A UV‐light‐emitting homojunction ZnO LED is grown by radiofrequency sputtering at high temperature, improving the structural, electrical, and optical properties of the n‐ and p‐type ZnO layers. The ...figure shows a comparison of the electroluminescence spectra of A) a p–n homojunction ZnO LED and B) a ZnO LED with Mg0.1Zn0.9O layers used as energy barrier layers. Such materials are of interest for their potential use in long‐lifetime solid‐state lighting, high‐density information storage, secure communication, and chemical/biological‐agent monitoring.
In acute myeloid leukemia (AML), about 25-30% of patients harbor a constitutively active receptor tyrosine kinase (RTK) FLT3 encoded by a FLT3 allele harboring internal tandem duplication (FLT3-ITD) ...mutation. The presence of FLT3-ITD correlates with poor prognosis in AML and it makes FLT3 an attractive therapeutic target in AML. Unfortunately, to date small-molecule inhibitors of FLT3 have resulted in only partial and transient clinical responses with residual leukemic blasts resistant to FLT3 inhibitors detected in blood or bone marrow. In this study, we investigated whether the RTK Axl is responsible for resistance of FLT3-ITD(+) AML cells to PKC412 and AC220, FLT3 inhibitors currently under clinical trials for FLT3-ITD(+) AML patients. Upon treatment with PKC412 or AC220, phosphorylation of Axl was significantly enhanced in the FLT3-ITD(+) MV4-11 AML cell line and in primary blasts from a FLT3-ITD(+) AML patient. Consistently, a PKC412-resistant AML cell line and PKC412-resistant primary blasts from FLT3-ITD(+) AML patients had significantly higher levels of constitutively phosphorylated Axl and total Axl when compared with a PKC412-sensitive AML cell line and PKC412-sensitive primary blasts from FLT3-ITD(+) AML patients. We also found that resistance of AML cells against the FLT3 inhibitor PKC412 and AC220 was substantially diminished by the inhibition of Axl via a small-molecule inhibitor TP-0903, a soluble receptor Axl fusion protein Axl-Fc or knockdown of Axl gene expression by shRNA. Collectively, our study suggests that Axl is required for resistance of FLT3-ITD(+) AML cells against the FLT3 inhibitor PKC412 and AC220, and that inhibition of Axl activation may overcome resistance to FLT3-targeted therapy in FLT3-ITD(+) AML.
Aim
To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)‐induced insulin‐deficient mice (STZ mice).
Methods
...Nine‐week‐old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.
Results
The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.
Conclusions
Our results show that LY2405319 reduces blood glucose levels in insulin‐deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.
Although surgical resection has been an important alternative treatment for patients with intractable epilepsy related to focal cortical dysplasia (FCD), the prognostic relevance of the degree of ...pathologic severity is controversial and there has been only limited information regarding the prognostic factors involved in the surgical treatment of refractory epilepsy in patients with FCD.
We undertook the present study to assess whether the pathologic subtypes of FCD affect surgical outcomes in patients with drug-resistant epilepsy. We also studied the prognostic roles of clinical factors and various diagnostic modalities in the surgical treatment.
A total of 166 consecutive patients were included. By univariate analysis, incomplete resection of epileptogenic area (p < 0.001), mild pathologic features (p = 0.01), and the presence of secondary tonic clonic seizures (2GTCS) (p = 0.05) were associated with poor surgical outcomes. There was a strong tendency for patients with severe pathologic features to have MRI abnormalities (p < 0.001). Incomplete resection of epileptogenic area (p < 0.001) and mild pathologic features (p = 0.02) were poor independent outcome predictors on multivariate analysis. The results of MRI, scalp EEG, fluorodeoxyglucose-PET, and ictal SPECT were not associated with surgical outcomes.
Our study shows that there is a strong tendency for patients with severe pathologic features to have MRI abnormalities, and patients with incomplete resection, mild pathologic features, or the presence of secondary tonic clonic seizures have a high chance of a poorer surgical outcome.
We conducted a 24‐week, multicentre, double‐blind, randomized study with a 28‐week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add‐on to metformin in patients ...with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were −0.85 ± 0.70% (p < 0.0001) for anagliptin and −0.83 ± 0.61% (p < 0.0001) for sitagliptin, with a mean difference of −0.02% (95% confidence interval of difference, −0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non‐inferiority of the efficacy of anagliptin to sitagliptin as an add‐on therapy was established with regard to efficacy and safety.
