Resolved atomic interaction sidebands in an optical clock transition

We report the observation of resolved atomic interaction sidebands (ISB) in the ${}^{87}$Sr optical clock transition when atoms at microkelvin temperatures are confined in a two-dimensional (2D) optical lattice. The ISB are a manifestation of the strong interactions that occur between atoms confined in a quasi-one-dimensional geometry and disappear when the confinement is relaxed along one dimension. The emergence of ISB is linked to the recently observed suppression of collisional frequency shifts in [1]. At the current temperatures, the ISB can be resolved but are broad. At lower temperatures, ISB are predicted to be substantially narrower and usable as powerful spectroscopic tools in strongly interacting alkaline-earth gases

Absolute frequency measurements with a robust, transportable ^{40}Ca^{+} optical clock

We constructed a transportable 40Ca+ optical clock (with an estimated minimum systematic shift uncertainty of 1.3*10^(-17) and a stability of 5*10^(-15)/sqrt{tau} ) that can operate outside the laboratory. We transported it from the Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan to the National Institute of Metrology, Beijing. The absolute frequency of the 729 nm clock transition was measured for up to 35 days by tracing its frequency to the second of International System of Units. Some improvements were implemented in the measurement process, such as the increased effective up-time of 91.3 % of the 40Ca+ optical clock over a 35-day-period, the reduced statistical uncertainty of the comparison between the optical clock and hydrogen maser, and the use of longer measurement times to reduce the uncertainty of the frequency traceability link. The absolute frequency measurement of the 40Ca+ optical clock yielded a value of 411042129776400.26 (13) Hz with an uncertainty of 3.2*10^(-16), which is reduced by a factor of 1.7 compared with our previous results. As a result of the increase in the operating rate of the optical clock, the accuracy of 35 days of absolute frequency measurement can be comparable to the best results of different institutions in the world based on different optical frequency measurements.Comment: 15 pages, 5 figure

Inhibitory mechanism of vortioxetine on CYP450 enzymes in human and rat liver microsomes

Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an in vitro incubation system of 200 μL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC50) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (Ki) values of 2.17 μM and 9.37 μM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its Ki values were 7.26 μM and 6.96 μM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with Ki values were 8.55 μM and 4.17 μM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (Ki = 4.41 and 100.9 μM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (Ki = 2.87 and 0.12 μM). The inhibition types of CYP2C-1 and CYP2C-3 (Ki = 39.91 and 4.23 μM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Joint Character-Level Word Embedding and Adversarial Stability Training to Defend Adversarial Text

Text classification is a basic task in natural language processing, but the small character perturbations in words can greatly decrease the effectiveness of text classification models, which is called character-level adversarial example attack. There are two main challenges in character-level adversarial examples defense, which are out-of-vocabulary words in word embedding model and the distribution difference between training and inference. Both of these two challenges make the character-level adversarial examples difficult to defend. In this paper, we propose a framework which jointly uses the character embedding and the adversarial stability training to overcome these two challenges. Our experimental results on five text classification data sets show that the models based on our framework can effectively defend character-level adversarial examples, and our models can defend 93.19% gradient-based adversarial examples and 94.83% natural adversarial examples, which outperforms the state-of-the-art defense models

The Role of Fluorescence In Situ Hybridization in the Surveillance of Non-Muscle Invasive Bladder Cancer: An Updated Systematic Review and Meta-Analysis

Background: Fluorescence in situ hybridization (FISH) has become a popular biomarker for subsequent monitoring the recurrence of non-muscle invasive bladder cancer (NMIBC), several studies have investigated the ability of FISH to detect recurrence in the surveillance of NMIBC. However, the results were inconsistent. Methods: We conducted a systematic literature search extensively on authenticated databases including PubMed/Medline, Embase, Web of Science, Ovid, and Cochrane Library. Meta-analysis was performed to find out the sensitivity and specificity of FISH in predicting recurrence of NMIBC. Results: 15 studies were ultimately included in this meta-analysis, a total of 2941 FISH evaluations from 2385 NMIBC patients were available. The pooled sensitivity of FISH was 68% (95% CI: 0.58–0.76), and the pooled specificity was 64% (95% CI: 0.53–0.74). Subgroup analyses were performed in 7 studies without Bacillus Calmette–Guerin (BCG) treatment, the pooled sensitivity was 82% (95% CI: 0.68–0.90), and the pooled specificity was 63% (95% CI: 0.37–0.82). And in 9 studies using “UroVysion standard” to define positive FISH results showed a pooled sensitivity of 60% (95% CI: 0.50–0.70) and specificity of 70% (95% CI: 0.61–0.78). Conclusions: The findings of this study indicate that FISH has a satisfactory sensitivity (68%) and specificity (64%) and could be a potential biomarker in the surveillance of NMIBC. Moreover, BCG treatment and different FISH methods may have an impact on the sensitivity and specificity, these factors should be taken into account when making clinical strategy