Molecular mechanism of de novo replication by the Ebola virus polymerase.

Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory infections, haemorrhagic fever and encephalitis in humans and animals, and are considered a substantial health and economic burden worldwide1. Replication and transcription of the viral genome are executed by the large (L) polymerase, which is a promising target for the development of antiviral drugs. Here, using the L polymerase of EBOV as a representative, we show that de novo replication of L polymerase is controlled by the specific 3' leader sequence of the EBOV genome in an enzymatic assay, and that formation of at least three base pairs can effectively drive the elongation process of RNA synthesis independent of the specific RNA sequence. We present the high-resolution structures of the EBOV L-VP35-RNA complex and show that the 3' leader RNA binds in the template entry channel with a distinctive stable bend conformation. Using mutagenesis assays, we confirm that the bend conformation of the RNA is required for the de novo replication activity and reveal the key residues of the L protein that stabilize the RNA conformation. These findings provide a new mechanistic understanding of RNA synthesis for polymerases of non-segmented negative-strand RNA viruses, and reveal important targets for the development of antiviral drugs.

The Joint Adaptive Kalman Filter (JAKF) for Vehicle Motion State Estimation.

This paper proposes a multi-sensory Joint Adaptive Kalman Filter (JAKF) through extending innovation-based adaptive estimation (IAE) to estimate the motion state of the moving vehicles ahead. JAKF views Lidar and Radar data as the source of the local filters, which aims to adaptively adjust the measurement noise variance-covariance (V-C) matrix 'R' and the system noise V-C matrix 'Q'. Then, the global filter uses R to calculate the information allocation factor 'ß' for data fusion. Finally, the global filter completes optimal data fusion and feeds back to the local filters to improve the measurement accuracy of the local filters. Extensive simulation and experimental results show that the JAKF has better adaptive ability and fault tolerance. JAKF enables one to bridge the gap of the accuracy difference of various sensors to improve the integral filtering effectivity. If any sensor breaks down, the filtered results of JAKF still can maintain a stable convergence rate. Moreover, the JAKF outperforms the conventional Kalman filter (CKF) and the innovation-based adaptive Kalman filter (IAKF) with respect to the accuracy of displacement, velocity, and acceleration, respectively.

Risk finance for catastrophe losses with Pareto-calibrated Lévy-stable severities.

For catastrophe losses, the conventional risk finance paradigm of enterprise risk management identifies transfer, as opposed to pooling or avoidance, as the preferred solution. However, this analysis does not necessarily account for differences between light- and heavy-tailed characteristics of loss portfolios. Of particular concern are the decreasing benefits of diversification (through pooling) as the tails of severity distributions become heavier. In the present article, we study a loss portfolio characterized by nonstochastic frequency and a class of Lévy-stable severity distributions calibrated to match the parameters of the Pareto II distribution. We then propose a conservative risk finance paradigm that can be used to prepare the firm for worst-case scenarios with regard to both (1) the firm's intrinsic sensitivity to risk and (2) the heaviness of the severity's tail.

Immunomodulatory effects of selenium-enriched peptides from soybean in cyclophosphamide-induced immunosuppressed mice.

In this study, selenium-enriched soybean peptides (<3 kDa, named Se-SPep) was isolated and purified from the selenium-enriched soybean protein (Se-SPro) hydrolysate by ultrafiltration. The in-vivo immunomodulatory effects of Se-SPep were investigated in cyclophosphamide-induced immunosuppressed mice. Se-SPep treatment could alleviate the atrophy of immune organs and weight loss observed in immunosuppressive mice. Besides, Se-SPep administration could dramatically improve total protein, albumin, white blood cell, immunoglobulin (Ig) M, IgG, and IgA levels in blood. Moreover, Se-SPep strongly stimulated interleukin-2 (IL-2), interferon-gamma (IFN-γ), nitric oxide (NO), and cyclic guanosine monophosphate productions by up-regulating mRNA expressions of IL-2, IFN-γ, and inducible NO synthase in spleen tissue. Furthermore, Se-SPep exhibits more effective immunomodulatory activity compared to Se-SPro and SPep. In conclusion, Se-SPep could effectively enhance the immune capacity of immunosuppressive mice. These findings confirm Se-SPep is an effective immunomodulator with potential application in functional foods or dietary supplements.

Occurrence and Characterization of Salmonella Isolated from Large-Scale Breeder Farms in Shandong Province, China.

This study aimed to investigate the prevalence and antimicrobial resistance of Salmonella spp. isolated from large-scale breeder farms in Shandong Province, China. A total of 63 Salmonella isolates (63/409, 15.4%) were identified from 409 samples collected from five large-scale breeder farms in Shandong Province. These Salmonella isolates were assayed for serotype, antimicrobial susceptibility, prevalence of class 1 integrons, quinolone resistance genes, and ß-lactamase genes and subtyped by multilocus sequence typing (MLST). Among these isolates, S. Enteritidis (100%) was the predominant serovar, and high antimicrobial resistance rates to nalidixic acid (100.0%), streptomycin (100.0%), ampicillin (98.4%), and erythromycin (93.7%) were observed. All of the isolates carried blaTEM. MLST results showed that only one sequence type (ST11) was identified. Our findings indicated that Salmonella was generally prevalent not only on broiler farms but also on breeder farms.