Testing Hypotheses of Covariate-Adaptive Randomized Clinical Trials

<div><p>Covariate-adaptive designs are often implemented to balance important covariates in clinical trials. However, the theoretical properties of conventional testing hypotheses are usually unknown under covariate-adaptive randomized clinical trials. In the literature, most studies are based on simulations. In this article, we provide theoretical foundation of hypothesis testing under covariate-adaptive designs based on linear models. We derive the asymptotic distributions of the test statistics of testing both treatment effects and the significance of covariates under null and alternative hypotheses. Under a large class of covariate-adaptive designs, (i) the hypothesis testing to compare treatment effects is usually conservative in terms of small Type I error; (ii) the hypothesis testing to compare treatment effects is usually more powerful than complete randomization; and (iii) the hypothesis testing for significance of covariates is still valid. The class includes most of the covariate-adaptive designs in the literature; for example, Pocock and Simon’s marginal procedure, stratified permuted block design, etc. Numerical studies are also performed to assess their corresponding finite sample properties. Supplementary material for this article is available online.</p></div

Predicting Energy Conversion Efficiency of Dye Solar Cells from First Principles

In this work we target on accurately predicting energy conversion efficiency of dye-sensitized solar cells (DSC) using parameter-free first principles simulations. We present a set of algorithms, mostly based on solo first principles calculations within the framework of density functional theory, to accurately calculate key properties in energy conversion including sunlight absorption, electron injection, electron–hole recombination, open circuit voltages, and so on. We choose two series of donor-π-acceptor dyes with detailed experimental photovoltaic data as prototype examples to show how these algorithms work. Key parameters experimentally measured for DSC devices can be nicely reproduced by first-principles with as less empirical inputs as possible. For instance, short circuit current of model dyes can be well reproduced by precisely calculating their absorption spectra and charge separation/recombination rates. Open circuit voltages are evaluated through interface band offsets, namely, the difference between the Fermi level of electrons in TiO₂ and the redox potential of the electrolyte, after modification with empirical formulas. In these procedures the critical photoelectron injection and recombination dynamics are calculated by real-time excited state electronic dynamics simulations. Estimated solar cell efficiency reproduces corresponding experimental values, with errors usually below 1–2%. Device characteristics such as light harvesting efficiency, incident photon-to-electron conversion efficiency, and the current–voltage characteristics can also be well reproduced and compared with experiment. Thus, we develop a systematic ab initio approach to predict solar cell efficiency and photovoltaic performance of DSC, which enables large-scale efficient dye screening and optimization through high-throughput first principles calculations with only a few parameters taken from experimental settings for electrode and electrolyte toward a renewable energy based society

Redox-Mediated Indirect Fluorescence Immunoassay for the Detection of Disease Biomarkers Using Dopamine-Functionalized Quantum Dots

Here, we report a redox-mediated indirect fluorescence immunoassay (RMFIA) for the detection of the disease biomarker α-fetoprotein (AFP) using dopamine (DA)-functionalized CdSe/ZnS quantum dots (QDs). In this immunoassay, tyrosinase was conjugated with the detection antibody and acted as a bridge connecting the fluorescence signals of the QDs with the concentration of the disease biomarkers. The tyrosinase label used for RMFIA catalyzed the enzymatic oxidation of DAs on the surface of functionalized QDs and caused fluorescence quenching in the presence of the analyte. Using this technique, we obtained a limit of detection as low as 10 pM for AFP. This assay’s potential for clinical analysis was demonstrated by detecting the real sera of patients with hepatocellular carcinoma (HCC). This study makes the first use of RMFIA for the rapid detection of AFP, opening up a new pathway for the detection of disease biomarkers

Monitoring Dopamine Quinone-Induced Dopaminergic Neurotoxicity Using Dopamine Functionalized Quantum Dots

Dopamine (DA) quinone-induced dopaminergic neurotoxicity is known to occur due to the interaction between DA quinone and cysteine (Cys) residue, and it may play an important a role in pathological processes associated with neurodegeneration. In this study, we monitored the interaction process of DA to form DA quinone and the subsequent Cys residue using dopamine functionalized quantum dots (QDs). The fluorescence (FL) of the QD bioconjugates changes as a function of the structure transformation during the interaction process, providing a potential FL tool for monitoring dopaminergic neurotoxicity

Alcohol Dehydrogenase-Catalyzed Gold Nanoparticle Seed-Mediated Growth Allows Reliable Detection of Disease Biomarkers with the Naked Eye

