Interplay between geometry and flow distribution in an airway tree

Uniform fluid flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. This is found by direct numerical simulation of the Navier-Stokes equations in a 3D tree geometry. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure uniform fluid distribution in a tree. This study suggests that any non-uniformity in the air flow distribution in human lungs should be influenced by the respiratory conditions, rest or hard exercise

Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow

We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow for different flow geometries. When moving between two parallel plates or in a cylindrical microchannel, the swimmer performs either periodic swinging or periodic tumbling motion. Although the trajectories of spherical and elongated swimmers are qualitatively similar, the swinging and tumbling frequency strongly depends on the aspect ratio of the swimmer. In channels with reduced symmetry the swimmers perform quasiperiodic motion which we demonstrate explicitely for swimming in a channel with elliptical cross section

Carbonates from the ancient world's longest aqueduct:A testament of Byzantine water management

The fourth‐ and fifth‐century aqueduct system of Constantinople is, at 426 km, the longest water supply line of the ancient world. Carbonate deposits in the aqueduct system provide an archive of both archaeological developments and palaeo‐environmental conditions during the depositional period. The 246‐km‐long aqueduct line from the fourth century used springs from a small aquifer, whereas a 180‐km‐long fifth‐century extension to the west tapped a larger aquifer. Although historical records testify at least 700 years of aqueduct activity, carbonate deposits in the aqueduct system display less than 27 years of operation. This implies that the entire system must have been cleaned of carbonate, presumably during regular campaigns. A 50‐km‐long double‐aqueduct section in the central part of the system may have been a costly but practical solution to allow repairs and cleaning of the aqueducts of carbonate to ascertain a continuous water supply to the city. The fifth‐century channel was commonly contaminated with clay, caused by the nature of the aqueduct system and possible local damage to the channel. This clay‐rich water could have been one of the reasons for the construction of large reservoirs in Constantinople. imageLeverhulme Trust http://dx.doi.org/10.13039/501100000275Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/50110000165

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively

A re-evaluation of phylogenomic data reveals that current understanding in wheat blast population biology and epidemiology is obfuscated by oversights in population sampling.

Abstract: Wheat blast, caused by the Pyricularia oryzae Triticum lineage (PoT), first emerged in Brazil and quickly spread to neighboring countries. Its recent appearance in Bangladesh and Zambia highlights a need to understand the disease's population biology and epidemiology so as to mitigate pandemic outbreaks. Current knowledge is mostly based on characterizations of Brazilian wheat blast isolates and comparison with isolates from non-wheat, endemic grasses. These foregoing studies concluded that the wheat blast population lacks host specificity and, as a result, undergoes extensive gene flow with populations infecting non-wheat hosts. Additionally, based on genetic similarity between wheat blast and isolates infecting Urochloa species, it was proposed that the disease originally emerged via a host jump from this grass, and that Urochloa likely plays a central role in wheat blast epidemiology, owing to its widespread use as a pasture grass. However, due to inconsistencies with broader phylogenetic studies, we suspected that these seminal studies hadn't actually sampled the populations normally found on endemic grasses and, instead, had repeatedly isolated members of PoT and the related Lolium pathogen lineage (PoL1). Re-analysis of the Brazilian data as part of a comprehensive, global, phylogenomic dataset that included a small number of S. American isolates sampled away from wheat confirmed our suspicion and identified four new P. oryzae lineages on grass hosts. As a result, the conclusions underpinning current understanding in wheat blast's evolution, population biology and epidemiology are unsubstantiated and could be equivocal