Potential role of protease-antiprotease interactions in Perkinsus marinus infection in Crassostrea spp.

Perkinsus marinus causes devastating losses in populations of the eastern oyster (Crassostrea virginica). Our studies have demonstrated that P. marinus secretes extracellular serine proteases which enhance parasite propagation and compromise host defences. Crassostrea virginica. however, possesses several inhibitors of these proteases. The Pacific oyster (C. gigas) is resistant to P. marinus and possesses protease inhibitors with significantly higher specific activities than those in C. virginica. Interestingly, Crassostrea spp. themselves, elaborate metalloprotease activities which can be detected in their plasma, and are increased during P. marinus infections. Together our work suggests that there may be a broad spectrum of humoral host defences that is brought to bear on P. marinus infections by these two Crassostrea species

Multiphase modelling of the effect of fluid shear stress on cell yield and distribution in a hollow fibre membrane bioreactor

We present a simplified two-dimensional model of fluid flow, nutrient transport and cell distribution in a hollow fibre membrane bioreactor, with the aim of exploring how fluid flow can be used to control the distribution and yield of a cell population which is sensitive to both fluid shear stress and nutrient concentration. The cells are seeded in a scaffold in a layer on top of the hollow fibre, only partially occupying the extracapillary space. Above this layer is a region of free-flowing fluid which we refer to as the upper fluid layer. The flow in the lumen and upper fluid layer is described by the Stokes equations, whilst the flow in the porous fibre membrane is assumed to follow Darcy’s law. Porous mixture theory is used to model the dynamics of and interactions between the cells, scaffold and fluid in the cell–scaffold construct. The concentration of a limiting nutrient (e.g. oxygen) is governed by an advection–reaction–diffusion equation in each region. Through exploitation of the small aspect ratio of each region and asymptotic analysis, we derive a coupled system of partial differential equations for the cell volume fraction and nutrient concentration. We use this model to investigate the effect of mechanotransduction on the distribution and yield of the cell population, by considering cases in which cell proliferation is either enhanced or limited by fluid shear stress and by varying experimentally controllable parameters such as flow rate and cell–scaffold construct thickness

Patterns of recruitment and injury in a heterogeneous airway network model

In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air-liquid interfaces, inhibiting gas exchange. This pa- per proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway di- ameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterised by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure (PEEP) reduces the total recruitment time but at the cost of larger stresses exerted on airway walls

Effect of QW growth temperature on the optical properties of blue and green InGaN/GaN QW structures

In this paper we report on the impact that the quantum well growth temperature has on the internal quantum efficiency and carrier recombination dynamics of two sets of InGaN/GaN multiple quantum well samples, designed to emit at 460 and 530 nm, in which the indium content of the quantum wells within each sample set was maintained. Measurements of the internal quantum efficiency of each sample set showed a systematic variation, with quantum wells grown at a higher temperature exhibiting higher internal quantum efficiency and this variation was preserved at all excitation power densities. By investigating the carrier dynamics at both 10 K and 300 K we were able to attribute this change in internal quantum efficiency to a decrease in the non-radiative recombination rate as the QW growth temperature was increased which we attribute to a decrease in incorporation of the point defects.This work was carried out with the financial support of the United Kingdom Engineering and Physical Sciences Research Council under Grant Nos. EP/I012591/1 and EP/H011676/1.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/pssc.20151018

Structure and composition of non-polar (11-20) InGaN nanorings grown by modified droplet epitaxy

Droplets grown by modified droplet epitaxy on non-polar (11-20) surfaces of InGaN epilayers on GaN have been seen to be associated with underlying ring-like structures. This work discusses droplet etching as a possible mechanism for ring formation, and droplet creeping as a possible explanation for the droplets sitting askew of the ring centre. Transmission electron microscopy (TEM) analysis shows the droplets to move along the c-axis, and indicates that they have a very high In content.The authors gratefully acknowledge funding from the Engineering and Physical Sciences Research Council (Grant number EP/M011 682/1).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/pssb.20155263

Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies

Paul Garner and colleagues conducted a systematic review of 80 studies to compare the quality of private versus public ambulatory health care in low- and middle-income countries

An examination of the relationship between hotspots and recombination associated with chromosome 21 nondisjunction

Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A)/Poly(T) fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. These observations led us to ask whether the altered patterns of recombination associated with maternal nondisjunction of chromosome 21 could be explained by differences in the relationship between recombination placement and recombination-related genomic features (i.e., GC content, CpG fraction, Poly(A)/Poly(T) fraction or gene density) on 21q or differential hot-spot usage along the nondisjoined chromosome 21. We found several significant associations between our genomic features of interest and recombination, interestingly, these results were not consistent among recombination types (single and double proximal or distal events). We also found statistically significant relationships between the frequency of hotspots and the distribution of recombination along nondisjoined chromosomes. Collectively, these findings suggest that factors that affect the accessibility of a specific chromosome region to recombination may be altered in at least a proportion of oocytes with MI and MII errors

Carrier localization in the vicinity of dislocations in InGaN

We present a multi-microscopy study of dislocations in InGaN, whereby the same threading dislocation was observed under several microscopes (atomic force microscopy, scanning electron microscopy, cathodoluminescence imaging and spectroscopy, transmission electron microscopy), and its morphological optical and structural properties directly correlated. We achieved this across an ensemble of defects large enough to be statistically significant. Our results provide evidence that carrier localization occurs in the direct vicinity of the dislocation through the enhanced formation of In-N chains and atomic condensates, thus limiting non-radiative recombination of carriers at the dislocation core. We highlight that the localization properties in the vicinity of threading dislocations arise as a consequence of the strain field of the individual dislocation and the additional strain field building between interacting neighboring dislocations. Our study therefore suggests that careful strain and dislocation distribution engineering may further improve the resilience of InGaN-based devices to threading dislocations. Besides providing a new understanding of dislocations in InGaN, this paper presents a proof-of-concept for a methodology which is relevant to many problems in materials science.This project is funded in part by the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 279361 (MACONS). The research leading to these results has received funding from the European Union Seventh Framework Programme under Grant Agreement 312483-ESTEEM2 (Integrated Infrastructure InitiativeI3). F.M. would also like to acknowledge the financial support from EPSRC Doctoral Prize Awards and Cambridge Philosophical Society. M.H. would like to acknowledge support from the Lindemann Fellowship

Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis

Objective: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. Methods: An epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. Results: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10−8 and cg26401028, P = 1.69 × 10−8). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10−7 and P = 1.05 × 10−6, respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). Conclusion: We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low-density lipoprotein receptor–related protein 1. Additional replication experiments in independent sample collections are now needed

Alloy fluctuations at dislocations in III-Nitrides: identification and impact on optical properties

We investigated alloy fluctuations at dislocations in III-Nitride alloys (InGaN and AlGaN). We found that in both alloys, atom segregation (In segregation in InGaN and Ga segregation in AlGaN) occurs in the tensile part of dislocations with an edge component. In InGaN, In atom segregation leads to an enhanced formation of In-N chains and atomic condensates which act as carrier localization centers. This feature results in a bright spot at the position of the dislocation in the CL images, suggesting that non-radiative recombination at dislocations is impaired. On the other hand, Ga atom segregation at dislocations in AlGaN does not seem to noticeably affect the intensity recorded by CL at the dislocation. This study sheds light on why InGaN-based devices are more resilient to dislocations than AlGaN-based devices. An interesting approach to hinder non-radiative recombination at dislocations may therefore be to dope AlGaN with In.ER