Viruses of the family Flaviviridae are important pathogens of humans and other animals and are currently classified into four genera. To better understand their diversity, evolutionary history, and genomic flexibility, we used transcriptome sequencing (RNA-seq) to search for the viruses related to the Flaviviridae in a range of potential invertebrate and vertebrate hosts. Accordingly, we recovered the full genomes of five segmented jingmenviruses and 12 distant relatives of the known Flaviviridae ("flavilike" viruses) from a range of arthropod species. Although these viruses are highly divergent, they share a similar genomic plan and common ancestry with the Flaviviridae in the NS3 and NS5 regions. Remarkably, although these viruses fill in major gaps in the phylogenetic diversity of the Flaviviridae, genomic comparisons reveal important changes in genome structure, genome size, and replication/gene regulation strategy during evolutionary history. In addition, the wide diversity of flavi-like viruses found in invertebrates, as well as their deep phylogenetic positions, suggests that they may represent the ancestral forms from which the vertebrate-infecting viruses evolved. For the vertebrate viruses, we expanded the previously mammal-only pegivirus-hepacivirus group to include a virus from the graceful catshark (Proscyllium habereri), which in turn implies that these viruses possess a larger host range than is currently known. In sum, our data show that the Flaviviridae infect a far wider range of hosts and exhibit greater diversity in genome structure than previously anticipated. IMPORTANCEThe family Flaviviridae of RNA viruses contains several notorious human pathogens, including dengue virus, West Nile virus, and hepatitis C virus. To date, however, our understanding of the biodiversity and evolution of the Flaviviridae has largely been directed toward vertebrate hosts and their blood-feeding arthropod vectors. Therefore, we investigated an expanded group of potential arthropod and vertebrate host species that have generally been ignored by surveillance programs. Remarkably, these species contained diverse flaviviruses and related viruses that are characterized by major changes in genome size and genome structure, such that these traits are more flexible than previously thought. More generally, these data suggest that arthropods may be the ultimate reservoir of the Flaviviridae and related viruses, harboring considerable genetic and phenotypic diversity. In sum, this study revises the traditional view on the evolutionary history, host range, and genomic structures of a major group of RNA viruses. Since the discovery of the virological cause of yellow fever in the 1920s, viruses of the family Flaviviridae have been well documented as the cause of major vector-borne and hepatic diseases in humans (1). The family as currently classified comprises four genera: Flavivirus, Hepacivirus, Pestivirus, and the newly proposed genus Pegivirus (2). Despite the extensive divergence between these viruses, they share...

This paper concerns the communication primitives of broadcasting (one-to-all communication) and gossiping (all-to-all communication) in radio networks with known topology, i.e., where for each primitive the schedule of transmissions is precomputed based on full knowledge about the size and the topology of the network.The first part of the paper examines the two communication primitives in general graphs. In particular, it proposes a new (efficiently computable) deterministic schedule that uses O(D + ∆ log n) time units to complete the gossiping task in any radio network with size n, diameter D and max-degree ∆. Our new schedule improves and simplifies the currently best known gossiping schedule, requiring time O(D + i+2 √ D∆ log i+1 n), for any network with the diameter D = Ω(log i+4 n), where i is an arbitrary integer constant i ≥ 0, see [17]. For the broadcast task we deliver two new results: a deterministic efficient algorithm for computing a radio schedule of length D + O(log 3 n), and a randomized algorithm for computing a radio schedule of length D + O(log 2 n). These results improve on the best currently known D + O(log 4 n) time schedule due to Elkin and Kortsarz [12].The second part of the paper focuses on radio communication in planar graphs, devising a new broadcasting schedule using fewer than 3D time slots. This result improves, for small values of D, on currently best known D + O(log 3 n) time schedule proposed by Elkin and Kortsarz in [12]. Our new algorithm should be also seen as the separation result between the planar and the general graphs with a small diameter due to the polylogarithmic inapproximability result in general graphs due to Elkin and Kortsarz, see [11].

This paper concerns the communication primitives of broadcasting (one-to-all communication) and gossiping (all-to-all communication) in radio networks with known topology, i.e., where for each primitive the schedule of transmissions is precomputed based on full knowledge about the size and the topology of the network.

Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-kB (NF-kB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocininduced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. The expression and function of P2X3Rs was markedly enhanced in hindpaw-innervated DRG neurons in diabetic rats. The CpG (cytosine guanine dinucleotide) island in the p2x3r gene promoter region was significantly demethylated, and the expression of DNA methyltransferase 3b was remarkably downregulated in DRGs in diabetic rats. The binding ability of p65 (an active form of NF-kB) with the p2x3r gene promoter region and p65 expression were enhanced significantly in diabetes. The inhibition of p65 signaling using the NF-kB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector-p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity.

Wheel defects on trains, such as flat wheels and out-of-roundness, inevitably jeopardize the safety of railway operations. Regular visual inspection and checking by experienced workers are the commonly adopted practice to identify wheel defects. However, the defects may not be spotted in time. Therefore, an automatic, remote-sensing, reliable, and accurate monitoring system for wheel condition is always desirable. The paper describes a real-time system to monitor wheel defects based on fiber Bragg grating sensors. Track strain response upon wheel-rail interaction is measured and processed to generate a condition index which directly reflects the wheel condition. This approach is verified by extensive field test, and the preliminary results show that this electromagneticimmune system provides an effective alternative for wheel defects detection. The system significantly increases the efficiency of maintenance management and reduces the cost for defects detection, and more importantly, avoids derailment timely.

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Introduction Icariin has been shown to improve penile hemodynamics in animal models of erectile dysfunction from cavernous nerve injury and castration. The effects of icariin on penile hemodynamics in diabetic animals remain to be determined. Transforming growth factor β1 (TGFβ1) has been implicated in the pathogenesis of diabetes-related erectile dysfunction. Aim The aim of this study was to investigate the effects of icariin in the penis of streptozotocin (STZ)-induced diabetic rat. Methods Two-month-old Sprague–Dawley male rats received one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16-hour fast. Three days later, the STZ-induced diabetic rats were randomly divided into four groups and were treated with daily gavage feedings of a 50:50 mix of normal saline and dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO at doses of 1, 5, and 10 mg/kg for 3 months. A positive control group underwent IP injection of saline followed by daily gavage of saline/DMSO solution. Treatment was stopped 1 week prior to functional assay and euthanasia. Main Outcome Measure Penile hemodynamics was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was studied using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay (ELISA) to assess the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and TGFβ1/Smad2 signaling pathway. Results Diabetes attenuated ICP response in control animals. Untreated diabetic animals had decreased smooth muscle/collagen ratio and endothelial cell content in the corpora cavernosa; treatment with icariin partially attenuating these effects. Icariin-treated animals also had a significantly greater expression of nicotinamide adenine dinucleotide phosphate-positive nerves and the endothelial cell markers, von Willebrand factor (vWF), and platelet endothelial cell adhesion molecule-1 (PECAM). TGFβ1/Smad2 signaling pathway was down-regulated in the penis from icariin-treated models relative to what was observed in negative control animals. Conclusion Icariin treatment preserved penile hemodynamics, smooth muscle and endothelial integrity, and neuronal nitric oxide synthase expression in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2 signaling pathway might mediate this effect.