by whole body plethysmography and electromyography of intercostal muscles. GAD67-/- mice exhibited abnormal respiratory patterns, i.e. irregular respiratory rhythm, and periodic gasp-like respiration followed by shallow breathing with short inspiratory duration and apnea. In in vitro GAD67-/- brainstem-spinal cord preparations, inspiratory C4 burst duration was shorter than that in GAD67+/+ preparations. Whole cell recordings revealed that activities of inspiratory neurons in the ventral medulla of GAD67-/- mice were characterized by a short depolarization period and a paucity of firing during the inspiratory phase. Superfusion of the in vitro GAD67-/- preparation with 10 microM GABA prolonged C4 burst duration and partly restored a normal pattern of inspiration, although the restoration was limited. These results indicate that reduced GABA levels during the perinatal period induce malfunction in the respiratory control system. We suggest that GABAergic transmission is not essential for basic respiratory rhythm generation but plays an important role in the maintenance of regular respiratory rhythm and normal inspiratory pattern in neonatal mice.

We have measured the precise lattice parameter of undoped and impurity-doped ZnSe single crystals by the Fewster method. The lattice parameter of undoped ZnSe single crystals was 0.566919±0.000002 nm and it remained unchanged after the Zn-treatment at 1000°C. On the other hand, dilation of lattice parameter observed in I-doped ZnSe depended on Zn-treatment temperature. Increase of lattice parameter also occurred in Al-doped ZnSe. These results suggest that I and Al impurities in ZnSe crystal play an important role with point defects formation during and after the Zn heat treatment.

Lattice parameters of annealed ZnSe crystals have been measured by the Bond method. The annealing was carried out at 1000°C under a definite Zn partial pressure maintained by heating a Zn reservoir after growth from the melt under Zn partial pressure. The lattice parameter, a , depends on the Zn reservoir temperature during annealing, T Zn (A); a =0.566898±0.000005 nm at T Zn (A) of 450–600°C, a =0.566910±0.000005 nm at T Zn (A) of 750°C and a =0.566913±0.000003 nm at T Zn (A) of 900°C. The dependence of lattice parameter on Zn partial pressure is discussed.

Dependence of the lattice parameter of melt-grown ZnSe on Zn partial pressure have been measured by the Bond method. The lattice parameters changed between 0.566902 and 0.566908 nm depending on the partial pressure of Zn during growth. The minimum lattice parameter was observed at the Zn reservoir temperature of 1000°C, where the melt composition was near stoichiometry.

Objectives: A meta-analysis suggested that the use of varenicline, which is a partial agonist of nicotinic acetylcholine receptors and is effective in smoking cessation, increases the risk of cardiovascular events within 52 weeks of starting treatment. Defining these events as occurring during drug treatment (usually for 12 weeks) or within 30 days of discontinuation, another meta-analysis showed that the risk was statistically insignificant. In the present study, we aimed to clarify the effect of varenicline-assisted smoking cessation on vascular endothelial function assessed by flow-mediated vasodilation (FMD). Design: Before–after and time-series. Setting: Tochigi Prefecture, Japan. Participants: Data of 85 participants who visited nicotine-dependent outpatient services were reviewed. FMD was repeatedly measured in 33 of the 85 participants. Inclusion criteria: 20 years and older, Brinkman index ≥200, Tobacco Dependence Screener ≥5 and stated motivation to quit smoking. Interventions: Each participant was treated with varenicline titrated up to 1.0 mg twice daily (for 12 weeks in total). Primary and secondary outcome measures: Participants were evaluated by FMD prior to, and 3 months after, complete smoking cessation. Follow-up FMD measurements were carried out every 3 months if possible. Changes in FMD during varenicline use were also evaluated. Results: FMD was significantly increased from 4.0±1.8% to 5.5±2.2% (p

The refractive indices and lattice constants of large KTP single crystals grown from a flux of K 6 P 4 O 13 have been investigated. Changes in their refractive index and lattice constant along the growth direction result from compositional deviation of the solution. Strong correlation is implied in the similar behavior of both the lattice constant and the refractive index. The lattice constant dependence on the compositional deviation seems to be due to variations in the solid solution range among the KTP components.

