Human Neutrophil Elastase Degrades SPLUNC1 and Impairs Airway Epithelial Defense against Bacteria

Background:Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare. One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection. However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood. As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).Methodology/Main Results:Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE. To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells. The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi. We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.Conclusions:Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. © 2013 Jiang et al

IFN-gamma is associated with risk of Schistosoma japonicum infection in China.

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection

Performance modelling and analysis of software defined networking

Software Defined Networking (SDN) is an emerging architecture for the next-generation Internet, providing unprecedented network programmability to handle the explosive growth of Big Data driven by the popularisation of smart mobile devices and the pervasiveness of content-rich multimedia applications. In order to quantitatively investigate the performance characteristics of SDN networks, several research efforts from both simulation experiments and analytical modelling have been reported in the current literature. Among those studies, analytical modelling has demonstrated its superiority in terms of cost-effectiveness in the evaluation of large-scale networks. However, for analytical tractability and simplification, existing analytical models are derived based on the unrealistic assumptions that the network traffic follows the Poisson process which is suitable to model non-bursty text data and the data plane of SDN is modelled by one simplified Single Server Single Queue (SSSQ) system. Recent measurement studies have shown that, due to the features of heavy volume and high velocity, the multimedia big data generated by real-world multimedia applications reveals the bursty and correlated nature in the network transmission. With the aim of the capturing such features of realistic traffic patterns and obtaining a comprehensive and deeper understanding of the performance behaviour of SDN networks, this paper presents a new analytical model to investigate the performance of SDN in the presence of the bursty and correlated arrivals modelled by Markov Modulated Poisson Process (MMPP). The Quality-of-Service performance metrics in terms of the average latency and average network throughput of the SDN networks are derived based on the developed analytical model. To consider realistic multi-queue system of forwarding elements, a Priority-Queue (PQ) system is adopted to model SDN data plane. To address the challenging problem of obtaining the key performance metrics, e.g., queue length distribution of PQ system with a given service capacity, a versatile methodology extending the Empty Buffer Approximation (EBA) method is proposed to facilitate the decomposition of such a PQ system to two SSSQ systems. The validity of the proposed model is demonstrated through extensive simulation experiments. To illustrate its application, the developed model is then utilised to study the strategy of the network configuration and resource allocation in SDN networksThis work is supported by the EU FP7 “QUICK” Project (Grant NO. PIRSES-GA-2013-612652) and the National Natural Science Foundation of China (Grant NO. 61303241)

A pancake-shaped nano-aggregate for focusing surface plasmons

We proposed a pancake-shaped nano-aggregate that highly focuses surface plasmons. The structure is a superposition of bowtie-shaped dimers, where surface plasmons are excited, resonated with the structure, and coupled. Surface integral equation method (Poggio-Miller-Chang-Harrington-Wu-Tsai method) is used to predict the performance of the proposed structure. It is a method which can accurately calculate the near-fields of nanoparticles. Based on the numerical prediction, the proposed structure shows an electric field (E-field) enhancement of more than 400 times, which is equivalent to a Raman enhancement factor of more than 2.5 e 10 times. It is promising for single molecule detections using surface-enhanced Raman scattering. The physics of the proposed structure are revealed. It is useful to design nanostructures for high E-field enhancement. © 2012 American Institute of Physics.published_or_final_versio

Measurement of the velocities in the transient acceleration process using all-fiber photonic Doppler velocimetry

Based on analysis of basic photonic Doppler velocimetry (PDV), a formula to measure velocity variation in a single cycle is put forward. PDV has been improved in three aspects, namely, the laser, the detector and the data processing. A measurement system for velocity of the initial stage of a shock motion has been demonstrated. Instantaneous velocity measurements have been performed. The experimental results have a good agreement with the values obtained from the accelerometer. Compared with the traditional fringe method, the proposed method in this paper can identify instantaneous velocity variation. So it is particularly suitable for measuring the velocity in the transient acceleration process of shock waves and detonation waves

Automated adaptive analysis of tagged magnetic resonance images of the mouse heart

The full potential of tagged MRI of the mouse heart for non-invasive evaluation of cardiac mechanics in transgenic animals has not been realized due to excessive user involvement with available image processing algorithms. Therefore, we developed an automated, rapid, high-resolution analysis technique, called High Density Mapping (HDM), that uses spectral correlation to efficiently quantify regional wall deformation, does not entail tracking of individual tags, and involves minimal user interaction. HDM analysis distinguishes regional mechanics in healthy and infarcted mice within 2 minutes. This new method may help promote the practical use of tagged MRI in mice and other species.published_or_final_versio

