An outstanding goal in quantum optics and scalable photonic quantum technology is to develop a source that each time emits one and only one entangled photon pair with simultaneously high entanglement ...fidelity, extraction efficiency, and photon indistinguishability. By coherent two-photon excitation of a single InGaAs quantum dot coupled to a circular Bragg grating bull's-eye cavity with a broadband high Purcell factor of up to 11.3, we generate entangled photon pairs with a state fidelity of 0.90(1), pair generation rate of 0.59(1), pair extraction efficiency of 0.62(6), and photon indistinguishability of 0.90(1) simultaneously. Our work will open up many applications in high-efficiency multiphoton experiments and solid-state quantum repeaters.
Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including ...the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.
•To reflect the environmental sensitivity of Vehicle Routing Problem (VRP).•To review the studies on VRP in energy consumption, emissions, reverse logistics.•To identify Green Vehicle Routing Problem ...(GVRP) and its classification.•To suggest the future research directions in GVRP.
Green Logistics has emerged as the new agenda item in supply chain management. The traditional objective of distribution management has been upgraded to minimizing system-wide costs related to economic and environmental issues. Reflecting the environmental sensitivity of vehicle routing problems (VRP), an extensive literature review of Green Vehicle Routing Problems (GVRP) is presented. We provide a classification of GVRP that categorizes GVRP into Green-VRP, Pollution Routing Problem, VRP in Reverse Logistics, and suggest research gaps between its state and richer models describing the complexity in real-world cases. The purpose is to review the most up-to-date state-of-the-art of GVRP, discuss how the traditional VRP variants can interact with GVRP and offer an insight into the next wave of research into GVRP. It is hoped that OR/MS researchers together with logistics practitioners can be inspired and cooperate to contribute to a sustainable industry.
The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room ...temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12–14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.
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Through-silicon via (TSV) has been used for 3-dimentional integrated circuits. Mechanical stresses in Cu and Si around the TSV were measured using synchrotron X-ray microdiffraction. ...The hydrostatic stress in Cu TSV went from high tensile of 234MPa in the as-fabricated state, to −196MPa (compressive) during thermal annealing (in situ measurement), to 167MPa in the post-annealed state. Due to this stress, the keep-away distance in Si was determined to be about 17μm. Our results suggest that Cu stress may lead to reliability as well as integration issues, while Si stress may lead to device performance concerns.
There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have ...failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10mg/kg by intravenous infusion every 2weeks or physician’s choice of chemotherapy (paclitaxel 80mg/m2 on days 1, 8, and 15 or irinotecan 150mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0months; hazard ratio (HR)=1.1 95% confidence interval (CI) 0.9–1.4; P=0.81} or the secondary end points of PFS median, 1.4 versus 2.7months; HR=1.73 (95% CI 1.4–2.2); P>0.99 or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
ClinicalTrials.gov: NCT02625623.
This paper presents a comprehensive study on the influences of parasitic elements on the MOSFET switching performance. A circuit-level analytical model that takes MOSFET parasitic capacitances and ...inductances, circuit stray inductances, and reverse current of the freewheeling diode into consideration is given to evaluate the MOSFET switching characteristics. The equations derived for emulating MOSFET switching transients are assessed graphically, which, compared to results obtained merely from simulation or parametric study, can offer better insight into where the changes in switching performance lie when the parasitic elements are varied. The analysis has been successfully substantiated by the experimental results of a 400 V, 6 A test bench. A discussion on the physical meanings behind these parasitic effect phenomena is included. Knowledge about the effects of parasitic elements on the switching behavior serves as an important basis for the design guidelines of fast switching power converters.
Traditional multiobjective evolutionary algorithms (MOEAs) consider multiple objectives as a whole when solving multiobjective optimization problems (MOPs). However, this consideration may cause ...difficulty to assign fitness to individuals because different objectives often conflict with each other. In order to avoid this difficulty, this paper proposes a novel coevolutionary technique named multiple populations for multiple objectives (MPMO) when developing MOEAs. The novelty of MPMO is that it provides a simple and straightforward way to solve MOPs by letting each population correspond with only one objective. This way, the fitness assignment problem can be addressed because the individuals' fitness in each population can be assigned by the corresponding objective. MPMO is a general technique that each population can use existing optimization algorithms. In this paper, particle swarm optimization (PSO) is adopted for each population, and coevolutionary multiswarm PSO (CMPSO) is developed based on the MPMO technique. Furthermore, CMPSO is novel and effective by using an external shared archive for different populations to exchange search information and by using two novel designs to enhance the performance. One design is to modify the velocity update equation to use the search information found by different populations to approximate the whole Pareto front (PF) fast. The other design is to use an elitist learning strategy for the archive update to bring in diversity to avoid local PFs. CMPSO is comprehensively tested on different sets of benchmark problems with different characteristics and is compared with some state-of-the-art algorithms. The results show that CMPSO has superior performance in solving these different sets of MOPs.
Aims/hypothesis
Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome ...proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes.
Methods
Four groups of male C57BLKS/J
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mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks.
Results
The
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mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1–PGC-1α signalling and of the key downstream effectors, the PPARα–oestrogen-related receptor (ERR)-1α–sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)–Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1–PGC-1α signalling and the downstream effectors, PPARα–ERR-1α–SREBP1.
Conclusions/interpretation
The results suggest that resveratrol prevents diabetic nephropathy in
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mice by the phosphorylation of AMPK and activation of SIRT1–PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.
We present the first highly resolved measurements of the plasmon spectrum in an ultrafast heated solid. Multi-keV x-ray photons from the Linac Coherent Light Source have been focused to one ...micrometer diameter focal spots producing solid density aluminum plasmas with a known electron density of n_{e}=1.8×10^{23} cm^{-3}. Detailed balance is observed through the intensity ratio of up- and down-shifted plasmons in x-ray forward scattering spectra measuring the electron temperature. The plasmon damping is treated by electron-ion collision models beyond the Born approximation to determine the electrical conductivity of warm dense aluminum.
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