Effects of stitching on delamination of satin weave carbon-epoxy laminates under mode I, mode II and mixed-mode I/II loadings

The objective of the present study is to characterize the effect of modified chain stitching on the delamination growth under mixed-mode I/II loading conditions. Delamination toughness under mode I is experimentally determined, for unstitched and stitched laminates, by using untabbed and tabbed double cantilever beam (TDCB) tests. The effect of the reinforcing tabs on mode I toughness is investigated. Stitching improves the energy release rate (ERR) up to 4 times in mode I. Mode II delamination toughness is evaluated in end-notched flexure (ENF) tests. Different geometries of stitched specimens are tested. Crack propagation occurs without any failure of stitching yarns. The final crack length attains the mid-span or it stops before and the specimen breaks in bending. The ERR is initially low and gradually increases with crack length to very high values. The mixedmode delamination behaviour is investigated using a mixed-mode bending (MMB) test. For unstitched specimens, a simple mixed-mode criterion is identified. For stitched specimens, stitching yarns do not break during 25% of mode I ratio tests and the ERR increase is relatively small compared to unstitched values. For 70% and 50% of mode I ratios, failures of yarns are observed during crack propagation and tests are able to capture correctly the effect of the stitching: it clearly improves the ERR for these two mixed modes, as much as threefold

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.

A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii

Peer reviewedPublisher PD

Dynamic design: manipulation of millisecond timescale motions on the energy landscape of cyclophilin A

Proteins need to interconvert between many conformations in order to function, many of which are formed transiently, and sparsely populated. Particularly when the lifetimes of these states approach the millisecond timescale, identifying the relevant structures and the mechanism by which they interconvert remains a tremendous challenge. Here we introduce a novel combination of accelerated MD (aMD) simulations and Markov state modelling (MSM) to explore these ‘excited’ conformational states. Applying this to the highly dynamic protein CypA, a protein involved in immune response and associated with HIV infection, we identify five principally populated conformational states and the atomistic mechanism by which they interconvert. A rational design strategy predicted that the mutant D66A should stabilise the minor conformations and substantially alter the dynamics, whereas the similar mutant H70A should leave the landscape broadly unchanged. These predictions are confirmed using CPMG and R1ρ solution state NMR measurements. By efficiently exploring functionally relevant, but sparsely populated conformations with millisecond lifetimes in silico, our aMD/MSM method has tremendous promise for the design of dynamic protein free energy landscapes for both protein engineering and drug discovery

The WACMOS-ET project, part 2 : evaluation of global terrestrial evaporation data sets

The WAter Cycle Multi-mission Observation Strategy - EvapoTranspiration (WACMOS-ET) project aims to advance the development of land evaporation estimates on global and regional scales. Its main objective is the derivation, validation, and intercomparison of a group of existing evaporation retrieval algorithms driven by a common forcing data set. Three commonly used process-based evaporation methodologies are evaluated: the Penman-Monteith algorithm behind the official Moderate Resolution Imaging Spectroradiometer (MODIS) evaporation product (PM-MOD), the Global Land Evaporation Amsterdam Model (GLEAM), and the Priestley-Taylor Jet Propulsion Laboratory model (PT-JPL). The resulting global spatiotemporal variability of evaporation, the closure of regional water budgets, and the discrete estimation of land evaporation components or sources (i.e. transpiration, interception loss, and direct soil evaporation) are investigated using river discharge data, independent global evaporation data sets and results from previous studies. In a companion article (Part 1), Michel et al. (2016) inspect the performance of these three models at local scales using measurements from eddy-covariance towers and include in the assessment the Surface Energy Balance System (SEBS) model. In agreement with Part 1, our results indicate that the Priestley and Taylor products (PT-JPL and GLEAM) perform best overall for most ecosystems and climate regimes. While all three evaporation products adequately represent the expected average geographical patterns and seasonality, there is a tendency in PM-MOD to underestimate the flux in the tropics and subtropics. Overall, results from GLEAM and PT-JPL appear more realistic when compared to surface water balances from 837 globally distributed catchments and to separate evaporation estimates from ERA-Interim and the model tree ensemble (MTE). Nonetheless, all products show large dissimilarities during conditions of water stress and drought and deficiencies in the way evaporation is partitioned into its different components. This observed inter-product variability, even when common forcing is used, suggests that caution is necessary in applying a single data set for large-scale studies in isolation. A general finding that different models perform better under different conditions highlights the potential for considering biome- or climate-specific composites of models. Nevertheless, the generation of a multi-product ensemble, with weighting based on validation analyses and uncertainty assessments, is proposed as the best way forward in our long-term goal to develop a robust observational benchmark data set of continental evaporation

Switching of magnetic domains reveals evidence for spatially inhomogeneous superconductivity

The interplay of magnetic and charge fluctuations can lead to quantum phases with exceptional electronic properties. A case in point is magnetically-driven superconductivity, where magnetic correlations fundamentally affect the underlying symmetry and generate new physical properties. The superconducting wave-function in most known magnetic superconductors does not break translational symmetry. However, it has been predicted that modulated triplet p-wave superconductivity occurs in singlet d-wave superconductors with spin-density wave (SDW) order. Here we report evidence for the presence of a spatially inhomogeneous p-wave Cooper pair-density wave (PDW) in CeCoIn5. We show that the SDW domains can be switched completely by a tiny change of the magnetic field direction, which is naturally explained by the presence of triplet superconductivity. Further, the Q-phase emerges in a common magneto-superconducting quantum critical point. The Q-phase of CeCoIn5 thus represents an example where spatially modulated superconductivity is associated with SDW order

Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis

Neurodegeneration mediates neurological disability in inflammatory demyelinating diseases of the CNS. The role of innate immune cells in mediating this damage has remained controversial with evidence for destructive and protective effects. This has complicated efforts to develop treatment. The time sequence and dynamic evolution of the opposing functions are especially unclear. Given limits of in vivo monitoring in human diseases such as multiple sclerosis (MS), animal models are warranted to investigate the association and timing of innate immune activation with neurodegeneration. Using noninvasive in vivo retinal imaging of experimental autoimmune encephalitis (EAE) in CX3CR1GFP/+–knock-in mice followed by transcriptional profiling, we are able to show 2 distinct waves separated by a marked reduction in the number of innate immune cells and change in cell morphology. The first wave is characterized by an inflammatory phagocytic phenotype preceding the onset of EAE, whereas the second wave is characterized by a regulatory, antiinflammatory phenotype during the chronic stage. Additionally, the magnitude of the first wave is associated with neuronal loss. Two transcripts identified — growth arrest–specific protein 6 (GAS6) and suppressor of cytokine signaling 3 (SOCS3) — might be promising targets for enhancing protective effects of microglia in the chronic phase after initial injury

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Structural insights into Clostridium perfringens delta toxin pore formation

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins