Photonic-crystal surface-emitting lasers (PCSELs) use the two-dimensional (2D) resonance at the band-edge of a photonic crystal for lasing, and they feature various outstanding functionalities such ...as high-brightness lasing, arbitrary shaping of beam patterns and on-chip 2D beam steering. In this paper, to investigate the applicability of PCSELs for high-speed operation, we design PCSELs with enhanced in-plane optical feedback, which enable single-mode lasing inside a circular region the diameter of which is less than 10 µm. To realize a strong in-plane confinement of the lasing mode, we increase the one-dimensional coupling coefficients between counter-propagating waves through the careful design of the lattice points. We also introduce an in-plane heterostructure composed of two photonic crystals with different photonic bandgaps and utilize reflection at the boundary of the two photonic crystals in addition to the optical feedback at the band-edge of each photonic crystal. By using three-dimensional finite-difference time-domain method (3D-FDTD), we confirm that the proposed hetero-PCSELs can achieve single-mode lasing operation inside a 9-µm-diameter and possibly realize a 3-dB modulation bandwidth larger than 40 GHz.
Between 2001 and 2011, the standard of care for chronic hepatitis C virus (HCV) infection was a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). In May 2011, boceprevir and ...telaprevir, two first-generation NS3/4A protease inhibitors, were approved in combination with PEG-IFN and RBV for 24 to 48 weeks in hepatitis C virus genotype 1 infections. In December 2013, simeprevir, a second-generation NS3/4A protease inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotype 1, while sofosbuvir, a NS5B nucleotide polymerase inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotypes 1 and 4, as well as with RBV alone for 12 weeks in genotype 2 and for 24 weeks in genotype 3. Sofosbuvir combined with simeprevir or an NS5A replication complex inhibitor (ledipasvir or daclatasvir) with or without RBV for 12 weeks in genotype 1 resulted in a sustained virological response >90%, irrespective of previous treatment history or presence of cirrhosis. Similarly impressive sustained virological response rates have been shown with ABT-450/r (ritonavir-boosted NS3/4A protease inhibitor)-based regimens in combination with other direct-acting antiviral agent(s) with or without RBV for 12 weeks in genotype 1. The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS5A replication complex inhibitor with or without RBV. Further research is needed to determine the role of resistance testing, clarify the optimal follow-up duration post-treatment, and evaluate the antiviral efficacy and safety in difficult-to-cure patient populations.
Summary Objective We investigated the prevalence of radiographic knee osteoarthritis (OA) and knee pain in the Japanese elderly using a large-scale population of a nationwide cohort study, Research ...on Osteoarthritis Against Disability (ROAD), and examined their association. Methods From the baseline survey of the ROAD study, 2,282 participants ≥60 years (817 men and 1,465 women) living in urban, mountainous and seacoast communities were analyzed. The radiographic severity at both knees was determined by the Kellgren/Lawrence (KL) grading system. KL ≥ 2 and KL ≥ 3 knee OA were examined separately to assess osteophytosis and joint space narrowing (JSN). Results The prevalence of KL ≥ 2 OA (47.0% and 70.2% in men and women, respectively) was much higher than that of previous studies in Caucasians, while that of KL ≥ 3 OA was not much different in men. Age, BMI, female sex and rural residency were risk factors for radiographic knee OA, knee pain and their combination. The prevalence of knee pain was age-dependent in women, but not in men. Knee pain was more strongly associated with KL ≥ 3 OA than with KL = 2, and the association was higher in men than in women. Female sex was a strong risk factor even in the subgroup without radiographic knee OA (KL = 0/1). Conclusion The present cross-sectional study revealed a high prevalence of radiographic knee OA in the Japanese elderly. Knee pain was strongly associated with JSN especially in men, while women tended to have knee pain even without radiographic OA.
Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. Because of the ...variety of clinical manifestations, antemortem diagnosis of NIID is difficult.
Seven skin biopsy samples from patients with familial NIID were evaluated histochemically, and the results were compared with those of skin samples from normal control subjects and from patients with other neurologic diseases. We also examined skin biopsy samples from patients with NIID by electron microscopy.
In NIID skin biopsy samples, intranuclear inclusions were observed in adipocytes, fibroblasts, and sweat gland cells. These inclusions were stained with both anti-ubiquitin and anti-SUMO1 antibodies. Electron microscopy revealed that the features of the intranuclear inclusions in adipocytes, fibroblasts, and sweat gland cells were identical to those of neuronal cells. Approximately 10% of adipocytes showed intranuclear inclusions. No intranuclear inclusions were identified in the skin samples from normal control subjects and patients with other neurologic diseases.