This article reports the notable effect of N doping in ZnSe on the band-gap energy. The free exciton energy in the epilayers with different N A − N D was measured by means of reflectance and photoreflectance spectroscopies. The temperature dependence of reflectance, photoreflectance and photoluminescence spectra of ZnSe:N epilayers was investigated in detail. It is found that the free exciton energy shifts to low energy side with increasing N concentration, indicating the shrinkage of the band-gap energy due to N doping. The peak positions of near-band-edge emissions shift to low energy side due to the shrinkage of energy gap. The lattice constant and the strain in N-doped ZnSe were measured by means of X-ray diffraction (XRD). The origins for the shrinkage of energy gap are discussed on the basis of the optical and XRD results.

Silicon is an amphoteric impurity of gallium arsenide that is present in different defect configurations. This work reports on the effects of heat treatment on defect reactions of heavily silicon‐doped gallium arsenide crystals. The distribution of segregation, lattice parameter, and electrical properties was studied for several heat treatments. When the crystals were bulk‐annealed at between 700 °C and 1000 °C for 20 h, zone‐distributed segregation was observed at the area with a silicon concentration of about 1×1019 cm−3 by etching and x‐ray topography. Regions observed to have silicon‐related segregation exhibited a decrease in lattice parameter when the crystals were annealed below 850 °C for 20 h then quenched. In addition, such regions exhibited little change in lattice parameter when the crystals were annealed above 850 °C. For electrical properties, the largest decrease in carrier concentration and mobility of such regions was observed when the crystals were annealed at 700 °C. This change in the ...

We investigated the effect of Si doping on the lattice parameter of gallium arsenide single crystals grown by the gradient freeze method. We also studied the carrier concentration and photoluminescence spectra of these crystals. We concluded that the lattice parameters of these crystals depend not only on the silicon concentration, but also on heat treatment and on melt composition. These changes in lattice parameter are assumed to relate to native defects and silicon clusters.

The synaptic organization between vesicular glutamate transporter 2 (VGLUT2)-immunoreactive (ir) axon terminals and phrenic motoneurons in the neonatal rat was examined using a combined retrograde tracing and immunohistochemistry for VGLUT2. The phrenic nucleus (PhN) contained large numbers of VGLUT2-ir axon terminals, some of which made axosomatic and axodendritic synapses with PhN motoneurons. These terminals were of asymmetrical type and contained spherical clear synaptic vesicles. The results suggest that in the neonatal rat glutamatergic synapses onto PhN motoneurons exist and mediate excitatory transmission to drive PhN motoneurons.

Breathing in mammals is controlled by neural networks in the brainstem such as the pre-Botzinger complex (preBotC) and the parafacial respiratory group (pFRG). Exploring these rhythmogenic networks and their interactions is greatly facilitated by live fluorescence imaging that enables analysis of (i) spatiotemporal patterns of respiratory (population) activities, (ii) (sub)cellular signaling in identified respiratory neurons, and (iii) membrane properties of respiratory neurons that are fluorescence-tagged for characteristic markers. Transversal medullary slices containing the preBotC and "en bloc" brainstem-spinal cord preparations with a functional preBotC/pFRG dual respiratory center which interacts, e.g., with pontine structures, are used for respiratory imaging in perinatal rodents. Imaging of less reduced (mature) respiratory networks is feasible in arterially-perfused "working-heart-brainstem" preparations from rodents. In these in situ models, imaging with voltage and Ca2+ sensitive dyes is established for assessment of respiratory (population) activities. Here, we summarize findings from diverse live imaging approaches in these models and point out potential pitfalls and future perspectives of respiratory-related optical recording.

