Large-scale interlaboratory study to develop, analytically validate and apply highly multiplexed, quantitative peptide assays to measure cancer-relevant proteins in plasma

There is an increasing need in biology and clinical medicine to robustly and reliably measure tens-to-hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma, and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and 7 control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to sub-nanogram/mL sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and inter-laboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy isotope labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an inter-laboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality c`ontrol measures, enables sensitive, specific, reproducible and quantitative measurements of proteins and peptides in complex biological matrices such as plasma.

Performance evaluation of non-thermal plasma on particulate matter, ozone and CO2 correlation for diesel exhaust emission reduction

This study is seeking to investigate the effect of non-thermal plasma technology in the abatement of particulate matter (PM) from the actual diesel exhaust. Ozone (O3) strongly promotes PM oxidation, the main product of which is carbon dioxide (CO2). PM oxidation into the less harmful product (CO2) is the main objective whiles the correlation between PM, O3 and CO2 is considered. A dielectric barrier discharge reactor has been designed with pulsed power technology to produce plasma inside the diesel exhaust. To characterise the system under varied conditions, a range of applied voltages from 11 kVPP to 21kVPP at repetition rates of 2.5, 5, 7.5 and 10 kHz, have been experimentally investigated. The results show that by increasing the applied voltage and repetition rate, higher discharge power and CO2 dissociation can be achieved. The PM removal efficiency of more than 50% has been achieved during the experiments and high concentrations of ozone on the order of a few hundreds of ppm have been observed at high discharge powers. Furthermore, O3, CO2 and PM concentrations at different plasma states have been analysed for time dependence. Based on this analysis, an inverse relationship between ozone concentration and PM removal has been found and the role of ozone in PM removal in plasma treatment of diesel exhaust has been highlighted.

Typologies and touchpoints: Designing multi-channel digital strategies

Purpose This study aims to gain a clearer understanding of digital channel design. The emergence of new technologies has revolutionised the way companies interact and engage with customers. The driver for this research was the suggestion that practitioners feel they do not possess the skills to understand and exploit new digital channel opportunities. To gain a clearer understanding of digital channel design, this paper addresses the research question: What digital channels do companies from a wide range of industries and sectors use? Design/methodology/approach A content analysis of 100 international companies was conducted with multiple data sources to form a typology of digital “touchpoints”. The appropriateness of a digital channel typology for this study was for developing rigorous and useful concepts for clarifying and refining the meaning of digital channels. Findings This study identifies what digital channels companies globally currently employ and explores the related needs across industries. A total of 34 digital touchpoints and 4 typologies of digital channels were identified across 16 industries. This research helps to identify the relationship between digital channels and enabling the connections with industry. Research limitations/implications The findings contribute to the growing research area of digital channels. The typology of digital channels is a useful starting point for developing a systematic, theory-based study for enabling the development of broader, comprehensive theories of digital channels. Practical implications Typologies and touchpoints are outlined in relation to industry, company objectives and customer needs to allow businesses to seize opportunities and optimise performance through individual touchpoints. A digital channel model as a key outcome of this research guides practitioners on what touchpoint to implement through an interrelated understanding of industry, company and customer needs. Originality/value This is the first paper to explore a range of industries in relation to their use of digital channels using a unique content analysis. Contributions include clarifying and refining digital channel meaning; identifying and refining the hierarchical relations among digital channels(typologies); and establishing typology and industry relationship model.

Web crippling tests of rivet fastened rectangular hollow flange channel beams under two flange load cases

Recent research on hollow flange beams has led to the development of an innovative rectangular hollow flange channel beam (RHFCB) for use in floor systems. The new RHFCB is a mono-symmetric structural section made by intermittently rivet fastening two torsionally rigid closed rectangular hollow flanges to a web plate element, which allows section optimisation by selecting appropriate combinations of web and flange widths and thicknesses. However, the current design rules for cold-formed steel sections are not directly applicable to rivet fastened RHFCBs. To date, no investigation has been conducted on their web crippling behaviour and strengths. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of rivet fastened RHFCBs under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. It showed that RHFCBs failed by web crippling, flange crushing and their combinations. Comparison of ultimate web crippling capacities with the predictions from the design equations in AS/NZS 4600 and AISI S100 showed that the current design equations are unconservative for rivet fastened RHFCB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of rivet fastened RHFCBs. These equations can also be used to predict the capacities of RHFCBs subject to combined web crippling and flange crushing conservatively. However, new capacity equations were proposed in the case of flange crushing failures that occurred in thinner flanges with smaller bearing lengths. This paper presents the details of this web crippling experimental study of RHFCB sections and the results.

