Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.
All-inorganic perovskite solar cells (pero-SCs) are attracting considerable attention due to their promising thermal stability, but their inferior power-conversion efficiency (PCE) and moisture instability are hindering their application. Here, we used a gradient thermal annealing (GTA) method to control the growth of a-CsPbI 2 Br crystals and then utilized a green anti-solvent (ATS) isopropanol to further optimize the morphology of a-CsPbI 2 Br film. Through this GTA-ATS synergetic effect, the growth of a-CsPbI 2 Br crystals could be precisely controlled, leading to a high-quality perovskite film with one-micron average grain size, low root-mean-square of 25.9 nm, and reduced defect density. Pero-SCs based on this CsPbI 2 Br film achieved a champion scan PCE of 16.07% (stabilized efficiency of 15.75%), which is the highest efficiency reported in all-inorganic pero-SCs. Moreover, the CsPbI 2 Br pero-SC demonstrates excellent robustness against moisture and oxygen, and maintains 90% of initial PCE after aging 120 hr under 100 mW/cm 2 UV irradiation.
Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.
Automated image analysis aims to extract relevant information from contrast-enhanced magnetic resonance images (CE-MRI) of the breast and improve the accuracy and consistency of image interpretation. In this work, we extend the traditional 2D gray-level co-occurrence matrix (GLCM) method to investigate a volumetric texture analysis approach and apply it for the characterization of breast MR lesions. Our database of breast MR images was obtained using a T1-weighted 3D spoiled gradient echo sequence and consists of 121 biopsy-proven lesions (
The area under the receiver operating characteristic (ROC) curve (AUC) is often used as a summary index of the diagnostic ability in evaluating biomarkers when the clinical outcome (truth) is binary. When the clinical outcome is right-censored survival time, the C index, motivated as an extension of AUC, has been proposed by Harrell as a measure of concordance between a predictive biomarker and the right-censored survival outcome. In this work, we investigate methods for statistical comparison of two diagnostic or predictive systems, of which they could either be two biomarkers or two fixed algorithms, in terms of their C indices. We adopt a U-statistics based C estimator that is asymptotically normal and develop a nonparametric analytical approach to estimate the variance of the C estimator and the covariance of two C estimators. A z-score test is then constructed to compare the two C indices. We validate our one-shot nonparametric method via simulation studies in terms of the type I error rate and power. We also compare our one-shot method with resampling methods including the jackknife and the bootstrap. Simulation results show that the proposed one-shot method provides almost unbiased variance estimations and has satisfactory type I error control and power. Finally, we illustrate the use of the proposed method with an example from the Framingham Heart Study.
Organic solar cells (OSCs) can be unstable under ultraviolet (UV) irradiation. To address this issue and enhance the power conversion efficiency (PCE), an inorganic-perovskite/organic four-terminal tandem solar cell (TSC) based on a semitransparent inorganic CsPbBr perovskite solar cell (pero-SC) as the top cell and an OSC as bottom cell is constructed. The high-quality CsPbBr photoactive layer of the planar pero-SC is prepared with a dual-source vacuum coevaporation method, using stoichiometric precursors of CsBr and PbBr with a low evaporation rate. The resultant opaque planar pero-SC exhibits an ultrahigh open-circuit voltage of 1.44 V and the highest reported PCE of 7.78% for a CsPbBr -based planar pero-SC. Importantly, the devices show no degradation after 120 h UV light illumination. The related semitransparent pero-SC can almost completely filter UV light and well maintain photovoltaic performance; it additionally shows an extremely high average visible transmittance. When it is used to construct a TSC, the top pero-SC acting as a UV filter can utilize UV light for photoelectric conversion, avoiding the instability problem of UV light on the bottom OSC that can meet the industrial standards of UV-light stability for solar cells, and leading to the highest reported PCE of 14.03% for the inorganic-perovskite/organic TSC.
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