Here, we reported a strategy-based plasmonic enzyme-linked immunosorbent assay (ELISA) using alcohol dehydrogenase-catalyzed gold nanoparticle seed-mediated growth to serve as a colorimetric signal generation method for detecting disease biomarkers with the naked eye. This system possesses the advantages of outstanding robustness, sensitivity, and universality. By using this strategy, we investigated the hepatitis B surface antigen (HBsAg) and α-fetoprotein (AFP) with the lowest concentration of naked-eye detection down to 1.0 × 10^–12 g mL^–1. Experiments with real serum samples from HBsAg-infected patients are presented, demonstrating the potential for clinical analysis. Our method eliminates the need for sophisticated instruments and high detection expenses, making it possible to be a reliable alternative in resource-constrained regions

Single Ag Nanoparticle Electro-oxidation: Potential-Dependent Current Traces and Potential-Independent Electron Transfer Kinetic

Potential-dependent current traces were first observed for the same sized nanoparticles (NPs) during the dynamic electro-oxidation process of single AgNPs. In this work, we demonstrated that the motion trajectories of NPs, coupled with electrochemical kinetics parameters, qualitatively predicted from the series of the experimentally observed current traces obtained single AgNPs collision behaviors. Based on the Poisson–Boltzmann equation for a general electrochemical reaction, a rate constant of Ag oxidation could be further estimated to be 1 × 10^–6 mol·cm^–2·s^–1 for electron transfer between AgNPs and the Au electrode by comparing the experimental results. Our method provided a meaningful attempt to test electron transfer kinetics and motion behaviors of single NPs using the high-resolution electrochemical signal

Angular-Shaped Dithienonaphthalene-Based Nonfullerene Acceptor for High-Performance Polymer Solar Cells with Large Open-Circuit Voltages and Minimal Energy Losses

The utilization of low bandgap copolymers has been considered as one of the most efficient ways to increase power conversion efficiencies (PCEs) of fullerene-based polymer solar cells (PSCs). However, an increase in the short-circuit current (<i>J</i>_SC) value is usually counteracted by a decrease in the open-circuit voltage (<i>V</i>_OC), which limits a further PCE enhancement of fullerene-based PSCs. As a result, nonfullerene acceptors with wide-range tunable energy levels are used as alternatives to the traditional fullerene acceptors to overcome the negative trade-off between the <i>J</i>_SC and <i>V</i>_OC. Here, a novel nonfullerene acceptor is developed by using an angular-shaped dithienonaphthalene flanked by electron-withdrawing 3-ethylrhodanine units via benzothiadiazole bridges. The obtained nonfullerene acceptor exhibits a high-lying lowest unoccupied molecular orbital level of −3.75 eV with enhanced absorption. In combination with a benchmark low bandgap copolymer (PTB7-Th), a high PCE of 9.51% with a large <i>V</i>_OC of 1.08 V was achieved for the nonfullerene PSCs, demonstrating an extremely low energy loss of 0.50 eV, which is the lowest among all high-performance (PCE > 8%) polymer-based systems with similar optical bandgaps. The results demonstrate the bright future of our nonfullerene acceptor as an alternative to the fullerene derivatives for PSCs with large <i>J</i>_SC and <i>V</i>_OC values and improved device stability

Meikin synergizes with shugoshin to protect cohesin Rec8 during meiosis i

The conserved meiosis-specific kinetochore regulator, meikin (Moa1 in fission yeast) plays a central role in establishing meiosis-specific kinetochore function. However, the underlying molecular mechanisms remain elusive. Here, we show how Moa1 regulates centromeric cohesion protection, a function that has been previously attributed to shugoshin (Sgo1). Moa1 is known to associate with Plo1 kinase. We explore Plo1-dependent Rec8 phosphorylation and identify a key phosphorylation site required for cohesion protection. The phosphorylation of Rec8 by Moa1-Plo1 potentiates the activity of PP2A associated with Sgo1. This leads to dephosphorylation of Rec8 at another site, which thereby prevents cleavage of Rec8 by separase.</p

Divergent Reactivity in the Reaction of β‑Oxodithioesters and Hydroxylamine: Access to β‑Ketonitriles and Isoxazoles

Starting from β-oxodithioesters and hydroxylamine, two completely different transformations afford either β-ketonitriles or isoxazoles with high chemoselectivity depending on the reaction conditions. The reaction of β-oxodithioesters with hydroxylamine in EtOH at room temperature in daylight gave β-ketonitriles in high yields. On the other hand, 3-methylthio-isoxazoles were efficiently obtained as the final products by heating the mixture of β-oxodithioesters and hydroxylamine in HOAc at 90 °C

Palladium-Catalyzed Ylidyl-Carbonylation of Aryl Halides To Produce α‑Acylphosphoranes

An efficient synthesis of α-acylphosphoranes by palladium-catalyzed carbonylation of aryl iodides with carbon monoxide and stabilized phosphonium ylides has been developed. Featuring 44 examples, the protocol displayed a wide substrate scope under mild reaction conditions, showcasing its potential in synthetic organic chemistry