Shear tests of hollow flange channel beams with real support conditions

This paper presents the details of experimental studies on the effect of real support conditions on the shear strength of hollow flange channel beams, known as LiteSteel beams (LSB). The LSB has a unique shape of a channel beam with two rectangular hollow flanges, made using a unique manufacturing process. In many applications in the building industry LSBs are used with only one web side plate (WSP) at their supports. The WSPs are also often not full height plates. Past research studies showed that these real support connections did not provide the required simply supported conditions. Many studies have been carried out to evaluate the behaviour and design of LSBs with simply supported conditions subject to pure bending and predominant shear actions. To date, however, no investigation has been conducted into the effect of real support conditions on the shear strength of LSBs. Hence a detailed experimental study based on 25 shear tests was undertaken to investigate the shear behaviour and strength of LSBs with real support conditions. Simply supported test specimens of LSBs with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. It was found that the effect of using one WSP on the shear behaviour of LSB is significant and there is about 25% shear capacity reduction due to the lateral movement of the bottom flange at the supports. Shear capacity of LSB was also found to decrease when full height WSPs were not used. Suitably improved support connections were developed to improve the shear capacity of LSBs based on test results. Details of the recommended support connections and shear capacity results are given in this paper.

Behaviour and strength of hollow flange channel sections under torsion and bending

Hollow flange channel section is a cold-formed high-strength and thin-walled steel section with a unique shape including two rectangular hollow flanges and a slender web. Due to its mono-symmetric characteristics, it will also be subjected to torsion when subjected to transverse loads in practical applications. Past research on steel beams subject to torsion has concentrated on open sections while very few steel design standards give suitable design rules for torsion design. Since the hollow flange channel section is different from conventional open sections, its torsional behaviour remains unknown to researchers. Therefore the elastic behaviour of hollow flange channel sections subject to uniform and non-uniform torsion, and combined torsion and bending was investigated using the solutions of appropriate differential equilibrium equations. The section torsion shear flow, warping normal stress distribution, and section constants including torsion constant and warping constant were obtained. The results were compared with those from finite element analyses that verified the accuracy of analytical solutions. Parametric studies were undertaken for simply supported beams subject to a uniformly distributed torque and a uniformly distributed transverse load applied away from the shear centre. This paper presents the details of this research into the elastic behaviour and strength of hollow flange channel sections subject to torsion and bending and the results.

Bending and torsion of hollow flange channel beams

The LiteSteel beam (LSB) is a cold-formed high strength steel channel section made of two torsionally rigid closed flanges and a slender web. Due to its mono-symmetric characteristics, its centroid and shear centre do not coincide. The LSBs can be used in floor systems as joists or bearers and in these applications they are often subjected to transverse loads that are applied away from the shear centre. Hence they are often subjected to combined bending and torsion actions. Previous researches on LSBs have concentrated on their bending or shear behaviour and strengths, and only limited research has been undertaken on their combined bending and torsion behaviour. Therefore in this research a series of nine experiments was first conducted on LSBs subject to combined bending and torsion. Three LSB sections were tested to failure under eccentric loading at mid-span, and appropriate results were obtained from seven tests. A special test rig was used to simulate two different eccentricities and to provide accurate simple boundary conditions at the supports. Finite element models of tested LSBs were developed using ANSYS, and the ultimate strengths, failure modes, and load–displacement curves were obtained and compared with corresponding test results. Finite element analyses agreed well with test results and hence the developed models were used in a parametric study to investigate the effects of load locations, eccentricities, and spans on the combined bending and torsion behaviour of LSBs. The interaction between the ultimate bending and torsional moment capacities was studied and a simple design rule was proposed. This paper presents the details of the tests, finite element analyses, and parametric study of LSBs subject to combined bending and torsion, and the results.

