An Integrated Critical Information Delivery Platform for Smart Segment Dissemination to Road Users

An integrated critical information delivery platform for smart segment dissemination to road users was developed. A statewide baseline milepost geodatabase was created at 0.1-mile resolution with tools, protocols, and interfaces that allow other data sources to be efficiently utilized. A variety of data sources (e.g., INRIX, CARS, Doppler, camera images, connected vehicle data, automated vehicle location) were integrated into existing and new dashboards for stakeholders to monitor roadway conditions and after-action reviews. Additionally, based on these data sources, algorithms were developed and an API was created to identify hazardous road conditions when the location of the end-user mobile device was given. Message delivery schemes were successfully implemented to issue alerts to drivers, which were integrated with two in-vehicle smartphone applications. The performance of the integrated platform was evaluated using both the driving simulator and a number of simulated and on-road tests. The results demonstrated the system was able to disseminate data in real-time using the developed platform

Anti-Tumor Drug Discovery Based on Natural Product β-Elemene: Anti-Tumor Mechanisms and Structural Modification

Natural products are important sources for drug discovery, especially anti-tumor drugs. β-Elemene, the prominent active ingredient extract from the rhizome of Curcuma wenyujin, is a representative natural product with broad anti-tumor activities. The main molecular mechanism of β-elemene is to inhibit tumor growth and proliferation, induce apoptosis, inhibit tumor cell invasion and metastasis, enhance the sensitivity of chemoradiotherapy, regulate the immune system, and reverse multidrug resistance (MDR). Elemene oral emulsion and elemene injection were approved by the China Food and Drug Administration (CFDA) for the treatment of various cancers and bone metastasis in 1994. However, the lipophilicity and low bioavailability limit its application. To discover better β-elemene-derived anti-tumor drugs with satisfying drug-like properties, researchers have modified its structure under the premise of not damaging the basic scaffold structure. In this review, we comprehensively discuss and summarize the potential anti-tumor mechanisms and the progress of structural modifications of β-elemene

Occurrence and distribution of neonicotinoid insecticides in surface water and sediment of the Guangzhou section of the Pearl River, South China

Little information is available about the occurrence of neonicotinoid insecticides in surface water and sediment of the metropolitan regions around the rivers in China. Here we investigate the residual level of neonicotinoids in the Guangzhou section of the Pearl River. At least one or two neonicotinoids was detected in each surface water and sediment, and the total amount of neonicotinoids (Sigma(5)neonics) in surface water ranged from 92.6 to 321 ng/L with a geometric mean (GM) of 174 ng/L. Imidacloprid, thiamethoxam and acetamiprid were three frequently detected neonicotinoids (100%2 from surface water. As for the sediment, total concentration was varied between 0.40 and 2.59 ng/g dw with a GM of 1.12 ng/g dw, and acetamiprid and thiacloprid were the common sediment neonicotinoids. Western and Front river-route of the Guangzhou section of the Pearl River suffered a higher neonicotinoids contamination than the Rear river-route, resulting from more effluents of WWTP5 receiving, and intensive commercial and human activities. Level of residual neonicotinoids in surface water was significantly correlated with the water quality (p < 0.01), especially items of pH, DO and ORP, and nitrogen and phosphorus contaminants. Compared with reports about residual neonicotinoids in water and sediment previously, the metropolitan regions of the Guangzhou could be confronted with a moderate contamination and showed serious ecological threats (even heavier than the Pearl Rivers). Our results will provide valuable data for understanding of neonicotinoids contamination in the Pearl River Delta and be helpful for further assessing environmental risk of neonicotinoids. (C) 2019 Elsevier Ltd. All rights reserved

Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from β-elemene scaffold

Abstractβ-Elemene is the major active ingredient of TCM anticancer drug elemene extracts. To further improve its antitumor activity and poor solubility, a polar HDACi pharmacophore was incorporated its scaffold. Systematic SAR studies led to the discovery of compounds 27f and 39f, which exhibited potent inhibitory activity against HDACs (HDAC1: IC50 = 22 and 9 nM; HDAC6: 8 and 14 nM, respectively). In cellular levels, 27f and 39f significantly inhibited cell proliferation of five tumour cell lines (IC50: 0.79 - 4.42 µM). Preliminary mechanistic studies indicated that 27f and 39f efficiently induced cell apoptosis. Unexpectedly, compound 39f could also stimulate cell cycle arrest in G1 phase. Further in vivo study in WSU-DLCL-2 xenografted mouse model validated the antitumor activities of 27f, without significant toxicity. The results suggest the therapeutic potential of these HDACs inhibitors in lymphoma and provide valuable insight and understanding for further structural optimisation around β-elemene scaffold