Skin biopsy is an effective and less invasive antemortem diagnostic tool for NIID.
We studied the trapping of positive and negative charges in the chemical structures of polymers under a high electric field using a space charge measurement system. Positive charges accumulated in ...low-density polyethylene (LDPE), whereas positive and negative charges accumulated in polyimide (Kapton) and also in ethylene tetrafluoroethylene (ETFE) subjected to electron beam irradiation. To determine the charge-trapping sites in the chemical structures, a quantum chemical calculation was carried out using Density Function Theory (DFT) with Gaussian 09. The relationship between the energy band and the isosurface of orbital electrons at various energy levels was obtained. A three-dimensional (3D) electrostatic potential distribution map was obtained for positively and negatively charged polymers to determine the relationship between a trapping site and the charge accumulation center in the 3D potential distribution map. Positive and negative charges in Kapton and ETFE films are trapped in trapping sites in chemical structures and the positive charges in an LDPE film are trapped in physical defects.
We evaluated the effect of sustained virologic response (SVR) from direct‐acting antiviral (DAA)‐ and interferon‐based treatments on hepatocellular carcinoma (HCC) risk in a large population‐based ...cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon‐based treatments, followed for a median of 1.0 range: 0.6‐2.7 and 7.9 range: 4.4‐17.1 years, respectively. A total of 3613 and 6575 achieved SVR with DAAs‐ and interferon‐based treatments, respectively. Among DAAs‐treated patients, HCC incidence rate was 6.9 (95%CI: 4.7‐10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6‐71.0) in the no‐SVR group (HCC cases: 10, P < .001). Among interferon‐treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5‐2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3‐15.8) in the no‐SVR group (HCC cases: 239, P < .001). Compared with no‐SVR from interferon, SVR from DAA‐ and interferon‐based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19‐0.48 and adjSHR interferon = 0.2, 95%CI: 0.16‐0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51‐1.71). In conclusion, similar to interferon era, DAA‐related SVR is associated with 70% reduction in HCC risk.
Background and purpose:
5α,8α‐Epidioxy‐22E‐ergosta‐6, 22‐dien‐3β‐ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of ...action has yet to be determined. Here, we examine the anticancer and anti‐inflammatory effects of ergosterol peroxide.
Experimental approach:
After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS‐induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT‐PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells.
Key results:
Ergosterol peroxide suppressed LPS‐induced TNF‐α secretion and IL‐1α/β expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS‐induced DNA binding activity of NF‐κB and C/EBPβ, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down‐regulated the expression of low‐density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG‐CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress‐inducible genes, and the cyclin‐dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon‐inducible genes.
Conclusion and Implication:
Our results suggest that ergosterol peroxide and ergosterol suppress LPS‐induced inflammatory responses through inhibition of NF‐κB and C/EBPβ transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells.
British Journal of Pharmacology (2007) 150, 209–219. doi:10.1038/sj.bjp.0706972
Fillet yield (FY) and harvest weight (HW) are economically important traits in Nile tilapia production. Genetic improvement of these traits, especially for FY, are lacking, due to the absence of ...efficient methods to measure the traits without sacrificing fish and the use of information from relatives to selection. However, genomic information could be used by genomic selection to improve traits that are difficult to measure directly in selection candidates, as in the case of FY. The objectives of this study were: (i) to perform genome-wide association studies (GWAS) to dissect the genetic architecture of FY and HW, (ii) to evaluate the accuracy of genotype imputation and (iii) to assess the accuracy of genomic selection using true and imputed low-density (LD) single nucleotide polymorphism (SNP) panels to determine a cost-effective strategy for practical implementation of genomic information in tilapia breeding programs. The data set consisted of 5,866 phenotyped animals and 1,238 genotyped animals (108 parents and 1,130 offspring) using a 50K SNP panel. The GWAS were performed using all genotyped and phenotyped animals. The genotyped imputation was performed from LD panels (LD0.5K, LD1K and LD3K) to high-density panel (HD), using information from parents and 20% of offspring in the reference set and the remaining 80% in the validation set. In addition, we tested the accuracy of genomic selection using true and imputed genotypes comparing the accuracy obtained from pedigree-based best linear unbiased prediction (PBLUP) and genomic predictions. The results from GWAS supports evidence of the polygenic nature of FY and HW. The accuracy of imputation ranged from 0.90 to 0.98 for LD0.5K and LD3K, respectively. The accuracy of genomic prediction outperformed the estimated breeding value from PBLUP. The use of imputation for genomic selection resulted in an increased relative accuracy independent of the trait and LD panel analyzed. The present results suggest that genotype imputation could be a cost-effective strategy for genomic selection in Nile tilapia breeding programs.
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