Experimental studies of lipped channel beams subject to web crippling under ETF and ITF load cases

Lipped channel beams (LCBs) are commonly used as floor joists and bearers in buildings. However, they are subjected to specific failure modes such as web crippling. Despite considerable web crippling research, recent studies [1-6] have shown that the current web crippling design rules are unable to predict the test capacities under ETF and ITF load cases. In many instances, the predictions by the available design standards such as AISI S100, AS/NZS 4600 and Eurocode 3 Part 1-3 [7-9] are inconsistent. Hence thirty-six tests were conducted to assess the web crippling behaviour and strengths of LCBs under two flange load cases. Experimental web crippling capacities were then compared with the predictions from the current design rules. These comparisons showed that AS/NZS 4600 and AISI S100 design equations are very unconservative for LCB sections under ETF load case and are conservative for ITF load case. Hence improved equations were proposed to determine the web crippling capacities of LCBs. Suitable design rules were also developed using the direct strength method. This paper presents the details of this study and the results including improved design rules.

Building resilient communities: Creating effective multi-channel communication during disaster response and recovery

Our aim is to examine evidence-based strategies to motivate appropriate action and increase informed decision-making during the response and recovery phases of disasters. We combine expertise in communication, consumer psychology and marketing, disaster and emergency management, and law. This poster presents findings from a social media work package, and preliminary findings from the focus group work package on emergency warning message comprehension.

Channel selection in the short-time modulation domain for distant speech recognition

Automatic speech recognition from multiple distant micro- phones poses significant challenges because of noise and reverberations. The quality of speech acquisition may vary between microphones because of movements of speakers and channel distortions. This paper proposes a channel selection approach for selecting reliable channels based on selection criterion operating in the short-term modulation spectrum domain. The proposed approach quantifies the relative strength of speech from each microphone and speech obtained from beamforming modulations. The new technique is compared experimentally in the real reverb conditions in terms of perceptual evaluation of speech quality (PESQ) measures and word error rate (WER). Overall improvement in recognition rate is observed using delay-sum and superdirective beamformers compared to the case when the channel is selected randomly using circular microphone arrays.

Experimental study of cold-formed steel floors made of hollow flange channel section joists under fire conditions

Fire safety plays a vital role in building design because appropriate level of fire safety is important to safeguard lives and property. Cold-formed steel channel sections along with fire-resistive plasterboards are used to construct light-gauge steel frame (LSF) floor systems to provide adequate fire resistance ratings (FRR). It is common practice to use lipped channel sections (LCS) as joists in LSF floor systems, and past research has only considered such systems. This research focuses on adopting improved joist sections such as hollow flange channel (HFC) sections to improve the structural performance and FRR of cold-formed LSF floor systems under standard fire conditions. The structural and thermal performances of LSF floor systems made of a welded HFC, LiteSteel Beams (LSB), with different plasterboard and insulation configurations, were investigated using four full-scale fire tests under standard fires. These fire tests showed that the new LSF floor system with LSB joists improved the FRR in comparison to that of conventional LCS joists. Fire tests have provided valuable structural and thermal performance data of tested floor systems that included time-temperature profiles and failure times, temperatures, and modes. This paper presents the details of the fire tests conducted in this study and their results along with some important findings.