Kuroshio velocity structure and transport in the East China Sea (ECS) were investigated as part of a 23‐month study using inverted echo sounders and acoustic Doppler current profilers (ADCPs) along ...the regularly sampled PN‐line. Flow toward the northeast is concentrated near the continental shelf with the mean surface velocity maximum located 30 km offshore from the shelf break (taken as the 170 m isobath). There are two regions of southwestward flow: a deep countercurrent over the continental slope beneath the Kuroshio axis and a recirculation offshore which extends throughout the whole water column. There is a bimodal distribution to the depth of maximum velocity with occurrence peaks at the surface and 210 dbar. When the maximum velocity is located within the top 80 m of the water column, it ranges between 0.36 m/s and 2.02 m/s; when the maximum velocity is deeper than 80 m, it ranges between 0.31 m/s and 1.11 m/s. The 13‐month mean net absolute transport of the Kuroshio in the ECS is 18.5 ± 0.8 Sv (standard deviation, σ = 4.0 Sv). The mean positive and negative portions of this net flow are 24.0 ± 0.9 Sv and −5.4 ± 0.3 Sv, respectively.
LiteBIRD is a candidate satellite for a strategic large mission of JAXA. With its expected launch in the middle of the 2020s with a H3 rocket, LiteBIRD plans to map the polarization of the cosmic ...microwave background radiation over the full sky with unprecedented precision. The full success of LiteBIRD is to achieve
δ
r
<
0.001
, where
δ
r
is the total error on the tensor-to-scalar ratio
r
. The required angular coverage corresponds to
2
≤
ℓ
≤
200
, where
ℓ
is the multipole moment. This allows us to test well-motivated cosmic inflation models. Full-sky surveys for 3 years at a Lagrangian point L2 will be carried out for 15 frequency bands between 34 and 448 GHz with two telescopes to achieve the total sensitivity of 2.5
μ
K arcmin with a typical angular resolution of 0.5
∘
at 150 GHz. Each telescope is equipped with a half-wave plate system for polarization signal modulation and a focal plane filled with polarization-sensitive TES bolometers. A cryogenic system provides a 100 mK base temperature for the focal planes and 2 K and 5 K stages for optical components.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
Although perforation of the colon is known as one of the main complications of endoscopic submucosal dissection (ESD) for colorectal tumor management, factors predictive of perforation have not been ...fully evaluated. This study aimed to determine the factors associated with perforation during colorectal ESD.
Patients with colorectal tumors undergoing ESD were enrolled and their records were reviewed retrospectively. Age, sex, co-morbidity, medication history, procedure time, resection method, tumor size, location, gross morphology, the presence of fibrosis, and histologic findings were included as possible risk factors. In the cases where perforation had occurred, factors associated with the duration of hospitalization were analyzed.
One hundred eight lesions in 108 patients were eligible for inclusion in the study (68 patients were male; mean patient age was 63.01 ± 10.71 years). Mean tumor size was 27.59 ± 10.10 mm (range: 8 - 53 mm). Laterally spreading tumor was the most common type (75 %), followed by the protruding type (25 %). Procedure time was 61.95 ± 41.90 minutes (range: 5 - 198 minutes). Complete en bloc resection was achieved for 85 lesions (78.7 %). Perforation occurred in 22 patients (20.4 %). Multivariate analysis confirmed that tumor size odds ratio (OR): 1.084; 95 % confidence interval (CI): 1.015 - 1.158; P = 0.017 and the presence of fibrosis (OR: 4.551; 95 %CI: 1.092 - 18.960; P = 0.037) were independent risk factors for perforation. All cases of perforation were managed with nonsurgical treatment. Younger age and abdominal pain appeared to be related to prolonged hospitalization.
Tumor size and fibrosis are important factors related to complications during colorectal ESD. Younger age and development of abdominal pain can predict the hospital course in patients with perforation after ESD.
One of the important rotational resonances in nonaxisymmetric neoclassical transport has been experimentally validated in the KSTAR tokamak by applying highly nonresonant n=1 magnetic perturbations ...to rapidly rotating plasmas. These so-called bounce-harmonic resonances are expected to occur in the presence of magnetic braking perturbations when the toroidal rotation is fast enough to resonate with periodic parallel motions of trapped particles. The predicted and observed resonant peak along with the toroidal rotation implies that the toroidal rotation in tokamaks can be controlled naturally in favorable conditions to stability, using nonaxisymmetric magnetic perturbations.
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