Phonons, and in particular surface acoustic wave phonons, have been proposed as a means to coherently couple distant solid-state quantum systems. Individual phonons in a resonant structure can be ...controlled and detected by superconducting qubits, enabling the coherent generation and measurement of complex stationary phonon states. We report the deterministic emission and capture of itinerant surface acoustic wave phonons, enabling the quantum entanglement of two superconducting qubits. Using a 2-millimeter-long acoustic quantum communication channel, equivalent to a 500-nanosecond delay line, we demonstrate the emission and recapture of a phonon by one superconducting qubit, quantum state transfer between two superconducting qubits with a 67% efficiency, and, by partial transfer of a phonon, generation of an entangled Bell pair with a fidelity of 84%.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
Summary
Background
Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult‐onset asthma ...in community‐based populations.
Objective
We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community‐based adult populations.
Methods
The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin‐specific IgE using ImmunoCAP.
Results
Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin‐specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin‐specific IgE level was identified as the major determinant factor for total IgE level.
Conclusions and Clinical Relevance
Staphylococcal enterotoxin sensitization was independently associated with adult‐onset asthma in adult community populations. Strong correlations between the enterotoxin‐specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.
One of the hallmarks of quantum physics is the generation of non-classical quantum states and superpositions, which has been demonstrated in several quantum systems, including ions, solid-state ...qubits and photons. However, only indirect demonstrations of non-classical states have been achieved in mechanical systems, despite the scientific appeal and technical utility of such a capability
, including in quantum sensing, computation and communication applications. This is due in part to the highly linear response of most mechanical systems, which makes quantum operations difficult, as well as their characteristically low frequencies, which hinder access to the quantum ground state
. Here we demonstrate full quantum control of the mechanical state of a macroscale mechanical resonator. We strongly couple a surface acoustic-wave
resonator to a superconducting qubit, using the qubit to control and measure quantum states in the mechanical resonator. We generate a non-classical superposition of the zero- and one-phonon Fock states and map this and other states using Wigner tomography
. Such precise, programmable quantum control is essential to a range of applications of surface acoustic waves in the quantum limit, including the coupling of disparate quantum systems
.
Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI ...misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Twenty one Wistar rats were given omeprazole orally or intravenously for 30 days, and caerulein as a positive control. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S-based profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. After long-term PPI exposure, the fecal microbial profile was altered and showed similarity to those observed in high-fat diet studies. The concentrations of several metabolites were also changed in various specimens. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes and metabolic change are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. More importantly, we observed biliary epithelial hyperplasia, which is an indicator of a high-fat diet.
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
db
/
m
and
db
/
db
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
db
/
db
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
db
/
db
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.
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
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.
Background and purpose
Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy ...has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation.
Methods
Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow‐up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed.
Results
In cross‐sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (β = −0.35, P = 0.009). The CASI scores correlated with temporo‐parietal PI (Pearson r range 0.3–0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74).
Conclusions
Cognitive performance in mild AD can be reflected by hypo‐perfusion of the temporo‐parietal region while frontal hypo‐perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.
PDF