The effect of wafer annealing on lattice parameter of liquid‐encapsulated Czochralski (LEC) grown undoped semi‐insulating GaAs crystals is investigated, showing that wafer annealing increases the lattice parameter from an anomalous state below that predicted by Vegard’s law. The sheet‐carrier concentration of a silicon‐implanted layer formed on undoped semi‐insulating GaAs increases with the increase in lattice parameter caused by the wafer annealing. The reduction of BGaVAs complex defects is a reasonable explanation for the increase in lattice parameter and sheet‐carrier concentration. In LEC‐grown silicon‐doped GaAs crystals, no anomalous reduction of lattice parameter is observed in as‐grown crystals. It is speculated that the silicon introduced into the crystal from the melt fills the VAs vacancies in the GaAs crystal before BGaVAs forms. BGaVAs complex defects in undoped GaAs crystal must be formed during the post‐growth cooling process.

Ventilation is closely tied to PaCO2 and PaO2 via a feedback control mechanism. Most importantly, changes in PCO2 and/or H+ (pH) are sensed by the central nervous system (CNS) resulting in directly related changes in ventilation. The magnitude of this response relative to the stimulus is known as, “central ventilatory chemosensitivity.” Several electrophysiological studies have demonstrated that chemosensitive neurons – i.e. neurons that change their electrical activity in response to a shift of PCO2/pH – are widely distributed throughout the brainstem (Bernard and Nattie, 1996; Coates and Nattie, 1993; Dean et al., 1989, 1990; Kawai et al., 1996; Oyamada et al., 1998, 1999; Richerson, 1995), suggesting that they could be the central CO2/pH sensors that regulate ventilation. In addition, PaO2 levels are inversely related to ventilation. The type I cells of the carotid body serve as the main sensors stimulating ventilation when PaO2 declines (“peripheral ventilatory chemosensitivity”). The afferent inputs from these PCO2/pHor PO2-sensitive cells converge at the respiratory center located in the brainstem, where the generation of respiratory neural activity is integrated. Potassium channels control the excitability of cells by setting its membrane potential. The importance of potassium channels in peripheral arterial chemoreception was first demonstrated by Lopez-Barneo et al. (1988). They showed, in the rabbit, that the potassium current was reduced by hypoxia in type I carotid body cells. More recently it has been observed, in the rat, that members of the tandem pore domain family, TASK-1 and TASK-3, are also inhibited by hypoxia in type I cells (Buckler et al., 2000) and H146 cells (Hartness et al., 2001). It has also been suggested that the Kv4 is the main subfamily involved in the O2-sensitive potassium current in type I cells in the rabbit (Perez-Garcia et al., 2000). Some potassium channels are also sensitive to CO2/pH (Buckler et al., 2000; Chapman et al., 2000; Kim et al., 2000; Lesage and Lazdunski, 2000; Rajan et al., 2000; Xu et al., 2000a; Zhu et al., 2000). This suggests that they may play a

Neuromuscular blocking agents suppress central respiratory activity through their inhibitory effects on preinspiratory neurons and the synaptic drive from preinspiratory neurons to inspiratory neurons. Central CO 2 -chemosensitive areas, which partly consist of CO 2 -excited neurons, in the rostral ventrolateral medulla are thought to provide tonic drive to the central respiratory network and involve cholinergic mechanisms, which led us to hypothesize that neuromuscular blocking agents can inhibit CO 2 -excited neurons and attenuate respiratory CO 2 responsiveness. To test this hypothesis, we used isolated brainstem-spinal cord preparations from newborn rats. The increase of C4 burst frequency induced by a hypercapnic superfusate, i.e. respiratory CO 2 responsiveness, was suppressed by the application of neuromuscular blocking agents, either d-tubocurarine (10, 100∝M) or vecuronium (100∝M). These agents (40∝M) also induced hyperpolarization and decreases in firing frequency of CO 2 -excited neurons in the rostral ventrolateral medulla. Our results demonstrate that neuromuscular blocking agents inhibit CO 2 -excited tonic firing neurons and attenuate respiratory CO 2 responsiveness. Key terms: brainstem, chemosensitivity, CO 2 responsiveness, muscle relaxant, nicotinic acetylcholine receptor

