Development of an Aptamer-Conjugated Polyrotaxane-Based Biodegradable Magnetic Resonance Contrast Agent for Tumor-Targeted Imaging

Gadolinium-based magnetic resonance imaging (MRI) contrast agents with biodegradability, biosafety, and high efficiency are highly desirable for tumor diagnosis. Herein, a biodegradable, AS1411-conjugated, α-cyclodextrin polyrotaxane-based MRI contrast agent (AS1411-G2­(DTPA-Gd)-SS-PR) was developed for targeted imaging of cancer. The polyrotaxane-based contrast agent was achieved by the complexation of α-cyclodextrin (α-CD) and a linear poly­(ethylene glycol) (PEG) chain containing disulfide linkages at two terminals. The disulfides enable the dethreading of the polyrotaxane into excretable small units due to cleavage of the disulfide linkages by reducing agents such as intracellular glutathione (GSH). Furthermore, the second-generation lysine dendron conjugated with gadolinium chelates and AS1411, a G-quadruplex oligonucleotide that has high binding affinity to nucleolin generally presenting a high level on the surface of tumor cells, coupled to the α-CD via click chemistry. The longitudinal relaxivity of AS1411-G2­(DTPA-Gd)-SS-PR (11.7 mM–1 s–1) was two times higher than the clinically used Gd-DTPA (4.16 mM–1 s–1) at 0.5 T. The in vitro degradability was confirmed by incubating with 10 mM 1,4-dithiothreitol (DTT). Additionally, the cytotoxicity, histological assessment, and gadolinium retention studies showed that the prepared polyrotaxane-based contrast agent had a superior biocompatibility and was predominantly cleared renally without long-term accumulation toxicity. Importantly, AS1411-G2­(DTPA-Gd)-SS-PR displayed the enhanced performance in MRI of breast cancer cells in vitro as well as a subcutaneous breast tumor in vivo due to the targeting ability of the AS1411 aptamer. The enhanced performance was due to efficient multivalent interactions with tumor cells, producing faster accumulation and longer contrast imaging time at the tumor site. This work clearly confirms that the specially designed and fabricated α-CD-based polyrotaxane is a promising contrast agent with an excellent contrast imaging performance and biosafety for tumor MR imaging

To see or not to see: investigating detectability of Ganges River dolphins using a combined visual-acoustic survey

Detection of animals during visual surveys is rarely perfect or constant, and failure to account for imperfect detectability affects the accuracy of abundance estimates. Freshwater cetaceans are among the most threatened group of mammals, and visual surveys are a commonly employed method for estimating population size despite concerns over imperfect and unquantified detectability. We used a combined visual-acoustic survey to estimate detectability of Ganges River dolphins (Platanista gangetica gangetica) in four waterways of southern Bangladesh. The combined visual-acoustic survey resulted in consistently higher detectability than a single observer-team visual survey, thereby improving power to detect trends. Visual detectability was particularly low for dolphins close to meanders where these habitat features temporarily block the view of the preceding river surface. This systematic bias in detectability during visual-only surveys may lead researchers to underestimate the importance of heavily meandering river reaches. Although the benefits of acoustic surveys are increasingly recognised for marine cetaceans, they have not been widely used for monitoring abundance of freshwater cetaceans due to perceived costs and technical skill requirements. We show that acoustic surveys are in fact a relatively cost-effective approach for surveying freshwater cetaceans, once it is acknowledged that methods that do not account for imperfect detectability are of limited value for monitoring

Realization and Properties of Biochemical-Computing Biocatalytic XOR Gate Based on Enzyme Inhibition by a Substrate

We consider a realization of the XOR logic gate in a process biocatalyzed by an enzyme (here horseradish peroxidase: HRP), the function of which can be inhibited by a substrate (hydrogen peroxide for HRP), when the latter is inputted at large enough concentrations. A model is developed for describing such systems in an approach suitable for evaluation of the analog noise amplification properties of the gate. The obtained data are fitted for gate quality evaluation within the developed model, and we discuss aspects of devising XOR gates for functioning in "biocomputing" systems utilizing biomolecules for information processing

Two-Stage Optimization Model of Centralized Energy Storage Participating in Peak Shaving with Maximum Reserve Capacity and Minimum Carbon Emission of the System

As the proportion of renewable energy increases in power systems, the need for peak shaving is increasing. The optimal operation of the battery energy storage system (BESS) can provide a resilient and low-carbon peak-shaving approach for the system. Therefore, a two-stage optimization model for grid-side BESS is proposed. First, the carbon emission model of thermal power units considering BESS is proposed to describe the ability of the BESS in reducing the carbon emissions. Second, in order to deal with the uncertainty of the photovoltaics and wind forecast errors, a certain capacity of BESS is reserved. The model in the first stage takes the lowest carbon emission of the system as the goal, and the model in the second stage determines the BESS reserve capacity with the objective of minimizing the risk cost of the system. The simulation results show that the carbon emission model of thermal power units with BESS can measure the contribution of energy storage to emission reduction. By setting the reserve capacity of energy storage, the peak-shaving resilience of the system is improved, and the risk of photovoltaics and wind forecast error is reduced

The Research on the Signal Generation Method and Digital Pre-Processing Based on Time-Interleaved Digital-to-Analog Converter for Analog-to-Digital Converter Testing

In the high-resolution analog circuit, the performance of chips is an important part. The performance of the chips needs to be determined by testing. According to the test requirements, stimulus signal with better quality and performance is necessary. The main research direction is how to generate high-resolution and high-speed analog signal when there is no suitable high-resolution and high-speed digital-to-analog converter (DAC) chip available. In this paper, we take the high-resolution analog-to-digital converter (ADC) chips test as an example; this article uses high-resolution DAC chips and multiplexers to generate high-resolution high-speed signals that can be used for testing high-resolution ADC chips based on the principle of time-alternating sampling. This article explains its method, analyzes its error and proposes a digital pre-processing method to reduce the error. Finally, the actual circuit is designed, and the method is verified on the circuit. The test results prove the effectiveness of this method for generating high-resolution ADC test signals

High-precision state of charge estimation of urban-road-condition lithium-ion batteries based on optimized high-order term compensation-adaptive extended Kalman filtering.

It is significant to improve the accuracy of estimating the state of charge (SOC) of lithium-ion batteries under different working conditions on urban roads. In this study, an improved second-order polarized equivalent circuit (SO-PEC) modeling method is proposed. Accuracy test using segmented parallel exponential fitting parameter identification method. Online parameter identification using recursive least squares with variable forgetting factors(VFFRLS). An optimized higher-order term compensation-adaptive extended Kalman filter (HTC-AEKF) is proposed in the process of estimating SOC. The algorithm incorporates a noise-adaptive algorithm that introduces noise covariance into the recursive process in real-time to reduce the impact of process noise and observation noise on the accuracy of SOC estimation. Multiple iterations are performed for some of the processes in the extended Kalman filter(EKF) to compensate for the accuracy impact of missing higher-order terms in the linearization process. Model validation results show over 98% accuracy. The results after comparing with the EKF algorithm show a 4.1% improvement in SOC estimation accuracy under Hybrid Pulse Power Characterization(HPPC) working conditions. 2.7% improvement in accuracy in Dynamic Stress Test(DST) working conditions. 2.1% improvement in Beijing Bus Dynamic Stress Test(BBDST) working conditions. The superiority of the algorithm is demonstrated