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Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the application of machine learning (ML) to whole-genome sequences (WGSs) has facilitated pathogen identification. However, relying solely on genetic information to identify emerging or new pathogens is fundamentally constrained, especially if novel virulence factors exist. In addition, even WGSs with ML pipelines are unable to discern phenotypes associated with cryptic genetic loci linked to virulence. Here, we set out to determine if ML using phenotypic hallmarks of pathogenesis could assess potential pathogenic threat without using any sequence-based analysis. This approach successfully classified potential pathogenetic threat associated with previously machine-observed and unobserved bacteria with 99% and 85% accuracy, respectively. This work establishes a phenotype-based pipeline for potential pathogenic threat assessment, which we term PathEngine, and offers strategies for the identification of bacterial pathogens.

Acetogenic bacteria can fix single-carbon (C 1 ) molecules. However, improvements are needed to overcome poor product titers. Butyribacterium methylotrophicum can naturally ferment C 1 compounds into longer-chained molecules such as butyrate alongside traditional acetate.

Using the Wood-Ljungdahl pathway, acetogens can nonphotosynthetically fix gaseous C(1) molecules, preventing them from entering the atmosphere. Many acetogens can also grow on liquid C(1) compounds such as formate and methanol, which avoid the storage and mass transfer issues associated with gaseous C(1) compounds. Substrate redox state also plays an important role in acetogen metabolism and can modulate products formed by these organisms. Butyribacterium methylotrophicum is an acetogen known for its ability to synthesize longer-chained molecules such as butyrate and butanol, which have significantly higher values than acetate or ethanol, from one-carbon (C(1)) compounds. We explored B. methylotrophicum’s C(1) metabolism by varying substrates, substrate concentrations, and substrate feeding strategies to improve four-carbon product titers. Our results showed that formate utilization by B. methylotrophicum favored acetate production and methanol utilization favored butyrate production. Cofeeding of both substrates produced a high butyrate titer of 4 g/liter when methanol was supplied in excess to formate. Testing of formate feeding strategies, in the presence of methanol, led to further increases in the butyrate to acetate ratio. Mixotrophic growth of liquid and gaseous C(1) substrates expanded the B. methylotrophicum product profile, as ethanol, butanol, and lactate were produced under these conditions. We also showed that B. methylotrophicum is capable of producing caproate, a six-carbon product, presumably through chain elongation cycles of the reverse β-oxidation pathway. Furthermore, we demonstrated butanol production via heterologous gene expression. Our results indicate that both selection of appropriate substrates and genetic engineering play important roles in determining titers of desired products. IMPORTANCE Acetogenic bacteria can fix single-carbon (C(1)) molecules. However, improvements are needed to overcome poor product titers. Butyribacterium methylotrophicum can naturally ferment C(1) compounds into longer-chained molecules such as butyrate alongside traditional acetate. Here, we show that B. methylotrophicum can effectively grow on formate and methanol to produce high titers of butyrate. We improved ratios of butyrate to acetate through adjusted formate feeding strategies and produced higher-value six-carbon molecules. We also expanded the B. methylotrophicum product profile with the addition of C(1) gases, as the organism produced ethanol, butanol, and lactate. Furthermore, we developed a transformation protocol for B. methylotrophicum to facilitate genetic engineering of this organism for the circular bioeconomy.

Sequencing technologies, in particular RNASeq, have become critical tools in the design, build, test and learn cycle of synthetic biology. They provide a better understanding of synthetic designs, and they help identify ways to improve and select designs. While these data are beneficial to design, their collection and analysis is a complex, multistep process that has implications on both discovery and reproducibility of experiments. Additionally, tool parameters, experimental metadata, normalization of data and standardization of file formats present challenges that are computationally intensive. This calls for high-throughput pipelines expressly designed to handle the combinatorial and longitudinal nature of synthetic biology. In this paper, we present a pipeline to maximize the analytical reproducibility of RNASeq for synthetic biologists. We also explore the impact of reproducibility on the validation of machine learning models. We present the design of a pipeline that combines traditional RNASeq data processing tools with structured metadata tracking to allow for the exploration of the combinatorial design in a high-throughput and reproducible manner. We then demonstrate utility via two different experiments: a control comparison experiment and a machine learning model experiment. The first experiment compares datasets collected from identical biological controls across multiple days for two different organisms. It shows that a reproducible experimental protocol for one organism does not guarantee reproducibility in another. The second experiment quantifies the differences in experimental runs from multiple perspectives. It shows that the lack of reproducibility from these different perspectives can place an upper bound on the validation of machine learning models trained on RNASeq data. Graphical Abstract

