Digital Data Storage Using DNA Nanostructures and Solid-State Nanopores.

Solid-state nanopores are powerful tools for reading the three-dimensional shape of molecules, allowing for the translation of molecular structure information into electric signals. Here, we show a high-resolution integrated nanopore system for identifying DNA nanostructures that has the capability of distinguishing attached short DNA hairpins with only a stem length difference of 8 bp along a DNA double strand named the DNA carrier. Using our platform, we can read up to 112 DNA hairpins with a separating distance of 114 bp attached on a DNA carrier that carries digital information. Our encoding strategy allows for the creation of a library of molecules with a size of up to 5 × 1033 (2112) that is only built from a few hundred types of base molecules for data storage and has the potential to be extended by linking multiple DNA carriers. Our platform provides a nanopore- and DNA nanostructure-based data storage method with convenient access and the potential for miniature-scale integration

Dynamic prediction of traffic incident duration on urban expressways: a deep learning approach based on LSTM and MLP

Purpose – Efficient traffic incident management is needed to alleviate the negative impact of traffic incidents. Accurate and reliable estimation of traffic incident duration is of great importance for traffic incident management. Previous studies have proposed models for traffic incident duration prediction; however, most of these studies focus on the total duration and could not update prediction results in real-time. From a traveler’s perspective, the relevant factor is the residual duration of the impact of the traffic incident. Besides, few (if any) studies have used dynamic traffic flow parameters in the prediction models. This paper aims to propose a framework to fill these gaps. Design/methodology/approach – This paper proposes a framework based on the multi-layer perception (MLP) and long short-term memory (LSTM) model. The proposed methodology integrates traffic incident-related factors and real-time traffic flow parameters to predict the residual traffic incident duration. To validate the effectiveness of the framework, traffic incident data and traffic flow data from Shanghai Zhonghuan Expressway are used for modeling training and testing. Findings – Results show that the model with 30-min time window and taking both traffic volume and speed as inputs performed best. The area under the curve values exceed 0.85 and the prediction accuracies exceed 0.75. These indicators demonstrated that the model is appropriate for this study context. The model provides new insights into traffic incident duration prediction. Research limitations/implications – The incident samples applied by this study might not be enough and the variables are not abundant. The number of injuries and casualties, more detailed description of the incident location and other variables are expected to be used to characterize the traffic incident comprehensively. The framework needs to be further validated through a sufficiently large number of variables and locations. Practical implications – The framework can help reduce the impacts of incidents on the safety of efficiency of road traffic once implemented in intelligent transport system and traffic management systems in future practical applications. Originality/value – This study uses two artificial neural network methods, MLP and LSTM, to establish a framework aiming at providing accurate and time-efficient information on traffic incident duration in the future for transportation operators and travelers. This study will contribute to the deployment of emergency management and urban traffic navigation planning

Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force

IntroductionAntimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections.MethodsWe verified that exogenous L-arginine promoted the killing effect of gentamicin against Salmonella in vitro and in vivo, and measured intracellular ATP, NADH, and PMF of bacteria. Gene expression was determined using real-time quantitative PCR.ResultsThis study found that alkaline arginine significantly increased gentamicin, tobramycin, kanamycin, and apramycin-mediated killing of drug-resistant Salmonella, including multidrug-resistant strains. Mechanistic studies showed that exogenous arginine was shown to increase the proton motive force, increasing the uptake of gentamicin and ultimately inducing bacterial cell death. Furthermore, in mouse infection model, arginine effectively improved gentamicin activity against Salmonella typhimurium.DiscussionThese findings confirm that arginine is a highly effective and harmless aminoglycoside adjuvant and provide important evidence for its use in combination with antimicrobial agents to treat drug-resistant bacterial infections

A Novel Systems Pharmacology Method to Investigate Molecular Mechanisms of Scutellaria barbata D. Don for Non-small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, cytotoxic chemotherapy, surgical resection, radiation, and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC is relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is imperative to identify or develop efficient lead compounds for the treatment of NSCLC. Here, we report that the herb Scutellaria barbata D. Don (SBD) can effectively treat NSCLC by anti-inflammatory, promoting apoptosis, cell cycle arrest, and angiogenesis. In this work, we analyze the molecular mechanism of SBD for NSCLC treatment by applying the systems pharmacology strategy. This method combines pharmacokinetics analysis with pharmacodynamics evaluation to screen out the active compounds, predict the targets and assess the networks and pathways. Results show that 33 compounds were identified with potential anti-cancer effects. Utilizing these active compounds as probes, we predicted that 145 NSCLC related targets mainly involved four aspects: apoptosis, inflammation, cell cycle, and angiogenesis. And in vitro experiments were managed to evaluate the reliability of some vital active compounds and targets. Overall, a complete overview of the integrated systems pharmacology method provides a precise probe to elucidate the molecular mechanisms of SBD for NSCLC. Moreover, baicalein from SBD effectively inhibited tumor growth in an LLC tumor-bearing mice models, demonstrating the anti-tumor effects of SBD. Our findings further provided experimental evidence for the application in the treatment of NSCLC

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

Inhibition of vitamin D analog eldecalcitol on hepatoma in vitro and in vivo

Hepatoma is a serious liver cancer with high morbidity and mortality. Eldecalcitol (ED-71), a vitamin D analog, is extensively used as anti-cancer agent in vitro. Hepatocellular carcinoma cell, SMMC-7721 cell lines were used in this study. Transwell assay, cell apoptosis and cell cycle detection assays were investigated after treatment with ED-71 and phosphate buffered saline (PBS) as control. Sizes of tumors were measured after ED-71 treatment in a mouse model. E-cadherin and Akt gene expressions were detected by real-time PCR (RT-PCR). The results showed that cell invasion and migration were decreased markedly after ED-71 treatment compared to control group. Cell cycle detection showed that the G2 stage was 13.18% and total S-stage was 41.16% in the ED-71 group and G2 stage: 22.88%, total S-stage: 27.34% in the control group. Cell apoptosis rate was promoted in the ED-71 group. Size of the tumors reduced more after the ED-71 treatment than the PBS treatment in mice. ED-71 markedly inhibited the expression of Akt and E-cadherin, either detected by immunohistochemistry or RT-PCR. ED-71 treatment can inhibit the hepatoma agent proliferation by increasing the E-cadherin expression and decreasing Akt expression. Therefore, these findings provide novel evidence that ED-71 can be used as an anti-hepatoma agent

Using vanishing points to estimate parameters of fisheye camera

This study presents an approach for estimating the fisheye camera parameters using three vanishing points corresponding to three sets of mutually orthogonal parallel lines in one single image. The authors first derive three constraint equations on the elements of the rotation matrix in proportion to the coordinates of the vanishing points. From these constraints, the rotation matrix is calculated under the assumption of the image centre known. The experimental results with synthetic images and real fisheye images validate this method. In contrast to the existing methods, the authors method needs less image information and does not know the three‐dimensional reference point coordinates