Buffer gas induced collision shift for the 88^{88}Sr 1S0−3P1\bf{^1S_0-^3P_1} clock transition

Precision saturation spectroscopy of the $^{88}{\rm Sr} ^1S_0-^3P_1$ is performed in a vapor cell filled with various rare gas including He, Ne, Ar, and Xe. By continuously calibrating the absolute frequency of the probe laser, buffer gas induced collision shifts of $\sim$kHz are detected with gas pressure of 1-20 mTorr. Helium gave the largest fractional shift of $1.6 \times 10^{-9} {\rm Torr}^{-1}$. Comparing with a simple impact calculation and a Doppler-limited experiment of Holtgrave and Wolf [Phys. Rev. A {\bf 72}, 012711 (2005)], our results show larger broadening and smaller shifting coefficient, indicating effective atomic loss due to velocity changing collisions. The applicability of the result to the $^1S_0-^3P_0$ optical lattice clock transition is also discussed

Mean Lung Pressure during Adult High-Frequency Oscillatory Ventilation: An Experimental Study Using a Lung Model

In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance: 19.3ml/cmH2O) with or without a resistor (20cmH2O/l/sec). The ventilator settings were as follows: mean airway pressure (MAP), 30cmH2O;frequency, 5-15Hz (every 1Hz);airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV

All-optical link for direct comparison of distant optical clocks

We developed an all-optical link system for making remote comparisons of two distant ultra-stable optical clocks. An optical carrier transfer system based on a fiber interferometer was employed to compensate the phase noise accumulated during the propagation through a fiber link. Transfer stabilities of $2\times10^{-15}$ at 1 second and $4\times10^{-18}$ at 1000 seconds were achieved in a 90-km link. An active polarization control system was additionally introduced to maintain the transmitted light in an adequate polarization, and consequently, a stable and reliable comparison was accomplished. The instabilities of the all-optical link system, including those of the erbium doped fiber amplifiers (EDFAs) which are free from phase-noise compensation, were below $2\times10^{-15}$ at 1 second and $7\times10^{-17}$ at 1000 seconds. The system was available for the direct comparison of two distant $^{87}$Sr lattice clocks via an urban fiber link of 60 km. This technique will be essential for the measuring the reproducibility of optical frequency standards

Stability Transfer between Two Clock Lasers Operating at Different Wavelengths for Absolute Frequency Measurement of Clock Transition in 87Sr

We demonstrated transferring the stability of one highly stable clock laser operating at 729 nm to another less stable laser operating at 698 nm. The two different wavelengths were bridged using an optical frequency comb. The improved stability of the clock laser at 698 nm enabled us to evaluate the systematic frequency shifts of the Sr optical lattice clock with shorter averaging time. We determined the absolute frequency of the clock transition 1S0 - 3P0 in 87Sr to be 429 228 004 229 873.9 (1.4) Hz referenced to the SI second on the geoid via International Atomic Time (TAI)

Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor

The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p＝0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p＝0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p＝0.049, and ＜0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy

Direct Comparison of Distant Optical Lattice Clocks at the 10−1610^{-16} Uncertainty

Fiber-based remote comparison of $^{87}$Sr lattice clocks in 24 km distant laboratories is demonstrated. The instability of the comparison reaches $5\times10^{-16}$ over an averaging time of 1000 s, which is two orders of magnitude shorter than that of conventional satellite links and is limited by the instabilities of the optical clocks. By correcting the systematic shifts that are predominated by the differential gravitational redshift, the residual fractional difference is found to be $(1.0\pm7.3)\times10^{-16}$, confirming the coincidence between the two clocks. The accurate and speedy comparison of distant optical clocks paves the way for a future optical redefinition of the second

No association of the Trp 64 Arg mutation of the β3-adrenergic receptor gene with obesity, type 2 diabetes mellitus, hyperlipidemia, and hypertension in Japanese patients with schizophrenia

This study was conducted to address the question of whether the β3-adrenergic receptor gene mutation (Trp 64 Arg) is associated with metabolic disease in Japanese patients with schizophrenia. Methods : In a cross-sectional study, 89 participants were grouped into three genotypes. The 64 Arg allelic frequency in patients with or without metabolic disease was analyzed. Anthropometrics variables and biochemical parameters were compared among the genotypes. Results : The 64 Arg allele, which had a frequency of 0.22, was not associated with obesity, type 2 diabetes mellitus, dyslipidemias, or hypertension. No significant differences among the genotypes were found in current age, age at diagnosis with schizophrenia, body mass index, waist-hip ratio, plasma glucose, plasma insulin, triglycerides, free fatty acids. Patients with the 64 Arg allele had greater 24-h excretion of norepinephrine than those lacking the variant (p=0.019). Conclusion : The 64Arg allelic mutation is not associated with obesity, type 2 diabetes mellitus, lipid metabolism dysfunction, or hypertension in Japanese patients with schizophrenia

Biomonitoring of Urinary Cotinine Concentrations Associated with Plasma Levels of Nicotine Metabolites after Daily Cigarette Smoking in a Male Japanese Population

Human biomonitoring of plasma and urinary levels of nicotine, cotinine, and 3′-hydroxycotinine was conducted after daily cigarette smoking in a population of 92 male Japanese smokers with a mean age of 37 years who had smoked an average of 23 cigarettes per day for 16 years. Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). The mean levels of nicotine, the levels of its metabolites cotinine and 3′-hydroxycotinine, and the sum of these three levels in subjects one hour after smoking the first cigarette on the sampling day were 20.1, 158, 27.7, and 198 ng/mL in plasma and 846, 1,020, 1,010, and 2,870 ng/mL in urine under daily smoking conditions. Plasma levels of 3′-hydroxycotinine and urinary levels of nicotine and 3′-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Plasma cotinine levels were significantly correlated with the number of cigarettes smoked on the day before sampling (r = 0.71), the average number of cigarettes smoked daily (r = 0.58), and the Brinkman index (daily cigarettes × years, r = 0.48) under the present conditions. The sum of nicotine, cotinine, and 3′-hydroxycotinine concentrations in plasma showed a similar relationship to that of the plasma cotinine levels. Urinary concentrations of cotinine and the sum of nicotine metabolite concentrations also showed significant correlations with the plasma levels and the previous day’s and average cigarette consumption. The numbers of cigarettes smoked per day by two subjects with self-reported light smoking habits were predicted by measuring the urinary cotinine concentrations and using linear regression equations derived from above-mentioned data. These results indicate that biomonitoring of the urinary cotinine concentration is a good, easy-to-use marker for plasma levels of cotinine and the sum of nicotine metabolites in smokers independent of genetic polymorphism of CYP2A6

Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity

Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation

Feasibility study of immediate pharyngeal cooling initiation in cardiac arrest patients after arrival at the emergency room

AIM: Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation. METHODS: Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min. RESULTS: There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P<0.001). The return of spontaneous circulation (70% vs. 65%, P=0.63) and rearrest (38% vs. 47%, P=0.45) rates were not significantly different based on the initiation of pharyngeal cooling. No post-treatment mechanical or cold-related injury was observed on the pharyngeal epithelium by macroscopic observation. The thrombocytopaenia incidence was lower in the pharyngeal cooling group (P=0.001) during the 3-day period after arrival. The cumulative survival rate at 1 month was not significantly different between the two groups. CONCLUSIONS: Initiation of pharyngeal cooling before or immediately after the return of spontaneous circulation is safe and feasible. Pharyngeal cooling can rapidly decrease tympanic temperature without adverse effects on circulation or the pharyngeal epithelium