The significance of extracellular potassium in central respiratory control was investigated using the isolated brainstem–spinal cord preparation of the neonatal rat. Depth profiles of extracellular potassium activity ([K+])ECF in the medulla were measured with ion-sensitive microelectrodes. Although [K+]ECF increased with depth in medullary tissue during control (4 mM) and low (1 mM) potassium concentration ([K+])CSF superfusion, this gradient disappeared with higher [K+]CSF. With low [K+]CSF (1 mM), respiratory CO2 responsiveness was abolished, and increased with high [K+]CSF (8 mM). Respiratory frequency (fR) was diminished at low [K+]CSF (1 mM), and increased with elevated [K+]CSF (8 and 16 mM); with yet higher [K+]CSF (32 mM) apnea occurred after a transient increase in fR. Perforated patch recording revealed that high [K+]ECF decreased membrane resistance, depolarized membrane potential, and increased firing frequency in most of the recorded medullary neurons. High [K+]ECF also increased excitatory and inhibitory post-synaptic potentials of medullary neurons and augmented the functional connectivity among neurons. It is concluded that [K+]ECF is of importance in the maintenance of respiratory rhythm and central chemosensitivity.

We have developed a fast and stable measuring system of lattice spacing with precision of 10−8 for a silicon crystal at the Photon Factory. Using a combination of this system with an autocollimator, we can not only measure d‐spacing, but also can determine lattice plane orientation with sub‐arcsec resolution in the same measurement process. We report a mapping measurement of a Boron‐doped CZ silicon wafer with 1mm2 spatial resolution.

The molecular beam epitaxial growth processes of Al single‐crystal layers deposited at room temperature on As‐stabilized and on Al‐stabilized AlAs surfaces are investigated in situ using reflection high‐energy electron diffraction (RHEED). The epitaxy relationship of Al with the underlying AlAs is (011)[100]Al//(001)[110]AlAs irrespective of the surface stoichiometry of AlAs. Detailed RHEED investigation suggests that the initially deposited two one‐monolayer‐thick Al layers form a sphalerite lattice on As‐(Al‐)stabilized AlAs with the same lattice spacing as AlAs, while the deposition of additional Al layers induces the structural phase transition from the sphalerite lattice to an fcc lattice with bulk Al lattice constant. Thick epitaxial Al layers show (4×1) surface reconstruction.

The concentration of dominant native defects in a float-zoned Si single crystal at high temperatures was directly determined from the difference between the macroscopic linear thermal expansion and the lattice-parameter thermal expansion. The concentration fraction of native defects in thermal equilibrium at 1300 K is (3.6\ifmmode\pm\else\textpm\fi{}2.7)\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}7}$, or (1.8\ifmmode\pm\else\textpm\fi{}1.3)\ifmmode\times\else\texttimes\fi{}${10}^{16}$ atoms ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$. It is found that vacancies are predominant over interstitial atoms in concentration.

The influence of extracellular Ca2+ and Mg2+ concentrations ([Ca2+]ECF and [Mg2+]ECF, respectively) on central respiratory control was analyzed using the isolated brainstem–spinal cord of the neonatal rat. Central respiratory activity was recorded from the C4 ventral roots. The depth profile of [Ca2+]ECF below the ventral medullary surface was measured with ion-sensitive electrodes. The gradient in [Ca2+]ECF disappeared about 1 h after changing superfusate Ca2+ ([Ca2+]CSF) from 2 to 0.5 mM, but not even in 2 h after switching to Ca2+-free superfusate. High [Ca2+]CSF (4 mM) or high [Mg2+]CSF (4, 8 mM) decreased respiratory frequency (fR), whereas low [Ca2+]CSF (0.5 mM) increased fR and augmented the respiratory CO2 responsiveness. High [Ca2+]CSF as well as low [Mg2+]CSF (0.5 mM) disturbed respiratory rhythm and pattern, which were markedly restored by high CO2. The depressing effect of high [Ca2+]ECF and the stimulating effect of low [Ca2+]ECF on the medullary neuronal activity were confirmed by perforated patch recordings. These results suggest that [Ca2+]ECF and [Mg2+]ECF determine the excitability of the respiratory neuron network by modulating the neuronal surface potential, transmembrane Ca2+ influx, Ca2+-sensitive cation channel gating, and synaptic transmission. Furthermore, some of these actions appear to be antagonized by CO2/H+.