This research aims to investigate the relationship between ownership structure and dividend policy of Vietnamese listed companies. The empirical findings show that the government-controlled companies, the companies with high concentrated ownership and with recent right issue activities would have higher dividend payments. In addition, due to the change of Vietnamese dividend tax rate to encourage the market development after global economic crisis, we discover that when the personal income tax rate at higher level of 5%, the sate-owned firms in Ho Chi Minh Stock Exchange would still pay higher dividends, which represents the dividend preferences of the investors, the status of firms’ stable development and the effectiveness of national economic policies.

Understanding who is at risk of progression to severe coronavirus disease 2019 (COVID-19) is key to clinical decision making and effective treatment. We study correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ClinicalTrials.gov04545060). Laboratory parameters identify study participants at greater risk of severe disease, including a high neutrophil-to-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test, and whole-blood transcriptome profiles. Sotrovimab treatment is associated with normalization of NLR and the transcriptomic profile and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provides the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identify a 10-gene signature with similar predictive accuracy. We identify markers of risk for disease progression and demonstrate that normalization of these parameters occurs with antibody treatment of established infection.

Perfluorooctanoic acid (PFOA) is widespread in the environment, which causes serious health and safety concerns. A mechanistic study on reductive defluorination of PFOA by titanium(III) citrate in the presence of catalysts was conducted. Vitamin B12 was used to catalyze reduction reactions by shuttling electrons from a reducing agent (electron donor) to PFOA to produce a Co-carbon bond intermediates. In the presence of copper nanoparticles, a precursor complex, B12-C7F14COOH, adsorbed on the metal surface, followed by a hydrogenolytic reaction to form less-fluorinated products. The synergistic effect between vitamin B12 and copper nanoparticles enhances the reductive activities by electron-transfer reactions and hydrogenolysis. The efficient reduction of PFOA to less-noxious compounds was demonstrated with a copper dose of 2gL-1, titanium(III) citrate (45mM), and vitamin B12 (0.2mM) with an initial pH of 9.0 and 70°C. In this anoxic aqueous solution, the biomimetic reductive system effectively removed 65% of PFOA. The mass balance on fluoride matched the observed degradation of PFOA, while no short-chain intermediates were detected.

Globally, there is an expanding elderly population, and families are finding it increasingly challenging to coordinate care for their older family members. This paper reports on the usage patterns of InfoSAGE, an online private social network that has tools for communication and care coordination for elders and their families. This descriptive analysis describes the types of family networks using the platform and types of functionality most used by elders and their family members.

This study examines the relationship among information asymmetry, dividend policy and ownership structure for Chinese listed firms from 2003 to 2012. We find that firms with higher information asymmetry are less likely to pay dividends. Further, the sample is divided into state-controlled and non-state-controlled firms, and the results show that state-controlled firms with higher information asymmetry would pay higher dividends compared to non-state-controlled firms. In addition, we find that the split share structure reform enhanced information transparency, leading to a positive moderating effect on the relation between information asymmetry and dividend policy.

The design of a mobile medication manager within a broader family and elder-centric collaboration platform faces challenges of usability and wide applicability. To inform the development and use cases of eldercare apps, we present the preliminary results of a usability study of an iOS and Android app intended for both family members and aging adults for the mobile management of medication lists. Seven participants were recorded during the performance of eight typical use-case scenarios of the medication portion of the InfoSAGE app. Audio and video recordings were analyzed for themes and events. The aim of this paper is to help inform future design choices for eldercare mobile apps.

Understanding text often requires identifying meaningful constituent spans such as noun phrases and verb phrases. In this work, we show that we can effectively recover these types of labels using the learned phrase vectors from deep inside-outside recursive autoencoders (DIORA). Specifically, we cluster span representations to induce span labels. Additionally, we improve the model’s labeling accuracy by integrating latent code learning into the training procedure. We evaluate this approach empirically through unsupervised labeled constituency parsing. Our method outperforms ELMo and BERT on two versions of the Wall Street Journal (WSJ) dataset and is competitive to prior work that requires additional human annotations, improving over a previous state-of-the-art system that depends on ground-truth part-of-speech tags by 5 absolute F1 points (19% relative error reduction).

