Spectroscopic Observations of the WZ Sge-Type Dwarf Nova GW Librae during the 2007 Superoutburst

We carried out an international spectroscopic observation campaign of the dwarf nova GW Librae (GW Lib) during the 2007 superoutburst. Our observation period covered the rising phase of the superoutburst, maximum, slowly decaying phase (plateau), and long fading tail after the rapid decline from the plateau. The spectral features dramatically changed during the observations. In the rising phase, only absorption lines of H$\alpha$, H$\beta$, and H$\gamma$ were present. Around the maximum, the spectrum showed singly-peaked emission lines of H$\alpha$, He I 5876, He I 6678, He II 4686, and C III/N III as well as absorption lines of Balmer components and He I. These emission lines significantly weakened in the latter part of the plateau phase. In the fading tail, all the Balmer lines and He I 6678 were in emission, as observed in quiescence. We find that the center of the H$\alpha$ emission component was mostly stable over the whole orbital phase, being consistent with the low inclination of the system. Comparing with the observational results of WZ Sge during the 2001 superoutburst, the same type of stars as GW Lib seen with a high inclination angle, we interpret that the change of the H$\alpha$ profile before the fading tail phase is attributed to a photoionized region formed at the outer edge of the accretion disk, irradiated from the white dwarf and inner disk.Comment: 10 pages, 9 figures, accepted for publication in PAS

Sleep status of older adults with sleep apnoea syndrome may vary by body mass index

Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI

In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer

EGFR mutated lung cancer accounts for a significant subgroup of non-small-cell lung cancer (NSCLC). Over the last decade, multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been developed to target mutated EGFR. However, there is little information regarding mutation specific potency of EGFR-TKIs against various types of EGFR mutations. The purpose of this study is to establish an in vitro model to determine the “therapeutic window” of EGFR-TKIs against various types of EGFR mutations, including EGFR exon 20 insertion mutations. The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR. An in vitro model of mutation specificity was created by calculating the ratio of IC50 values between mutated and wild type EGFR. The in vitro model identified a wide therapeutic window of afatinib for exon 19 deletions and L858R and of osimertinib and rociletinib for T790M positive mutations. The results obtained with our models matched well with previously reported preclinical and clinical data. Interestingly, for EGFR exon 20 insertion mutations, most of which are known to be resistant to 1st and 2nd generation EGFR-TKIS, osimertinib was potent and presented a wide therapeutic window. To our knowledge, this is the first report that has identified the therapeutic window of osimertinib for EGFR exon 20 insertion mutations. In conclusion, this model will provide a preclinical rationale for proper selection of EGFR-TKIs against clinically-relevant EGFR mutations

Safety of Postoperative Administration of Human Urinary Trypsin Inhibitor in Lung Cancer Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10(5), 6×10(5), and 9×10(5) units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.UMIN.ac.jp/ctr/UMIN000002410

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung

BackgroundAldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.MethodsWe examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice.ResultsIn humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 −/− and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 −/− mice. Aldh2 −/− tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 −/− mice than in WT mice.ConclusionsALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect

Carrier capture and escape processes in (In,Ga)N singlequantum-well diode under forward bias condition by photoluminescence spectroscopy

Carrier capture and escape processes in the super-bright green (In,Ga)N single-quantum-well (SQW)light-emitting diode (LED) has been studied by photoluminescence (PL) spectroscopy under reverse andforward bias conditions. The PL spectra were measured at 20 K under excitation photon energies aboveand below the bandgap energy of GaN barrier layers. The PL spectra under both excitation conditionsshow green emission from the (In,Ga)N SQW layer. The wavelength-integrated PL intensity changesdrastically depending on the applied bias voltage. For the excitation below the bandgap energy of GaN(direct excitation), the PL intensity increases with increasing the forward bias voltage up to +2 V and significantreduction of the PL intensity is observed with further increase of the forward bias voltage. On theother hand, for the excitation above the bandgap energy of GaN (indirect excitation), the PL intensity rapidlyincreases up to +2 V, decreases once, increases again with the maximum value at +3.25 V, and drasticallydecreases again. These differences of the PL intensity variation reflect carrier escape and captureprocesses. That is, in the direct excitation condition, the PL intensity variation indicates the effect of theelectric field on the radiative recombination and the carrier escape processes. In contrast, in the indirectexcitation condition, it is reflected in the carrier transfer and capture processes