Recent Advances in Synergistic Antitumor Effects Exploited from the Inhibition of Ataxia Telangiectasia and RAD3-Related Protein Kinase (ATR)

As one of the key phosphatidylinositol 3-kinase-related kinases (PIKKs) family members, ataxia telangiectasia and RAD3-related protein kinase (ATR) is crucial in maintaining mammalian cell genomic integrity in DNA damage response (DDR) and repair pathways. Dysregulation of ATR has been found across different cancer types. In recent years, the inhibition of ATR has been proven to be effective in cancer therapy in preclinical and clinical studies. Importantly, tumor-specific alterations such as ATM loss and Cyclin E1 (CCNE1) amplification are more sensitive to ATR inhibition and are being exploited in synthetic lethality (SL) strategy. Besides SL, synergistic anticancer effects involving ATRi have been reported in an increasing number in recent years. This review focuses on the recent advances in different forms of synergistic antitumor effects, summarizes the pharmacological benefits and ongoing clinical trials behind the biological mechanism, and provides perspectives for future challenges and opportunities. The hope is to draw awareness to the community that targeting ATR should have great potential in developing effective anticancer medicines

Multicolor Barcoding in a Single Upconversion Crystal

We report the synthesis of luminescent crystals based on hexagonal-phase NaYF₄ upconversion microrods. The synthetic procedure involves an epitaxial end-on growth of upconversion nanocrystals comprising different lanthanide activators onto the NaYF₄ microrods. This bottom-up method readily affords multicolor-banded crystals in gram quantity by varying the composition of the activators. Importantly, the end-on growth method using one-dimensional microrods as the template enables facile multicolor tuning in a single crystal, which is inaccessible in conventional upconversion nanoparticles. We demonstrate that these novel materials offer opportunities as optical barcodes for anticounterfeiting and multiplexed labeling applications

Multicolor Barcoding in a Single Upconversion Crystal

We report the synthesis of luminescent crystals based on hexagonal-phase NaYF₄ upconversion microrods. The synthetic procedure involves an epitaxial end-on growth of upconversion nanocrystals comprising different lanthanide activators onto the NaYF₄ microrods. This bottom-up method readily affords multicolor-banded crystals in gram quantity by varying the composition of the activators. Importantly, the end-on growth method using one-dimensional microrods as the template enables facile multicolor tuning in a single crystal, which is inaccessible in conventional upconversion nanoparticles. We demonstrate that these novel materials offer opportunities as optical barcodes for anticounterfeiting and multiplexed labeling applications

Optimization of Structure and Electrical Characteristics for Four-Layer Vertically-Stacked Horizontal Gate-All-Around Si Nanosheets Devices

In this paper, the optimizations of vertically-stacked horizontal gate-all-around (GAA) Si nanosheet (NS) transistors on bulk Si substrate are systemically investigated. The release process of NS channels was firstly optimized to achieve uniform device structures. An over 100:1 selective wet-etch ratio of GeSi to Si layer was achieved for GeSi/Si stacks samples with different GeSi thickness (5 nm, 10 nm, and 20 nm) or annealing temperatures (≤900 °C). Furthermore, the influence of ground-plane (GP) doping in Si sub-fin region to improve electrical characteristics of devices was carefully investigated by experiment and simulations. The subthreshold characteristics of n-type devices were greatly improved with the increase of GP doping doses. However, the p-type devices initially were improved and then deteriorated with the increase of GP doping doses, and they demonstrated the best electrical characteristics with the GP doping concentrations of about 1 × 1018 cm−3, which was also confirmed by technical computer aided design (TCAD) simulation results. Finally, 4 stacked GAA Si NS channels with 6 nm in thickness and 30 nm in width were firstly fabricated on bulk substrate, and the performance of the stacked GAA Si NS devices achieved a larger ION/IOFF ratio (3.15 × 105) and smaller values of Subthreshold swings (SSs) (71.2 (N)/78.7 (P) mV/dec) and drain-induced barrier lowering (DIBLs) (9 (N)/22 (P) mV/V) by the optimization of suppression of parasitic channels and device’s structure