Single-crystalline Zn–ZnO core–shell nanofibers have been prepared by thermal evaporation of metallic Zn in an oxygen atmosphere. The diameter of the Zn core is 53 ± 1.0 nm while the thickness of the outer ZnO shell is 10 ± 1.5 nm, both are single crystalline and grow along the [ 1 1 2 ¯ 0 ] direction. Post-growth annealing leads to sublimation and out-diffusion of the Zn core that result in the formation of polycrystalline ZnO nanotubes. Metal-semiconductor-metal photodiodes (PDs) are fabricated by depositing In and Ag interdigitated electrodes on Zn–ZnO core–shell nanofibers. PDs fabricated with In contacts exhibit a maximum responsivity of 2 A/W at 300 nm. In contrast, PDs fabricated with Ag contacts exhibit a maximum responsivity of 10 A/W at 300 nm and a much faster decay rate which has been attributed to the formation of a Schottky barrier between Ag and ZnO.

This study investigates the effect of banking system reform on the investment behavior of Chinese listed firms. We find that the politically-oriented investment problem for state-controlled listed companies is mitigated by the reform due to foreign participation in the management of Chinese banks. The problem of underinvestment in non-state-controlled listed companies also appears to be alleviated due to an increase of bank loans. We include leverage in our analysis and the main findings are robust. The results provide evidence that Chinese banking system reform has increased the efficiency of resource allocation, easing investment distortions in state-controlled listed companies and reducing financial constraints in non-state-controlled listed companies.

Homeobox genes encode transcription factors that regulate embryonic development programs including organogenesis, axis formation and limb development. Previously, we identified and cloned a mouse double homeobox gene, Duxbl, whose homeodomain exhibits the highest identity (67 %) to human DUX4, a candidate gene of facioscapulohumeral muscular dystrophy (FSHD). Duxbl proteins have been shown to be expressed in elongated myocytes and myotubes of trunk and limb muscles during embryogenesis. In this study, we found that Duxbl maintained low expression levels in various adult muscles. Duxbl proteins were induced to express in activated satellite cells and colocalized with MyoG, a myogenic differentiating marker. Furthermore, Duxbl proteins were not detected in quiescent satellite cells but detected in regenerated myocytes and colocalized with MyoD and MyoG following cardiotoxin-induced muscle injury. Ectopic Duxbl overexpressions in C2C12 myoblast cells promoted cell proliferation through mainly enhancing cyclin D1 and hyper-phosphorylated retinoblastoma protein but reducing p21 expression. However, Duxbl overexpression in C2C12 cells inhibited myogenic differentiation by decreasing MyoD downstream gene expressions, including M-cadherin, MyoG, p21 and cyclin D3 but not MyoD itself. Duxbl overexpressions also promoted cell proliferation but blocked MyoD-induced myogenic conversion in multipotent mesenchymal C3H10T1/2 cells. In addition, results of a luciferase reporter assay suggest that Duxbl negatively regulated MyoG promoter activity through the proximal two E boxes. In conclusion, these results indicate that Duxbl may play a crucial role in myogenesis and postnatal muscle regeneration by activating and proliferating satellite and myoblast cells.

ZnO nanowire UV sensors were fabricated by using focused ion beam micromachining and thermal oxidation of metallic zinc microstructures. A metallic zinc “micro-strip” was first deposited by thermal evaporation with the aid of a shadow mask on SiO2/Si substrate. A 3-μm wide “trench” was cut across the metallic strip by focused ion beam; the subsequent thermal oxidation at 450 °C results in the growth of single crystalline [110] ZnO nanowires across the trench. The ZnO nanowire sensor was completed by patterning silver ohmic contacts on the two ends of the metallic strip. Our photoluminescence (PL) spectroscopic studies show that the room temperature emission of the ZnO nanowire is due to the recombination of free exciton and free to bound transition, while at 10 K, the PL is dominated by the recombination of surface excitons. Irradiated at 300 nm, the rise time, decay time and normalized photoconductive gain of the ZnO sensor were determined to be 200 ms, 400 ms and 3 × 10−6 m2V−1, respectively. The fast sensor response is due to the high crystalline quality of the nanowire, which facilitates a rapid equilibrium of absorption and desorption of molecular oxygen on the surface.

