Orthopoxvirus Genome Evolution: The Role of Gene Loss

Poxviruses are highly successful pathogens, known to infect a variety of hosts. The family Poxviridae includes Variola virus, the causative agent of smallpox, which has been eradicated as a public health threat but could potentially reemerge as a bioterrorist threat. The risk scenario includes other animal poxviruses and genetically engineered manipulations of poxviruses. Studies of orthologous gene sets have established the evolutionary relationships of members within the Poxviridae family. It is not clear, however, how variations between family members arose in the past, an important issue in understanding how these viruses may vary and possibly produce future threats. Using a newly developed poxvirus-specific tool, we predicted accurate gene sets for viruses with completely sequenced genomes in the genus Orthopoxvirus. Employing sensitive sequence comparison techniques together with comparison of syntenic gene maps, we established the relationships between all viral gene sets. These techniques allowed us to unambiguously identify the gene loss/gain events that have occurred over the course of orthopoxvirus evolution. It is clear that for all existing Orthopoxvirus species, no individual species has acquired protein-coding genes unique to that species. All existing species contain genes that are all present in members of the species Cowpox virus and that cowpox virus strains contain every gene present in any other orthopoxvirus strain. These results support a theory of reductive evolution in which the reduction in size of the core gene set of a putative ancestral virus played a critical role in speciation and confining any newly emerging virus species to a particular environmental (host or tissue) niche

POEM: Pricing Longer for Edge Computing in the Device Cloud

Multiple access mobile edge computing has been proposed as a promising technology to bring computation services close to end users, by making good use of edge cloud servers. In mobile device clouds (MDC), idle end devices may act as edge servers to offer computation services for busy end devices. Most existing auction based incentive mechanisms in MDC focus on only one round auction without considering the time correlation. Moreover, although existing single round auctions can also be used for multiple times, users should trade with higher bids to get more resources in the cascading rounds of auctions, then their budgets will run out too early to participate in the next auction, leading to auction failures and the whole benefit may suffer. In this paper, we formulate the computation offloading problem as a social welfare optimization problem with given budgets of mobile devices, and consider pricing longer of mobile devices. This problem is a multiple-choice multi-dimensional 0-1 knapsack problem, which is a NP-hard problem. We propose an auction framework named MAFL for long-term benefits that runs a single round resource auction in each round. Extensive simulation results show that the proposed auction mechanism outperforms the single round by about 55.6% on the revenue on average and MAFL outperforms existing double auction by about 68.6% in terms of the revenue.Comment: 8 pages, 1 figure, Accepted by the 18th International Conference on Algorithms and Architectures for Parallel Processing (ICA3PP

Xishuangbanna cucumber landraces and associated traditional knowledge

The Xishuangbanna cucumber variety (XC), Cucumis sativus var. xishuangbannanesis, has been cultivated, managed and used for many generations by ethnic people in Xishuangbanna Prefecture, South Yunnan, China. It has become a significant crop landrace in local communities. An ethnobotanical investigation was conducted in Xishuangbanna in 2017-2018 to collect the agronomic traits of XC and the associated traditional knowledge. The results show that the XC fruit is characterized by its shelf life and delicious flavor. The Dai, Jinuo, Yi, Yao and other ethnic communities were believed to historically possess rich traditional knowledge about XC. Most villagers today, however, did not grow XC and thus their XC genetic resources have been lost together with the traditional knowledge. Only a few households in the remote and high-altitude mountainous villages continue to cultivate very limited amounts of XC for family consumption. The genetic resources of XC and the associated traditional cultures have suffered rapid decline. We suggest that on-farm conservation should be adopted to protect both the genetic resources of XC and the associated traditional knowledge

Multi-Walled Carbon Nanotube-Induced Gene Expression Biomarkers for Medical and Occupational Surveillance

As the demand for multi-walled carbon nanotube (MWCNT) incorporation into industrial and biomedical applications increases, so does the potential for unintentional pulmonary MWCNT exposure, particularly among workers during manufacturing. Pulmonary exposure to MWCNTs raises the potential for development of lung inflammation, fibrosis, and cancer among those exposed; however, there are currently no effective biomarkers for detecting lung fibrosis or predicting the risk of lung cancer resulting from MWCNT exposure. To uncover potential mRNAs and miRNAs that could be used as markers of exposure, this study compared in vivo mRNA and miRNA expression in lung tissue and blood of mice exposed to MWCNTs with in vitro mRNA and miRNA expression from a co-culture model of human lung epithelial and microvascular cells, a system previously shown to have a higher overall genome-scale correlation with mRNA expression in mouse lungs than either cell type grown separately. Concordant mRNAs and miRNAs identified by this study could be used to drive future studies confirming human biomarkers of MWCNT exposure. These potential biomarkers could be used to assess overall worker health and predict the occurrence of MWCNT-induced diseases

Evaluating Soil Resistance Formulations in Thermal‐Based Two‐Source Energy Balance (TSEB) Model: Implications for Heterogeneous Semiarid and Arid Regions

