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Hundreds of neurotoxic insecticides are currently in use. However, only a few direct targets have been identified. Here, using Drosophila and the insecticide flonicamid, we identified nicotinamidase (Naam) as a previous unidentified molecular target for an insecticide. Naam is expressed in chordotonal stretch-receptor neurons, and inhibition of Naam by a metabolite of flonicamid, TFNA-AM (4-trifluoromethylnicotinamide), induces accumulation of substrate nicotinamide and greatly inhibits negative geotaxis. Engineered flies harboring a point mutation in the active site show insecticide resistance and defects in gravity sensing. Bees are resistant to flonicamid because of a gene duplication, resulting in the generation of a TFNA-AM-insensitive Naam. Our results, in combination with the absence of genes encoding Naam in vertebrate genomes, suggest that TFNA-AM and potential species-specific Naam inhibitors could be developed as novel insecticides, anthelmintics, and antimicrobials for agriculture and human health.

The international standards IEEE 1474 and IEC 62290 for fully automatic operation (FAO) systems in urban rail transit were respectively set by IEEE-SA (institute of electrical and electronics engineers-standard association) and IEC (international electrotechnical commission) in 1999 and 2004. These two standards are different but related. In this paper, the working progress, relevance, the driverless definition, application scope, architecture, functional requirements and focus issues of IEC 62290 and IEEE 1474 are compared and analyzed respectively. IEEE 1474 is the theoretical foundation for research and development personnel in the field of railway signaling, which is applicable to operation control systems of urban rail transit, trunk railways and medium to high speed maglev, and IEC 62290 is more suitable for FAO systems in urban rail transit.

This study proposed an innovative automated approach to differentiation of the vocabulary proficiency of Chinese speakers. A robust K-means algorithm was designed to compare the oral proficiency between L1 and L2 Chinese speakers regarding lexical richness and how relatively effective the various lexical measures were in performing the differentiation task. Eighteen lexical richness measures were surveyed and compared using the clustering analysis. The effectiveness of each selected measure as well as an overall evaluation of all the measures for the concerned differentiation tasks were comprehensively calibrated. The results demonstrate that, while the L1 versus L2 group difference in lexical richness was observed with statistical significance for each of the chosen measures, the clustering and membership prediction accuracy of individual speakers varied greatly from one measure to another. The implication is that a more fully defined metric of lexical richness is still a worthwhile endeavor for language proficiency assessment, with optimal directions for such endeavors discussed in the concluding remarks.

While the public sector is traditionally the sole provider for much of infrastructure, the pendulum is shifting in light of the enormous investment gap. Across the Global South, public utilities and planning agencies are engaging with the private sector to help bridge the gap. What are the key patterns of private participation in infrastructure (PPI) across countries in the Global South? What macro factors underscore such private participation? These research questions motivate this paper, focusing on five infrastructure sectors across the Global South and its regions. Following a historical synthesis of the changing balance of public and private provision, the paper outlines recent patterns of PPI. Drawing from a World Bank database, a regression analysis includes key macro-level predictors for private sector financing, for both the number of projects and stock of investment. Key results point to the importance of market size and in turn the potential for risk diversification, as well as a set of governance factors underlining investor confidence and stable environment. [ABSTRACT FROM AUTHOR]

Recognizing the importance of incorporating different risk measures in the portfolio management model, this paper examines the dynamic mean-risk portfolio optimization problem using both variance and value at risk (VaR) as risk measures. By employing the martingale approach and integrating the quantile optimization technique, we provide a solution framework for this problem. We demonstrate that, under a general market setting, the optimal terminal wealth may exhibit different patterns. When the market parameters are deterministic, we derive the closed-form solution for this problem. Examples are provided to illustrate the solution procedure of our method and demonstrate the benefits of our dynamic portfolio model compared to its static counterpart. [ABSTRACT FROM AUTHOR]

