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LEDs are widely used for both general and automotive lighting since their brightness can be easily regulated by controlling their on/off time using methods such as pulse width modulation (PWM). However, lighting control using PWM can cause temporal light artefacts, such as the phantom array effect, which affect human visual perception. In this study, we determined the influence of different colour temperatures on the visibility of the phantom array effect using five LEDs with different spectral distributions (red, green, blue, warm white and cool white) and frequencies of temporal modulation ranging from 1 kHz to 11 kHz. The threshold of the warm white LED was between that of the green and red LEDs, and threshold of the cool white LED was between that of the red and blue LEDs. The experimental results revealed a difference in the threshold frequency of the visibility of the phantom array effect, in accordance with the spectral distribution and the colour temperature of the light source.

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5′-monophosphate–mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid–sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5′-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite Plasmodium falciparum , namely tyrosine RS ( Pf YRS). ML901 exerts whole-life-cycle–killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901.

Development of antimalarial compounds into clinical candidates remains costly and arduous without detailed knowledge of the target. As resistance increases and treatment options at various stages of disease are limited, it is critical to identify multistage drug targets that are readily interrogated in biochemical assays. Whole-genome sequencing of 18 parasite clones evolved using thienopyrimidine compounds with submicromolar, rapid-killing, pan–life cycle antiparasitic activity showed that all had acquired mutations in the P. falciparum cytoplasmic isoleucyl tRNA synthetase (cIRS). Engineering two of the mutations into drug-naïve parasites recapitulated the resistance phenotype, and parasites with conditional knockdowns of cIRS became hypersensitive to two thienopyrimidines. Purified recombinant P. vivax cIRS inhibition, cross-resistance, and biochemical assays indicated a noncompetitive, allosteric binding site that is distinct from that of known cIRS inhibitors mupirocin and reveromycin A. Our data show that Plasmodium cIRS is an important chemically and genetically validated target for next-generation medicines for malaria.

Given the great advancements in soft computing and data science, artificial neural network (ANN) has been explored and applied to handle complicated problems in the field of pavement engineering. This study conducted a state-of-the-art review for surveying the recent progress of ANN application at different stages of pavement engineering, including pavement design, construction, inspection and monitoring, and maintenance. This study focused on the papers published over the last three decades, especially the studies conducted since 2013. Through literature retrieval, a total of 683 papers in this field were identified, among which 143 papers were selected for an in-depth review. The ANN architectures used in these studies mainly included multi-layer perceptron neural network (MLPNN), convolutional neural network (CNN) and recurrent neural network (RNN) for processing one-dimensional data, two-dimensional data and time-series data. CNN-based pavement health inspection and monitoring attracted the largest research interest due to its potential to replace human labor. While ANN has been proved to be an effective tool for pavement material design, cost analysis, defect detection and maintenance planning, it is facing huge challenges in terms of data collection, parameter optimization, model transferability and low-cost data annotation. More attention should be paid to bring multidisciplinary techniques into pavement engineering to tackle existing challenges and widen future opportunities.

Emerging artemisinin resistance in Plasmodium falciparum malaria has the potential to become a global public health crisis. In Southeast Asia, this phenomenon clinically manifests in the form of delayed parasite clearance following artemisinin treatment. Reduced artemisinin susceptibility is limited to the early ring stage window, which is sufficient to allow parasites to survive the short half-life of artemisinin exposure. A screen of known clinically-implemented antimalarial drugs was performed to identify a drug capable of enhancing the killing activity of artemisinins during this critical resistance window. As a result, lumefantrine was found to increase the killing activity of artemisinin against an artemisinin-resistant clinical isolate harboring the C580Y kelch13 mutation. Isobologram analysis revealed synergism during the early ring stage resistance window, when lumefantrine was combined with artemether, an artemisinin derivative clinically partnered with lumefantrine. These findings suggest that lumefantrine should be clinically explored as a partner drug in artemisinin-based combination therapies to control emerging artemisinin resistance., Graphical abstract Image 1, Highlights • Artemisinin booster compound screening targeting the early ring resistance window in Plasmodium falciparum was performed. • Lumefantrine improves the activity of artesunate against the parasite during the resistance window. • Artemether and lumefantrine are synergistic during the early ring stage resistance window.