Investigating the New Zealand Off-Site Manufacturing Industry’s Readiness for Automated Compliance Checking

Numerous automated compliance checking (ACC) approaches have been developed over the last half of the twentieth century. However, little is known as to how well the ACC technology has served the off-site manufacturing (OSM) industry from the end users’ perspective. This paper aims to measure the New Zealand (NZ) OSM industry’s awareness and readiness for ACC and explore a pathway toward wider ACC adoption. It first reports on a survey study in NZ with 44 valid survey responses. It then proposes a high-level roadmap with key actions that can facilitate wider ACC adoption through 16 interviews with international ACC experts and a focus group with nine local OSM stakeholders. The results show that although there is a high demand for automating compliance processes, the OSM industry, especially small and medium enterprises, are not ready to adopt the ACC technology. Suggestions to address this include (1) establish the foundation for broad ACC adoption; (2) boost the development of the ACC technology to expedite its maturity, (3) test the ACC technology under different scenarios and customize it for the NZ context; (4) encourage the government to provide funding and policy support; and (5) promote education and training of both building information modeling (BIM) and ACC to OSM stakeholders. The results can provide software vendors with valuable information about user expectations and requirements to develop ACC products that can better serve NZ OSM projects, and help OSM stakeholders in NZ and countries with similar economic and regulatory structures to understand the technological and nontechnological gaps to better prepare for the ACC technology adoption

Cloning and expression analysis of two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus

BACKGROUND: Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs. RESULTS: We have cloned and characterized two distinct HIF-alpha cDNAs – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp. The deduced gcHIF-1alpha protein is highly similar to the HIF-1alphas (57–68%) from various vertebrate species, while gcHIF-4alpha is a novel isoform, and shows an equivalent degree of amino acid identity (41–47%) to the HIF-1alpha, HIF-2alpha and HIF-3alpha proteins so far described. Parsimony analysis indicated that gcHIF-4alpha is most closely related to the HIF-3alpha proteins. Northern blot analysis showed that mRNA levels of gcHIF-1alpha and gcHIF-4alpha differ substantially under normoxic and hypoxic conditions, while Western blot studies demonstrated that the endogenous protein levels for both gcHIF-1alpha and gcHIF-4alpha are similarly responsive to hypoxia. Our findings suggest that both gcHIF-1alpha and gcHIF-4alpha are differentially regulated at the transcriptional and translational levels. HRE-luciferase reporter assays show that both proteins function as transcription activators and play distinct roles in modulating the hypoxic response in grass carp. CONCLUSION: There are at least two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – in the hypoxia-tolerant grass carp, which are differentially expressed and regulated in different fish organs in response to hypoxic stress. Overall, the results suggest that unique molecular mechanisms operate through these two HIF-alpha isoforms, which underpin the hypoxic response in the hypoxia-tolerant grass carp

Superconducting ECR ion source: From 24-28 GHz SECRAL to 45 GHz fourth generation ECR.

The development of superconducting ECR source with higher magnetic fields and higher microwave frequency is the most straight forward path to achieve higher beam intensity and higher charge state performance. SECRAL, a superconducting third generation ECR ion source, is designed for 24-28 GHz microwave frequency operation with an innovative magnet configuration of sextupole coils located outside the three solenoids. SECRAL at 24 GHz has already produced a number of record beam intensities, such as 40Ar12+ 1.4 emA, 129Xe26+ 1.1 emA, 129Xe30+ 0.36 emA, and 209Bi31+ 0.68 emA. SECRAL-II, an upgraded version of SECRAL, was built successfully in less than 3 years and has recently been commissioned at full power of a 28 GHz gyrotron and three-frequency heating (28 + 45 + 18 GHz). New record beam intensities for highly charged ion production have been achieved, such as 620 eμA 40Ar16+, 15 eμA 40Ar18+, 146 eμA 86Kr28+, 0.5 eμA 86Kr33+, 53 eμA 129Xe38+, and 17 eμA 129Xe42+. Recent beam test results at SECRAL and SECRAL II have demonstrated that the production of more intense highly charged heavy ion beams needs higher microwave power and higher frequency, as the scaling law predicted. A 45 GHz superconducting ECR ion source FECR (a first fourth generation ECR ion source) is being built at IMP. FECR will be the world's first Nb3Sn superconducting-magnet-based ECR ion source with 6.5 T axial mirror field, 3.5 T sextupole field on the plasma chamber inner wall, and 20 kW at a 45 GHz microwave coupling system. This paper will focus on SECRAL performance studies at 24-28 GHz and technical design of 45 GHz FECR, which demonstrates a technical path for highly charged ion beam production from 24 to 28 GHz SECRAL to 45 GHz FECR