Scratch-induced mechanical damage on silicon (111) surfaces, in particular the fractures, residual strain fields and anneal-induced dislocations generated by and direction scratches, is investigated by optical microscopy, X-ray diffraction topography and the copper decoration method. The asymmetry in this damage in the [112̄] and reverse [1̄1̄2] directions is observed. The asymmetries are correlated with each other and are discussed in terms of the inclined (111̄) cleavage plane whose intersection with the (111) surface is perpendicular to the direction.

Asymmetry in indentation-induced mechanical damage on Si (111) surfaces is investigated by using optical microscopy and X-ray diffraction topography. Cracks, residual strain fields and anneal-induced dislocation rosettes around the indentation are found to represent the asymmetries in the [1̄1̄2] and reverse [112̄] directions on the (111) surface. The crack formation along three directions and the residual strain field distribution along directions are discussed in terms of dislocation reaction and silicon crystal structure, respectively.

Growth striations in a liquid encapusulated Czochralski (LEC) GaP crystal doped with Te at the concentration of 6×1017 cm-3 was examined by the 90°-angle light scattering method. The growth striations were manifested as a periodical fluctuation in the scattering intensity along the growth direction in the core region of the crystal. The striations were found to be clearly correlated with chemical etching pattern, periodical Te fluctuation detected by electron-probe X-ray microanalysis and periodical cathodoluminescence signal by Te donor. The origin of the striated scattering pattern is attributed to the periodical distribution of the scattering centers formed by the preferential precipitation of excess Te on grown-in dislocations.

In gallium arsenide single crystal grown by using a sealed ampoule procedure based on the vertical gradient freeze method, dislocation elimination with an increasing fraction of melt solidified was observed by chemical etching and X-ray topography. It is found that the dislocation density is as low as 103 cm-2 in the tail end of the 60-mm-long ingot. The mechanism of the reduction of dislocation densities is discussed in terms of the loop formation.

The lattice parameter of high‐purity silicon is measured as a function of temperature between 300 and 1500 K, and the linear thermal expansion coefficient is accurately determined. Precise measurements are made by the high‐temperature attachment for Bond’s x‐ray method to a few parts per million. It is found that the temperature dependence of the linear thermal expansion coefficient α(t) is empirically given by α(t)=(3.725{1−exp[−5.88×10−3{(t−124)} +5.548×10−4t)×10−6 (K−1), where t is the absolute temperature ranging from 120 to 1500 K. It is shown that the lattice parameter in the above temperature range can be calculated using α(t) and the lattice parameter at 273.2 K (0.5430741 nm). Measured values of the lattice parameter and the thermal expansion coefficient for high‐purity float‐zoned (100 kΩ cm) and Czochralski‐grown (30 Ω cm) single crystals are uniformly distributed within ±1×10−5 nm and ±2×10−7 K−1 with respect to the values obtained from the above empirical formula.

The effects of substrate temperature on the donor ionization energy and on the electrical and photoluminescent properties of selectively doped short‐period GaAs:Si/AlAs superlattices are studied. The superlattice structure is characterized by means of double‐crystal x‐ray diffraction. It is found that the interface between the GaAs and AlAs layers slightly degrades even at a low substrate temperature of 550 °C, and that the degradation is enhanced with an increase in the substrate temperature. The Si donor level is still shallow for substrate temperatures lower than 600 °C, since only a slight degradation occurs in this temperature range. However, the Si donor forms an excess deep DX center near the interface region for higher substrate temperatures. Accordingly, the donor binding energy increases with increasing substrate temperature, since the contribution from the mixed interface region becomes larger. With an increase in the substrate temperature, the photoluminescence peak intensity increases, althou...