Relatively small fluctuations in the surface energy balance and evapotranspiration in semiarid and arid regions can be indicative of significant changes to ecosystem health. Therefore, it is imperative to have approaches for monitoring surface fluxes in these regions. The remote sensing‐based two‐source energy balance (TSEB) model is a suitable method for flux estimation over sparsely vegetated semiarid and arid landscapes since it explicitly considers surface energy flux contributions from soil and vegetation. However, previous studies indicate that TSEB generally underestimates sensible heat flux (H) and hence overestimates latent heat flux (LE) or evapotranspiration for these regions unless soil resistance coefficients are modified based on additional ground information. In this study, TSEB is applied over semiarid and arid regions on three continents using the original soil resistance formulation with modified coefficients and a recently developed physically based soil resistance formulation. Model sensitivity analysis demonstrates the high sensitivity of TSEB with original soil resistance formulation to soil resistance coefficients, while TSEB with the new soil resistance formulation has relatively low sensitivity to uncertainties in all coefficients. The performance of TSEB using different soil resistance formulations is evaluated by comparing modeled H against eddy covariance measurements in six semiarid and arid study sites and ranking the error statistics. Our results indicate that incorporating the new soil resistance formulation into TSEB would enhance its utility in flux estimation over heterogeneous landscapes by obviating its reliance on semiempirical coefficients and thus provide more robust fluxes over sparsely vegetated regions without model calibration and/or parameter tuning.info:eu-repo/semantics/publishedVersio

Photodynamic Therapy with the Silicon Phthalocyanine Pc 4 Induces Apoptosis in Mycosis Fungoides and Sezary Syndrome

Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4+CD7− malignant T-lymphocytes in the blood relative to CD11b+ monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2

A novel bocavirus in canine liver

Background: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. Findings: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. Conclusions: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal’s complex disease remains to be determined. Keywords: Canine bocavirus 3; Episome; Coinfectio

Real-world utilization patterns and outcomes of colesevelam hcl in the ge electronic medical record

Abstract Background In randomized controlled trials (RCTs), colesevelam HCI, added to other anti-diabetic therapy, reduced hemoglobin A1C by approximately 0.3% to 0.4% over 16- to 26-weeks compared with an increase of approximately 0.1% to 0.2% for placebo, for a placebo-adjusted treatment effect of approximately 0.5%. Evidence on real-world effectiveness is unknown. This retrospective cohort study examined A1C changes following colesevelam HCL initiation in patients with diabetes, regardless of concomitant anti-diabetic medication use. Methods 2000–2011 GE Centricity electronic medical records data were used to identify patients with type 2 diabetes mellitus (T2DM) aged 18 or older initiating colesevelam HCL. The sample was further restricted to uncontrolled patients with database activity ≥ 395 days before and after colesevelam HCL initiation, A1C > 7% during 90 days prior to starting colesevelam HCL, without prior use of bile acid sequestrants, and with at least one A1C result between 42 to 210 days after initiation. Three overlapping time intervals were created for A1C measurement, including 16-weeks, 26-weeks, and 52-weeks following therapy initiation. The last observed A1C lab measurement during each interval was used to define change from baseline. Mean change in A1C was examined using paired t-tests. Sensitivity analyses considered only patients who remained on colesevelam HCL through each respective measurement period, as well as the effect of concomitant diabetes medications. Results Of 1,709,393 patients in the GE database with T2DM, 1,747 met inclusion criteria. The cohort was 58% female, 38% age ≥ 65, and the majority was white. For the 16-week endpoint (N = 1,385), A1C dropped from a mean of 8.22% to 7.75% (mean change −0.47%; P < 0.0001). For the 26- and 52-week endpoints (N = 1,747), A1C dropped from a mean of 8.25% to 7.81% (mean change −0.44%; P < 0.0001) and 8.25% to 7.79% (mean change −0.46%; P < 0.0001), respectively. Sensitivity analyses showed that A1C reductions were of similar direction and magnitude for patients who remained on treatment, and for the subgroups of patients stratified by receipt of concomitant T2DM treatments. Conclusions The 0.44% to 0.47% A1C reduction observed in this study was similar to the reduction observed in RCTs, supporting the real-world effectiveness of colesevelam HCL in reducing A1C

Novel Amdovirus in Gray Foxes

We used viral metagenomics to identify a novel parvovirus in tissues of a gray fox (Urocyon cinereoargenteus). Nearly full genome characterization and phylogenetic analyses showed this parvovirus (provisionally named gray fox amdovirus) to be distantly related to Aleutian mink disease virus, representing the second viral species in the Amdovirus genus

Viral population estimation using pyrosequencing

The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well as for vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used for quantifying this diversity by ultra-deep sequencing of virus samples. We present computational methods for the analysis of such sequence data and apply these techniques to pyrosequencing data obtained from HIV populations within patients harboring drug resistant virus strains. Our main result is the estimation of the population structure of the sample from the pyrosequencing reads. This inference is based on a statistical approach to error correction, followed by a combinatorial algorithm for constructing a minimal set of haplotypes that explain the data. Using this set of explaining haplotypes, we apply a statistical model to infer the frequencies of the haplotypes in the population via an EM algorithm. We demonstrate that pyrosequencing reads allow for effective population reconstruction by extensive simulations and by comparison to 165 sequences obtained directly from clonal sequencing of four independent, diverse HIV populations. Thus, pyrosequencing can be used for cost-effective estimation of the structure of virus populations, promising new insights into viral evolutionary dynamics and disease control strategies.Comment: 23 pages, 13 figure