Uniform surface growth of copper oxide nanowires in radiofrequency plasma discharge and limiting factors

The uniform growth of copper oxide nanowires on the top of copper plate has been investigated during the exposure to radiofrequency plasma discharge in respect to plasma properties and its localization. The copper samples of 10 mm radius and 1 mm in thickness were exposed to argon-oxygen plasma created at discharge power of 150 W. After 10 min, almost uniform growth of nanowires was achieved over large surface. There were significant distortions in nanowire length and shape near the edges. Based on the experimental results, we developed a theoretical model, which took into account a balance in heat released at the flow of the current to the nanowire and rejected from the nanowire. This model established a dependence of the maximal length of the nanowire at dependence on the plasma parameters, where the limiting factor for nanowire growth and distortions in distribution are ballistic effects of ions and their local fluxes. In contrast, the plasma heating by potential interactions of species has very little influence on the length and smaller deviations in flux are allowed for uniformity of growth

Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2-ASK1 apoptosis pathways and oxidative stress is mitigated by Srx-Nrf2 anti-oxidant system

Atmospheric pressure gas plasma (AGP) generates reactive oxygen species (ROS) that induce apoptosis in cultured cancer cells. The majority of cancer cells develop a ROS-scavenging anti-oxidant system regulated by Nrf2, which confers resistance to ROS-mediated cancer cell death. Generation of ROS is involved in the AGP-induced cancer cell death of several colorectal cancer cells (Caco2, HCT116 and SW480) by activation of ASK1-mediated apoptosis signaling pathway without affecting control cells (human colonic sub-epithelial myofibroblasts; CO18, human fetal lung fibroblast; MRC5 and fetal human colon; FHC). However, the identity of an oxidase participating in AGP-induced cancer cell death is unknown. Here, we report that AGP up-regulates the expression of Nox2 (NADPH oxidase) to produce ROS. RNA interference designed to target Nox2 effectively inhibits the AGP-induced ROS production and cancer cell death. In some cases both colorectal cancer HT29 and control cells showed resistance to AGP treatment. Compared to AGP-sensitive Caco2 cells, HT29 cells show a higher basal level of the anti-oxidant system transcriptional regulator Nrf2 and its target protein sulfiredoxin (Srx) which are involved in cellular redox homeostasis. Silencing of both Nrf2 and Srx sensitized HT29 cells, leads to ROS overproduction and decreased cell viability. This indicates that in HT29 cells, Nrf2/Srx axis is a protective factor against AGP-induced oxidative stress. The inhibition of Nrf2/Srx signaling should be considered as a central target in drug-resistant colorectal cancer treatments.

Multifunctional three-dimensional T-junction graphene micro-wells: Energy-efficient, plasma-enabled growth and instant water-based transfer for flexible device applications

The “third-generation” 3D graphene structures, T-junction graphene micro-wells (T-GMWs) are produced on cheap polycrystalline Cu foils in a single-step, low-temperature (270 °C), energy-efficient, and environment-friendly dry plasma-enabled process. T-GMWs comprise vertical graphene (VG) petal-like sheets that seemlessly integrate with each other and the underlying horizontal graphene sheets by forming T-junctions. The microwells have the pico-to-femto-liter storage capacity and precipitate compartmentalized PBS crystals. The T-GMW films are transferred from the Cu substrates, without damage to the both, in de-ionized or tap water, at room temperature, and without commonly used sacrificial materials or hazardous chemicals. The Cu substrates are then re-used to produce similar-quality T-GMWs after a simple plasma conditioning. The isolated T-GMW films are transferred to diverse substrates and devices and show remarkable recovery of their electrical, optical, and hazardous NO2 gas sensing properties upon repeated bending (down to 1 mm radius) and release of flexible trasparent display plastic substrates. The plasma-enabled mechanism of T-GMW isolation in water is proposed and supported by the Cu plasma surface modification analysis. Our GMWs are suitable for various optoelectronic, sesning, energy, and biomedical applications while the growth approach is potentially scalable for future pilot-scale industrial production.

UWB channel measurement and data transfer analysis for multiuser Infostation applications

In this paper, the results of the time dispersion parameters obtained from a set of channel measurements conducted in various environments that are typical of multiuser Infostation application scenarios are presented. The measurement procedure takes into account the practical scenarios typical of the positions and movements of the users in the particular Infostation network. To provide one with the knowledge of how much data can be downloaded by users over a given time and mobile speed, data transfer analysis for multiband orthogonal frequency division multiplexing (MB-OFDM) is presented. As expected, the rough estimate of simultaneous data transfer in a multiuser Infostation scenario indicates dependency of the percentage of download on the data size, number and speed of the users, and the elapse time.