Heating-up of bulk As-T-Ge glass by switching has been visualized for various stages during the delay time. The voltage and the current have been also recorded. A comparison of these results with the resistivity-temperature characteristic presents an evidence for thermal pinching.

We developed a dual oscillator model to facilitate the understanding of dynamic interactions between the parafacial respiratory group (pFRG) and the preBötzinger complex (preBötC) neurons in the respiratory rhythm generation. Both neuronal groups were modeled as groups of 81 interconnected pacemaker neurons; the bursting cell model described by Butera and others [model 1 in Butera et al. (J Neurophysiol 81:382–397, 1999a)] were used to model the pacemaker neurons. We assumed (1) both pFRG and preBötC networks are rhythm generators, (2) preBötC receives excitatory inputs from pFRG, and pFRG receives inhibitory inputs from preBötC, and (3) persistent Na+ current conductance and synaptic current conductances are randomly distributed within each population. Our model could reproduce 1:1 coupling of bursting rhythms between pFRG and preBötC with the characteristic biphasic firing pattern of pFRG neurons, i.e., firings during pre-inspiratory and post-inspiratory phases. Compatible with experimental results, the model predicted the changes in firing pattern of pFRG neurons from biphasic expiratory to monophasic inspiratory, synchronous with preBötC neurons. Quantal slowing, a phenomena of prolonged respiratory period that jumps non-deterministically to integer multiples of the control period, was observed when the excitability of preBötC network decreased while strengths of synaptic connections between the two groups remained unchanged, suggesting that, in contrast to the earlier suggestions (Mellen et al., Neuron 37:821–826, 2003; Wittmeier et al., Proc Natl Acad Sci USA 105(46):18000–18005, 2008), quantal slowing could occur without suppressed or stochastic excitatory synaptic transmission. With a reduced excitability of preBötC network, the breakdown of synchronous bursting of preBötC neurons was predicted by simulation. We suggest that quantal slowing could result from a breakdown of synchronized bursting within the preBötC. peerReviewed

By precise measurement of the spatial variation in the lattice parameters of {001} undoped Czochralski grown gallium arsenide wafers, it was found that the lattice parameters are strongly dependent upon elastic strain and not so much on the melt composition. Although a remarkable spatial variation in the lattice parameters of ±5×10−6 nm from the average value was observed in a wafer specimen, the variation was considerably reduced to ±2×10−6 nm by dividing the wafer into small specimens. The lattice parameter variation was smaller than 2×10−6 nm due to a change in the As composition ratio from 0.42 to 0.52 in the melt.

The dependence of sheet carrier concentration of a Si‐implanted layer on lattice parameters of undoped liquid encapsulated Czochralski GaAs was investigated. Crystals were grown from near‐stoichiometric melts with varying boron concentrations. Sheet carrier concentration increases with an increase in lattice parameters due to the reduced boron concentration. An anomalous reduction in the lattice parameter suggests that native defects such as BGa VAs are responsible for the increase in the occupancy of implanted Si atoms on As sites.

Temperature dependence of the threshold voltage for switching phenomenon was measured in amorphous materials both of AsxTeyGe10 and AsxTeySi10 systems. A simple experimental relationship Vth = K. exp[ C. (Tg − T)] was obtained, where Vth = d.c. threshold voltage for switching, Tg = glass transition temperature. Constant K different values for each system, while constant C has the same value in both systems.

Background The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis. Methods Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue. Results The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group. Conclusion These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

An anomalous reduction of lattice parameter is observed for undoped semi‐insulating liquid encapsulated Czochralski‐grown GaAs by precision lattice parameter measurements with the use of the bond method. The anomalous reduction is though to be due to the incorporation of residual boron from the B2O3 encapsulant. The reduction rate is about 2 times larger than the predicted rate for the boron concentration derived from Vegard’s law. Possible defect models for this phenomenon are discussed.