A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was applied as a primary screen to evaluate a marine-derived actinomycete extract library and identify human class III HDAC (SIRT) inhibitors. Based on the bioassay-guided purification, a new compound designated as streptosetin A (1) was obtained from one of the active strains identified through the yeast assay. The gross structure of the new compound was elucidated from the 1D and 2D NMR data. The absolute stereostructure of 1 was determined based on X-ray crystal structure analysis and simulation of ECD spectra using time-dependent density functional theory (TD-DFT) calculations. This compound showed weak inhibitory activity against yeast Sir2p, and human SIRT1 and SIRT2.

This paper analyzes share repurchase programs, which are subject to specific legal restrictions in Taiwan, to determine whether the unique item repurchase price range conveys information regarding the degree of undervaluation and future prospects of a firm. We find that the price range conveys such information, not only about the past, but also the future. Companies with a higher upper bound of the repurchase price range experience better abnormal returns than do companies that do not. The lower bound of the price range does not efficiently convey the undervaluation effect, owing to the exemption clause in the announcement. Finally, the announced price range, in turn, conveys favorable information about the repurchasing firm and is a more powerful signal of future prospects than is the legal price range.

Monacolin K is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus. The monacolin K biosynthetic gene cluster, mokA-mokI, has been characterized in Monascus pilosus. The mokH gene encoding Zn(II)2Cys6 binuclear DNA binding protein is assumed to be an activator for monacolin K production. In this study, the mokH gene was cloned and driven by the glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter for overexpression in M. pilosus. The transformants containing an extra copy of the mokH gene were obtained and verified by PCR and Southern hybridization. The transcripts of mokH in the transformants were expressed significantly higher than those of the wild-type strain. The transformants were stably inherited through the next generation, as determined by observation of the enhanced green fluorescent protein (EGFP). The transformant T-mokH1 also showed a 1.7-fold higher production of monacolin K than the wild-type strain in a time course analysis. Analysis of the RT-PCR products demonstrated that the monacolin K biosynthetic genes in the transformant were expressed to a greater extent than those in the wild-type strain. These results indicated that mokH upregulated the transcription of monacolin K biosynthetic genes and increased monacolin K production.

Citrinin, a hepato-nephrotoxic compound to humans, can be produced by the food fermentation microorganisms Monascus spp. In this study, we investigated the distribution of mycotoxin citrinin biosynthesis genes in 18 Monascus strains. The results show that the acyl-transferase and keto-synthase domains of the pksCT gene encoding citrinin polyketide synthase were found in Monascus purpureus, Monascus kaoliang, and Monascus sanguineus. Furthermore, the ctnA gene, a major activator for citrinin biosynthesis, was found in M. purpureus and M. kaoliang, but was absent in M. sanguineus. The orf3 gene encoding oxygenase, located between pksCT and ctnA, was also present in M. purpureus and M. kaoliang. The pksCT gene was highly conserved in M. purpureus, M. kaoliang, and M. sanguineus, while the ctnA and orf3 genes were shown to be highly homologous in M. purpureus and M. kaoliang. In contrast, the PCR and Southern blot analyses suggest that pksCT, ctnA, and orf3 were absent or significantly different in Monascus pilosus, Monascus ruber, Monascus barkeri, Monascus floridanus, Monascus lunisporas, and Monascus pallens. A citrinin-producing phenotype was detected only in M. purpureus and M. kaoliang using high performance liquid chromatography (HPLC). These results clearly indicate that the highly conserved citrinin gene cluster in M. purpureus and M. kaoliang carry out citrinin biosynthesis. In addition, according to the phylogenetic subgroups established with the beta-tubulin gene, the citrinin gene cluster can group the species of Monascus.

A continuous investigation of secondary metabolites produced by the sponge-derived fungus, Gymnascella dankaliensis , has yielded a new polyketide tyrosine derivative, dankastatin C ( 3 ) and the known steroid, demethylincisterol A 3 ( 4 ), which was originally found from a Homaxinella marine sponge. The stereostructure of the new compound has been determined based on the analysis of 1D and 2D NMR data. Dankastatin C ( 3 ) showed potent cell growth inhibitory activity against the murine P388 cell line.