Landau-Zener (LZ) transition has received renewed interest as an alternative approach to control single-qubit states. An LZ transition occurs when a system passes through an avoided crossing that ...arises from quantum mechanical coupling of two levels, taking the system to a coherent superposition of the two states. Then, multiple LZ transitions induce interference known as Landau-Zener-Stückelberg (LZS) interference whose amplitude strongly depends on the velocity or adiabaticity of the passage. Here, we study the roles of LZ transitions and LZS interference in coherent charge oscillations of a one-electron semiconductor double quantum dot by time-domain experiments using standard rectangular voltage pulses. By employing density matrix simulations, we show that, in the standard setup using rectangular pulses, even a small distortion of the pulse can give rise to LZ transitions and hence LZS interference, which significantly enhances the measured oscillation amplitude. We further show experimentally that the nature of the coherent charge oscillations changes from Rabi-type to LZS oscillations with increasing pulse distortion. Our results thus demonstrate that it is essential to take into account LZS interference for both precise control of charge qubits and correct interpretation of measurement results.
The angiotensin II (ANG II)-ANG II type 1 receptor (AT
R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT
R axis via ...converting ANG II to angiotensin 1-7 (Ang 1-7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1-7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg
·day
) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1-7 axis represent a potential therapeutic approach to prevent the development of obesity.
Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may ...have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.
The identification of acquired resistance mutations has been essential in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) active mutations. Rebiopsy plays a ...pivotal role in selecting the optimal treatment for patients who develop resistance to initial EGFR-tyrosine kinase inhibitors (EGFR-TKIs). This multicenter, observational study was conducted to investigate the details of rebiopsy in Japanese clinical practice. The primary endpoints were the implementation rate of rebiopsy and the concordance rate for T790M mutation detection between histological and cytological specimens using the cobas EGFR Mutation Test, version 2. One hundred ninety-four patients with EGFR-mutant NSCLC were enrolled, and 120 patients developed acquired resistance to EGFR-TKIs. The median age was 68 years (range 20-87), and 52.5% of the patients were women. Rebiopsy was performed in 109 patients, and the implementation rate of rebiopsy was 90.8%. The success rates of rebiopsy in the total, histology, cytology and liquid biopsy populations were 67.9%, 81.3%, 66.7% and 43.8%, respectively. The positive percent agreement and the negative percent agreement in the detection of the T790M mutation between the histological and cytological specimens were both 90.9%. Obtaining histological or cytological tissue samples at rebiopsy may contribute to improving the detection rate of the T790M mutation (trial registration number: UMIN000026019).
Nocardiosis is known as an opportunistic infection in immunocompromised hosts, but it occasionally has been reported in immunocompetent patient. The Nocardia exalbida is first-reported in 2006 from ...Japan, and a few cases of have been reported in only immunocompromised host, and the characteristic is still unclear. We herein describe the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. we reported the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. N. exalbida infection might be associated with a good response to treatment.
To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency.
A retrospective cohort study was ...conducted in 34 pediatric patients diagnosed with vitamin D deficiency/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored.
The median age at the first visit was significantly lesser in the BL group (1.58 years old interquartile range (IQR): 1.33, 2.17) than that in the non-BL group (3.00 years old IQR: 2.33, 3.67). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 IQR: -2.63, -1.94) than that in the BL group (-1.37 IQR: -1.91, -1.07). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group.
The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.
Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. ...We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.
•We studied cadmium (Cd) adsorption and partitioning in wheat varieties (Triticum aestivum).•In a pot experiment, Cd absorption was lower in varieties with low grain Cd.•Wheat varieties differed in ...Cd sequestration at various plant parts.•Remobilization from shoots and direct transport from roots affect grain Cd levels.•Xylem and phloem transport both affect Cd accumulation.
Low cadmium (Cd) transfer from the soil to edible parts of crop plants is important to minimize toxicity to humans and animals. We previously showed that Cd accumulation in grains differs substantially among varieties of common wheat (Triticum aestivum L.). In this study, we investigated the factors responsible for these differences by comparing the absorption and partitioning of Cd among wheat varieties with distinct grain Cd concentrations. Three varieties with low grain Cd concentrations (low-Cd/G varieties) and one standard variety were cultivated in a field (under natural conditions) and in pots with Cd application at four growth stages (emergence, jointing, flowering, and grain-filling). The Cd concentration and content in the whole plant and grains were determined at the seedling, flowering, grain-filling, and maturity stages in the field experiment. Cd concentration, content, and partitioning in different plant segments were determined at the maturity stage in the pot experiment. In the field experiment, there were significant differences in Cd partitioning to grains between low-Cd/G varieties and the standard variety. Cd application at different growth stages in the pot experiment indicated the remobilization of Cd from shoots to grains and direct transport of Cd from roots to grains. In the pot experiment, lower Cd absorption was detected in low-Cd/G varieties than in the standard variety and the low-Cd/G varieties exhibited differences in Cd sequestration among plant parts, including the root, leaf, lower stem, first internode, rachis, and/or glume. These results suggest that several factors related to Cd absorption and translocation, such as root traits and xylem and phloem transport, affect the accumulation of Cd in grains in common wheat. Understanding and elucidating the contribution of each of these factors might facilitate the development of common wheat varieties with minimal grain Cd accumulation.
Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are ...available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2(nd) EGFR-TKI administration.
We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.
Three patients (27%) were treated with gefitinib as the 2(nd) EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2(nd) EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2(nd) EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2(nd) EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.
Our results indicate that a 2(nd) EGFR-TKI treatment can be an effective treatment option for gefitinib responders.
Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was ...unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.
•Erythropoietin and darbepoetin alpha, a long acting ESA, ameliorate NAFLD.•Erythropoietin and darbepoetin alpha suppress lipogenesis in liver.•Erythropoietin and darbepoetin alpha increase lipolysis in visceral WAT.•This mechanism may be via EPO/EPOR-induced STAT3 and STAT5 activation.•Darbepoetin alpha shows almost same metabolic effect as erythropoietin.
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