Experimental Determination of the Gain Distribution of an Avalanche Photodiode at Low Gains

A measurement system for determining the gain distributions of avalanche photodiodes (APDs) in a low gain range is presented. The system is based on an ultralow-noise charge--sensitive amplifier and detects the output carriers from an APD. The noise of the charge--sensitive amplifier is as low as 4.2 electrons at a sampling rate of 200 Hz. The gain distribution of a commercial Si APD with low average gains are presented, demonstrating the McIntyre theory in the low gain range.Comment: 3 pages, 4 figure

Distinguishing genuine entangled two-photon-polarization states from independently generated pairs of entangled photons

A scheme to distinguish entangled two-photon-polarization states (ETP) from two independent entangled one-photon-polarization states (EOP) is proposed. Using this scheme, the experimental generation of ETP by parametric down-conversion is confirmed through the anti-correlations between three orthogonal two-photon-polarization states. The estimated fraction of ETP among the correlated photon pairs is 37% in the present experimental setup.Comment: 5 pages, 2 figure

Quantum receiver beyond the standard quantum limit of coherent optical communication

The most efficient modern optical communication is known as coherent communication and its standard quantum limit (SQL) is almost reachable with current technology. Though it has been predicted for a long time that this SQL could be overcome via quantum mechanically optimized receivers, such a performance has not been experimentally realized so far. Here we demonstrate the first unconditional evidence surpassing the SQL of coherent optical communication. We implement a quantum receiver with a simple linear optics configuration and achieve more than 90% of the total detection efficiency of the system. Such an efficient quantum receiver will provide a new way of extending the distance of amplification-free channels, as well as of realizing quantum information protocols based on coherent states and the loophole-free test of quantum mechanics.Comment: 5 pages, 3 figure

Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture

Neurons expressing neuropeptide orexins (hypocretins) in the lateral hypothalamus (LH) and serotonergic neurons in the dorsal raphe nucleus (DR) both play important roles in the regulation of sleep/wakefulness states, and show similar firing patterns across sleep/wakefulness states. Orexin neurons send excitatory projections to serotonergic neurons in the DR, which express both subtypes of orexin receptors (Mieda et al., 2011), while serotonin (5-HT) potently inhibits orexin neurons through activation of 5HT1A receptors (5HT1ARs). In this study, we examined the physiological importance of serotonergic inhibitory regulation of orexin neurons by studying the phenotypes of mice lacking the 5HT1A receptor gene (Htr1a) specifically in orexin neurons (ox5HT1ARKO mice). ox5HT1ARKO mice exhibited longer NREM sleep time along with decreased wakefulness time in the later phase of the dark period. We also found that restraint stress induced a larger impact on REM sleep architecture in ox5HT1ARKO mice than in controls, with a larger delayed increase in REM sleep amount as compared with that in controls, indicating abnormality of REM sleep homeostasis in the mutants. These results suggest that 5HT1ARs in orexin neurons are essential in the regulation of sleep/wakefulness states, and that serotonergic regulation of orexin neurons plays a crucial role in the appropriate control of orexinergic tone to maintain normal sleep/wake architecture

Exertional evaluation for BT

Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma. We evaluated the therapeutic effects of BT using cardiopulmonary exercise testing (CPET). After BT, the exercise time during CPET substantially prolonged reducing exertional dyspnea in the former (good), but not in the latter (poor). In the good responder, the high air remaining in the lung after expiration (i.e., inspiratory tidal volume minus expiratory tidal volume) during CPET decreased after BT. In contrast, in the poor responder, the high air remaining after expiration during exercise was not obtained before BT. Further investigations are necessary to confirm that the presence or absence of the exertional wasted ventilation on CPET may be informative to evaluate the therapeutic effects of BT

GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons

Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic "sleep-active" neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitatory influence on arousal-related neurons. It is important to know the anatomical and functional interactions between the POA sleep-active neurons and orexin neurons, both of which play important, but opposite roles in regulation of sleep/wakefulness states. In this study, we confirmed that specific pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase in the amount of non-rapid eye movement (NREM) sleep. We next examined direct connectivity between POA GABAergic neurons and orexin neurons using channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV-mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of orexin neurons. We found that these neurons send widespread projections to wakefulness-related areas in the hypothalamus and brain stem, including the LHA where these fibers make close appositions to orexin neurons. Optogenetic stimulation of these fibers resulted in rapid inhibition of orexin neurons. These observations suggest direct connectivity between POA GABAergic neurons and orexin neurons. © 2013 Saito, Tsujino, Hasegawa, Akashi, Abe, Mieda, Sakimura and Sakurai

Dyspnea and the Varying Pathophysiologic Manifestations of Chronic Obstructive Pulmonary Disease Evaluated by Cardiopulmonary Exercise Testing With Arterial Blood Analysis

Background: Patients with chronic obstructive pulmonary disease (COPD) show varying mechanisms of exertional dyspnea with different exercise capacities.Methods: To investigate the pathophysiologic conditions related to exertional dyspnea, 294 COPD patients were evaluated using cardiopulmonary exercise testing (CPET) with arterial blood analyses, with the patients classified into two groups according to their exercise limitation: the leg fatigue group (n = 58) and the dyspnea group (n = 215). The dyspnea group was further subdivided into four groups based on peak oxygen uptake (V°O2 in mL/min/kg): group A (< 11), group B (11 to < 15), group C (15 to < 21), and group D (≥21).Results: In the dyspnea group, group A (n = 28) showed the following findings: (i) the forced expiratory volume in 1 s was not correlated with the peak V°O2 (p = 0.288), (ii) the arterial oxygen tension (PaO2) slope (peak minus resting PaO2/ΔV°O2) was the steepest (p < 0.0001) among all subgroups, (iii) reduced tidal volume (VT) was negatively correlated with respiratory frequency at peak exercise (p < 0.0001), and (iv) a break point in exertional VT curve was determined in 17 (61%) patients in group A. In these patients, there was a significant negative correlation between bicarbonate ion (HCO3-) levels at peak exercise and VT level when the VT-break point occurred (p = 0.032). In group D (n = 46), HCO3- levels were negatively correlated with plasma lactate levels (p < 0.0001). In all subgroups, the HCO3- level was negatively correlated with minute ventilation. The dyspnea subgroups showed no significant differences in the overall mean pH [7.363 (SD 0.039)] and Borg scale scores [7.4 (SD, 2.3)] at peak exercise.Conclusions: During exercise, ventilation is stimulated to avoid arterial blood acidosis and hypoxemia, but ventilatory stimulation is restricted in the setting of reduced respiratory system ability. These conditions provoke the exertional dyspnea in COPD. Although symptom levels were similar, the exertional pathophysiologic conditions differed according to residual exercise performance; moreover, COPD patients showed great inter-individual variability. An adequate understanding of individual pathophysiologic conditions using CPET is essential for proper management of COPD patients

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions