101 research outputs found

    Measured impact of crooked traceroute

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    Data collected using traceroute-based algorithms underpins research into the Internetā€™s router-level topology, though it is possible to infer false links from this data. One source of false inference is the combination of per-flow load-balancing, in which more than one path is active from a given source to destination, and classic traceroute, which varies the UDP destination port number or ICMP checksum of successive probe packets, which can cause per-flow load-balancers to treat successive packets as distinct flows and forward them along different paths. Consequently, successive probe packets can solicit responses from unconnected routers, leading to the inference of false links. This paper examines the inaccuracies induced from such false inferences, both on macroscopic and ISP topology mapping. We collected macroscopic topology data to 365k destinations, with techniques that both do and do not try to capture load balancing phenomena.We then use alias resolution techniques to infer if a measurement artifact of classic traceroute induces a false router-level link. This technique detected that 2.71% and 0.76% of the links in our UDP and ICMP graphs were falsely inferred due to the presence of load-balancing. We conclude that most per-flow load-balancing does not induce false links when macroscopic topology is inferred using classic traceroute. The effect of false links on ISP topology mapping is possibly much worse, because the degrees of a tier-1 ISPā€™s routers derived from classic traceroute were inflated by a median factor of 2.9 as compared to those inferred with Paris traceroute

    Civil War Almanac: The Best Civil War Books of All Time

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    For our latest newsstand-only special issue, The Civil War Almanac, we asked a panel of Civil War historiansā€”J. Matthew Gallman, Matthew C. Hulbert, James Marten, and Amy Murrell Taylorā€”for their opinions on a variety of popular topics, including the war\u27s most overrated and underratred commanders, top turning points, most influential women, and best depictions on film. Space constraints prevented us from including their answers to one of the questions we posed: What are the 10 best Civil War books ever published (nonfiction or fiction)? Below are their responses

    Efficacy and Safety of Ciprofloxacin for Prophylaxis of Polyomavirus BK Virusā€“Associated Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

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    Polyoma virus BKā€“induced hemorrhagic cystitis is an important cause of morbidity after hematopoietic stem cell transplantation (HSCT). Fluoroquinolones have been shown in vitro to inhibit BK viral replication by direct inhibition of the BK-encoded DNA gyrase. We hypothesized that extended prophylaxis with ciprofloxacin may decrease the incidence of severe (grades 3 and 4) BK virusā€“associated hemorrhagic cystitis (sBKHC) after HSCT. We retrospectively collected patient and transplant data, as well as incidence of sBKHC, for all consecutive patients undergoing allogeneic HSCT between June 2006 and August 2010 at our institution. Prophylaxis for sBKHC with ciprofloxacin 500 mg orally twice daily from day 0 until day 60 had been instituted in March 2009, delimiting a group receiving ciprofloxacin prophylaxis (CP) or no prophylaxis (NP). We compared the cumulative incidence of sBKHC in CP and NP, including death in absence of sBKHC as a competing risk. Ninety-two consecutive patients were included in the analysis, 44 in CP and 48 in NP. Median age of patients was 50 years (range: 19-70), and 47% received a myeloablative conditioning regimen. The cumulative incidence of sBKHC was significantly reduced in CP (2.6% versus 20.9%, PĀ =Ā .01). Multivariate Cox regression analysis revealed that assignment to CP and concomitant acute graft-versus-host disease (GVHD) were the only factors independently associated with the occurrence of sBKHC. Patients in CP did not experience a higher risk of Clostridium difficile diarrhea and were less likely to develop episodes of bacteremia. Ciprofloxacin prophylaxis appears safe and effective in reducing the incidence of severe BKHC after allogeneic HSCT

    Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings

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    Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1279-x) contains supplementary material, which is available to authorized users

    Investigating the Role of Root Exudates in Recruiting Streptomyces Bacteria to the Arabidopsis thaliana Microbiome

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    Streptomyces species are saprophytic soil bacteria that produce a diverse array of specialized metabolites, including half of all known antibiotics. They are also rhizobacteria and plant endophytes that can promote plant growth and protect against disease. Several studies have shown that streptomycetes are enriched in the rhizosphere and endosphere of the model plant Arabidopsis thaliana. Here, we set out to test the hypothesis that they are attracted to plant roots by root exudates, and specifically by the plant phytohormone salicylate, which they might use as a nutrient source. We confirmed a previously published report that salicylate over-producing cpr5 plants are colonized more readily by streptomycetes but found that salicylate-deficient sid2-2 and pad4 plants had the same levels of root colonization by Streptomyces bacteria as the wild-type plants. We then tested eight genome sequenced Streptomyces endophyte strains in vitro and found that none were attracted to or could grow on salicylate as a sole carbon source. We next used 13CO2 DNA stable isotope probing to test whether Streptomyces species can feed off a wider range of plant metabolites but found that Streptomyces bacteria were outcompeted by faster growing proteobacteria and did not incorporate photosynthetically fixed carbon into their DNA. We conclude that, given their saprotrophic nature and under conditions of high competition, streptomycetes most likely feed on more complex organic material shed by growing plant roots. Understanding the factors that impact the competitiveness of strains in the plant root microbiome could have consequences for the effective application of biocontrol strains

    Insights into toxic prymnesium parvum blooms:The role of sugars and algal viruses

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    Prymnesium parvum is a toxin-producing microalga that causes harmful algal blooms globally, which often result in large-scale fish kills that have severe ecological and economic implications. Although many toxins have previously been isolated from P. parvum, ambiguity still surrounds the responsible ichthyotoxins in P. parvum blooms and the biotic and abiotic factors that promote bloom toxicity. A major fish kill attributed to P. parvum occurred in Spring 2015 on the Norfolk Broads, a low-lying set of channels and lakes (Broads) found on the East of England. Here, we discuss how water samples taken during this bloom have led to diverse scientific advances ranging from toxin analysis to discovery of a new lytic virus of P. parvum, P. parvum DNA virus (PpDNAV-BW1). Taking recent literature into account, we propose key roles for sialic acids in this type of viral infection. Finally, we discuss recent practical detection and management strategies for controlling these devastating blooms

    Soil, senescence and exudate utilisation: characterisation of the Paragon var. spring bread wheat root microbiome

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    Background: Conventional methods of agricultural pest control and crop fertilisation are unsustainable. To meet growing demand, we must find ecologically responsible means to control disease and promote crop yields. The root-associated microbiome can aid plants with disease suppression, abiotic stress relief, and nutrient bioavailability. The aim of the present work was to profile the community of bacteria, fungi, and archaea associated with the wheat rhizosphere and root endosphere in different conditions. We also aimed to use 13CO2 stable isotope probing (SIP) to identify microbes within the root compartments that were capable of utilising host-derived carbon. Results: Metabarcoding revealed that community composition shifted significantly for bacteria, fungi, and archaea across compartments. This shift was most pronounced for bacteria and fungi, while we observed weaker selection on the ammonia oxidising archaea-dominated archaeal community. Across multiple soil types we found that soil inoculum was a significant driver of endosphere community composition, however, several bacterial families were identified as core enriched taxa in all soil conditions. The most abundant of these were Streptomycetaceae and Burkholderiaceae. Moreover, as the plants senesce, both families were reduced in abundance, indicating that input from the living plant was required to maintain their abundance in the endosphere. Stable isotope probing showed that bacterial taxa within the Burkholderiaceae family, among other core enriched taxa such as Pseudomonadaceae, were able to use root exudates, but Streptomycetaceae were not. Conclusions: The consistent enrichment of Streptomycetaceae and Burkholderiaceae within the endosphere, and their reduced abundance after developmental senescence, indicated a significant role for these families within the wheat root microbiome. While Streptomycetaceae did not utilise root exudates in the rhizosphere, we provide evidence that Pseudomonadaceae and Burkholderiaceae family taxa are recruited to the wheat root community via root exudates. This deeper understanding crop microbiome formation will enable researchers to characterise these interactions further, and possibly contribute to ecologically responsible methods for yield improvement and biocontrol in the future
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