Convective Fingering of an Autocatalytic Reaction Front

We report experimental observations of the convection-driven fingering instability of an iodate-arsenous acid chemical reaction front. The front propagated upward in a vertical slab; the thickness of the slab was varied to control the degree of instability. We observed the onset and subsequent nonlinear evolution of the fingers, which were made visible by a {\it p}H indicator. We measured the spacing of the fingers during their initial stages and compared this to the wavelength of the fastest growing linear mode predicted by the stability analysis of Huang {\it et. al.} [{\it Phys. Rev. E}, {\bf 48}, 4378 (1993), and unpublished]. We find agreement with the thickness dependence predicted by the theory.Comment: 11 pages, RevTex with 3 eps figures. To be published in Phys Rev E, [email protected], [email protected], [email protected]

ENDO-Pore:high-throughput linked-end mapping of single DNA cleavage events using nanopore sequencing

Mapping the precise position of DNA cleavage events plays a key role in determining the mechanism and function of endonucleases. ENDO-Pore is a high-throughput nanopore-based method that allows the time resolved mapping single molecule DNA cleavage events in vitro. Following linearisation of a circular DNA substrate by the endonuclease, a resistance cassette is ligated recording the position of the cleavage event. A library of single cleavage events is constructed and subjected to rolling circle amplification to generate concatemers. These are sequenced and used to produce accurate consensus sequences. To identify the cleavage site(s), we developed CSI (Cleavage Site Investigator). CSI recognizes the ends of the cassette ligated into the cleaved substrate and triangulates the position of the dsDNA break. We firstly benchmarked ENDO-Pore using Type II restriction endonucleases. Secondly, we analysed the effect of crRNA length on the cleavage pattern of CRISPR Cas12a. Finally, we mapped the time-resolved DNA cleavage by the Type ISP restriction endonuclease LlaGI that introduces random double-strand breaks into its DNA substrates

Power transformer dissolved gas analysis through Bayesian networks and hypothesis testing

Accurate diagnosis of power transformers is critical for the reliable and cost-effective operation of the power grid. Presently there are a range of methods and analytical models for transformer fault diagnosis based on dissolved gas analysis. However, these methods give conflicting results and they are not able to generate uncertainty information associated with the diagnostics outcome. In this situation it is not always clear which model is the most accurate. This paper presents a novel multiclass probabilistic diagnosis framework for dissolved gas analysis based on Bayesian networks and hypothesis testing. Bayesian network models embed expert knowledge, learn patterns from data and infer the uncertainty associated with the diagnostics outcome, and hypothesis testing aids in the data selection process. The effectiveness of the proposed framework is validated using the IEC TC 10 dataset and is shown to have a maximum diagnosis accuracy of 88.9%

Improving the accuracy of transformer DGA diagnosis in the presence of conflicting evidence

Transformers are critical assets for the reliable and cost-effective operation of the power grid. Transformers may fail if condition monitoring does not identify degraded conditions in time. Dissolved Gas Analysis (DGA) focuses on the examination of the dissolved gasses in the transformer oil and there exist different methods for transformer fault diagnosis based on different analyses of the gassing levels. However, these methods can give conflicting results, and it is not always clear which model is most accurate in a given situation. This paper presents a novel evidence combination framework for DGA based on Bayesian networks. Bayesian network models embed expert knowledge along with learned data patterns and evidence combination which aids in the consistency of analysis. The effectiveness of the proposed framework is validated using the IEC TC 10 dataset with a maximum diagnosis accuracy of 88.3%

Onset of Surface-Tension-Driven Benard Convection

Experiments with shadowgraph visualization reveal a subcritical transition to a hexagonal convection pattern in thin liquid layers that have a free upper surface and are heated from below. The measured critical Marangoni number (84) and observation of hysteresis (3%) agree with theory. In some experiments, imperfect bifurcation is observed and is attributed to deterministic forcing caused in part by the lateral boundaries in the experiment.Comment: 4 pages. The RevTeX file has a macro allowing various styles. The appropriate style is "mypprint" which is the defaul

Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection

Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma

BACKGROUND: Glaucoma is a complex, multifactorial disease characterised by the loss of retinal ganglion cells and their axons leading to a decrease in visual function. The earliest events that damage retinal ganglion cells in glaucoma are currently unknown. Retinal ganglion cell death appears to be compartmentalised, with soma, dendrite and axon changes potentially occurring through different mechanisms. There is mounting evidence from other neurodegenerative diseases suggesting that neuronal dendrites undergo a prolonged period of atrophy, including the pruning of synapses, prior to cell loss. In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases. RESULTS: Using a genetic (DBA/2J mouse) and an inducible (rat microbead) model of glaucoma we first demonstrate that there is loss of retinal ganglion cell synapses and dendrites at time points that precede axon or soma loss. We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. Using a genetic knockout of C1qa (D2.C1qa (-/-) mouse) or pharmacological inhibition of C1 (in the rat bead model) we show that inhibition of C1 is sufficient to preserve dendritic and synaptic architecture. CONCLUSIONS: This study further supports assessing the potential for complement-modulating therapeutics for the prevention of retinal ganglion cell degeneration in glaucoma. Mol Neurodegener 2016 Apr 6; 11(2):2

A novel system for the classification of diseased retinal ganglion cells

Retinal ganglion cell (RGC) dendritic atrophy is an early feature of many forms of retinal degeneration, providing a challenge to RGC classification. The characterization of these changes is complicated by the possibility that selective labeling of any particular class can confound the estimation of dendritic remodeling. To address this issue we have developed a novel, robust, and quantitative RGC classification based on proximal dendritic features which are resistant to early degeneration. RGCs were labeled through the ballistic delivery of DiO and DiI coated tungsten particles to whole retinal explants of 20 adult Brown Norway rats. RGCs were grouped according to the Sun classification system. A comprehensive set of primary and secondary dendrite features were quantified and a new classification model derived using principal component (PCA) and discriminant analyses, to estimate the likelihood that a cell belonged to any given class. One-hundred and thirty one imaged RGCs were analyzed; according to the Sun classification, 24% (n = 31) were RGCA, 29% (n = 38) RGCB, 32% (n = 42) RGCC, and 15% (n = 20) RGCD. PCA gave a 3 component solution, separating RGCs based on descriptors of soma size and primary dendrite thickness, proximal dendritic field size and dendritic tree asymmetry. The new variables correctly classified 73.3% (n = 74) of RGCs from a training sample and 63.3% (n = 19) from a hold out sample indicating an effective model. Soma and proximal dendritic tree morphological features provide a useful surrogate measurement for the classification of RGCs in disease. While a definitive classification is not possible in every case, the technique provides a useful safeguard against sample bias where the normal criteria for cell classification may not be reliable

Live imaging the foreign body response in zebrafish reveals how dampening inflammation reduces fibrosis

Implanting biomaterials in tissues leads to inflammation and a foreign body response (FBR), which can result in rejection. Here, we live image the FBR triggered by surgical suture implantation in a translucent zebrafish model and compare with an acute wound response. We observe inflammation extending from the suture margins, correlating with subsequent avascular and fibrotic encapsulation zones: sutures that induce more inflammation result in increased zones of avascularity and fibrosis. Moreover, we capture macrophages as they fuse to become multinucleate foreign body giant cells (FBGCs) adjacent to the most pro-inflammatory sutures. Genetic and pharmacological dampening of the inflammatory response minimises the FBR (including FBGC generation) and normalises the status of the tissue surrounding these sutures. This model of FBR in adult zebrafish allows us to live image the process and to modulate it in ways that may lead us towards new strategies to ameliorate and circumvent FBR in humans. This article has an associated First Person interview with the first author of the paper