Simple Summary: Insects have special receptors called RDL that regulate the effects of a neurotransmitter GABA in their nervous system. Interestingly, these receptors are also the main targets of many insecticides used to control pests. We used fruit flies with different variants of the Rdl gene and tested four new types of meta-diamide and isoxazoline insecticides. The results showed that some mutations made the flies less sensitive to certain insecticides, while another mutation made the flies super resistant to all of the insecticides tested. Using computer simulations, we explored how these mutations might be affecting the insecticides' ability to attach. We found that specific areas between parts of the receptor seem to be important for these new insecticides to work. This helps us understand how insects can resist these insecticides and might lead to better ways to control pests in the future. Ionotropic γ-aminobutyric acid (GABA) receptors in insects, specifically those composed of the RDL (resistant to dieldrin) subunit, serve as important targets for commonly used synthetic insecticides. These insecticides belong to various chemical classes, such as phenylpyrazoles, cyclodienes, meta-diamides, and isoxazolines, with the latter two potentially binding to the transmembrane inter-subunit pocket. However, the specific amino acid residues that contribute to the high sensitivity of insect RDL receptors to these novel insecticides remain elusive. In this study, we investigated the susceptibility of seven distinct Drosophila melanogaster Rdl point mutants against four meta-diamide and isoxazoline insecticides: isocycloseram, fluxametamide, fluralaner, and broflanilide. Our findings indicate that, despite exhibiting increased sensitivity to fluralaner in vitro, the RdlI276C mutant showed resistance to isocycloseram and fluxametamide. Similarly, the double-points mutant RdlI276F+G279S also showed decreased sensitivity to the tested isoxazolines. On the other hand, the RdlG335M mutant displayed high levels of resistance to all tested insecticides. Molecular modeling and docking simulations further supported these findings, highlighting similar binding poses for these insecticides. In summary, our research provides robust in vivo evidence supporting the idea that the inter-subunit amino acids within transmembrane M1 and M3 domains form the binding site crucial for meta-diamide and isoxazoline insecticide interactions. This study highlights the complex interplay between mutations and insecticide susceptibility, paving the way for more targeted pest control strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Cystic echinococcosis (CE) is a human and animal health problem in many endemic areas worldwide. It is considered a neglected zoonotic disease caused by the larval form (hydatid cyst) of Echinococcus spp. tapeworm. There are limited studies on echinococcosis in Pakistan. Methods A cross-sectional survey was conducted to find out recent knowledge, attitudes and practices on the occurrence of cystic echinococcosis in butchers and dog owners in both urban and rural areas of Rawalpindi/Islamabad regions, Pakistan. The quantitative data was collected in the form of questionnaires to investigate the knowledge and awareness of CE among community members and their routine practices that were behind the factors involved in hydatid cyst infection. The practices and infrastructure of abattoirs/butcher shops and their role in transmission of cystic echinococcosis were also evaluated in the present study. Results The participants involved in the study were dog owners and people who kept animals. A total of 400 people were interviewed and 289 questionnaires were received. The results showed that only 4.1% of people have heard about the disease, and 58.1% were closely associated with dogs. Sixty-three percent of dogs in study area were consuming uncooked organs (e.g. liver, lung, etc.) of slaughtered animals, while 100% of dogs at butcher shops were consuming uncooked organs. Home slaughtering was common in 20.06%. Among butchers, 32.3% had heard about zoonoses and 7.61% knew about CE. The statistical analysis showed that there was highly significant difference (P < 0.05) among most of the practices that were associated with the prevalence of CE. Conclusions It was concluded from the present study that, the knowledge and awareness of CE among people of Rawalpindi/Islamabad were low. Because of dogs and poor knowledge of CE among community members and butchers, the transmission of echinococcosis is facilitated. Therefore, there is urgent need to strengthen awareness and health education among people, as well as proper practices related to the CE not only in the study area, but also in other areas of Pakistan.

Silver-based chalcogenide semiconductors exhibit low toxicity and near-infrared optical properties and are therefore extensively employed in the field of solar cells, photodetectors, and biological probes. Here, we report a facile mixture precursor hot-injection colloidal route to prepare Ag2TexS1−x ternary quantum dots (QDs) with tunable photoluminescence (PL) emissions from 950 nm to 1600 nm via alloying band gap engineering. As a proof-of-concept application, the Ag2TexS1−x QDs-based near-infrared photodetector (PD) was fabricated via solution-processes to explore their photoelectric properties. The ICP-OES results reveal the relationship between the compositions of the precursor and the samples, which is consistent with Vegard's equation. Alloying broadened the absorption spectrum and narrowed the band gap of the Ag2S QDs. The UPS results demonstrate the energy band alignment of the Ag2Te0.53S0.47 QDs. The solution-processed Ag2TexS1−x QD-based PD exhibited a photoresponse to 1350 nm illumination. With an applied voltage of 0.5 V, the specific detectivity is 0.91 × 1010 Jones and the responsivity is 0.48 mA/W. The PD maintained a stable response under multiple optical switching cycles, with a rise time of 2.11 s and a fall time of 1.04 s, which indicate excellent optoelectronic performance. [ABSTRACT FROM AUTHOR]