922017 research outputs found
Sort by
Understanding the Effects of Zn Injection and OLNC-Treatment on 316 Stainless Steel Oxide under Simulated BWR Conditions
No full textThis study investigates the mechanism of incorporation of metal cations (Zn and Co) into the 316 stainless steel (SS) oxide under hydrogenated water chemistry (HWC) and On-Line NobleChemTM (OLNC). Coupons of 316 SS were exposed to simulated boiling water reactor (BWR) conditions (pure water, H:O molar ratio ~8) at 288 °C and then analysed via surface characterisation techniques. Specifically, coupons were initially exposed under HWC conditions for 500 h, then subjected for 200 h to the OLNCtreatment, and then a final exposure under HWC conditions for 500 h, all with simultaneous monitoring of the electrochemical corrosion potential. These exposures were performed both with and without Zn and or Co injection. It was found that Zn decreased the oxide thickness of the inner oxide layer and decreased the size of the crystallites on the outer layer. Addition of 0.2 ppb of Co in the water chemistry containing 10 ppb Zn did not appear to influence the oxide morphology nor its composition. Hard X-ray XPS analysis showed that Zn did not completely suppress Co incorporation in the outer oxide layer which was still found in concentrations up to 0.6 at. % on the surface of the oxide under Zn addition conditions
Effects of Sensor Design on the Performance of Wearable Sweat Monitors
No full textWearable sweat sensors are rapidly emerging for continuous and noninvasive monitoring of ‘wet’ parameters not included in current commercial wearables. This paper investigates the optimization of screen printed sweat sensors, intended to ultimately be compatible with large scale, roll-to-roll, fabrication. Sweat sensors containing Na+, K+ ion selective electrodes and pH sensing elements were screen printed on polyethylene naphthalate films with different electrode array designs. For sensing Na+ ions, a PEDOT:PSS transducer layer was found to effectively improve the sensor performance, showing an up to 32% sensitivity enhancement of up to 113.3mV/decade. Large working electrode sensing area was found to play an important role in achieving high electrical sensitivity, and the position of the electrodes influenced the individual sensor performance. These findings provide a solid foundation for an optimized development on wearable sweat sensors
Randomized, Phase II Study of Selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer.
No full textIntroductionCisplatin and gemcitabine (CisGem) is standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomized phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem.MethodsPatients with advanced BTC received CisGem; arm A included selumetinib every day, arm B: selumetinib, days 1-5, 8-19 each cycle. Arm C received CisGem alone. Selumetinib was dosed at 75mg BID but amended to 50mg BID due to toxicity. Results51 participants were evaluable for response. No significant difference was seen in mean change in tumor size at 10 weeks between Arm A and C (-7.8% vs -12.8%, p=0.54) or arm B and C (-15% vs -12.8%, p=0.78). There was no difference in median progression-free survival (6.0, 7.0, 6.3 months, p>0.95) or overall survival (11.7, 11.7, 12.8 months, p=0.70) for arms A, B and C, respectively. More participants experienced grade 3-4 toxicities in selumetinib-containing arms. More participants in arm A required chemotherapy dose reductions (p=0.01) with lower chemotherapy dose intensity during the first 10 weeks.ConclusionAdding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC
Endoscopic surveillance alone is feasible and safe in type I gastric neuroendocrine neoplasms less than 10mm in diameter
No full textPurposeType I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs.MethodsRetrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003-2019.ResultsFollowing initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11mm g-NENs.ConclusionsPatients with ≤10mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2-3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma
ADBSat: Verification and validation of a novel panel method for quick aerodynamic analysis of satellites
No full textWe present the validation of ADBSat, a novel implementation of the panel method including a fast pseudo-shading algorithm, that can quickly and accurately determine the forces and torques on satellites in free-molecular flow. Our main method of validation is comparing test cases between ADBSat, the current de facto standard of direct simulation Monte Carlo (DSMC), and published literature. ADBSat exhibits a significantly shorter runtime than DSMC and performs well, except where deep concavities are present in the satellite models. The shading algorithm also experiences problems when a large proportion of the satellite surface area is oriented parallel to the flow, but this can be mitigated by examining the body at small angles to this configuration (± 0.1◦). We recommend that an error interval on ADBSat outputs of up to 3% is adopted. Therefore, ADBSat is a suitable tool for quickly determining the aerodynamic characteristics of a wide range of satellite geometries in different environmental conditions in VLEO. It can also be used in a complementary manner to identify cases that warrant further investigation using other numerical-based methods.<br/
Cluster Model Study into the Catalytic Mechanism of α-Ketoglutarate Biodegradation by the Ethylene-Forming-Enzyme Reveals Structural Differences with Nonheme Iron Hydroxylases
No full textEthylene is an important signaling molecule in plants that triggers the growth of leaves, flowers and fruits. One of the enzymes involved in the biosynthesis of ethylene is the ethylene-forming enzyme (EFE), which is an usual nonheme iron enzyme that biodegrades α-ketoglutarate to three CO2 molecules and ethylene. As the detailed mechanism of EFE and its biosynthesis of ethylene remains controversial and particularly the function of the co-substrate L-arginine, we decided to pursue a density functional theory study on possible pathways of the enzyme leading to its ethylene biosyn-thesis and test many possible pathways and mechanisms. A large active site cluster model of 322 atoms was created that contains all features of the first- and second-coordination sphere of the active site and substrate (α-ketoglutarate) binding pockets. The calculations identify a persuccinate intermediate that triggers a bifurcation pathway in the enzyme and either reacts with a molecule of CO2 to form carbonate or forms a high-valent iron(IV)-oxo species through heterolytic dioxygen bond cleavage. Our studies show that both bifurcation pathways converge to the same intermediate again and can lead to ethylene products, although the two pathways have different kinetics. Interestingly, our studies also show that the iron(IV)-oxo itself can form carbonate and ethylene but through much higher barriers. As a matter of fact, these barriers are higher in energy than typical aliphatic hydroxylation barriers and may not be competitive with arginine hydroxylation. Inclusion of L-arginine co-substrate into the model leads to minor changes in the structure and fold and its charge and dipole moment does not seem to affect the first stage of the catalytic cycle. Moreover, key activation barriers appear little affected by the inclusion of L-arginine into the model. We, therefore, believe that L-arginine’s role is to lock α-ketoglutarate and its products into a tight binding pocket to enable its degradation and to prevent early release of CO2. Our studies show that due to distinct differences in α-ketoglutarate positioning between different arginine activating nonheme iron dioxygenases in the co-substrate binding pocket and its tighter binding in EFE, we predict that the release of CO2 is prevented in the first stage of the oxygen activation mechanism. This enables attack of CO2 on a persuccinate complex to form carbonate products leading to ethylene formation. The work gives suggestions on the engineering of EFE into a hydroxylase or improve the ethylene biosynthesis
Governance choice misfit and firm performance in offshoring innovation: The role of institutional environment
No full textIn this paper, we analyse the effect of institutional factors on the relationship between governance choices and business outcomes when offshoring innovation. Grounded in an institutional theory perspective, we use survey data from the ORN database to estimate regression models and identify governance modes related to specific drivers of offshore innovation. We then analyse the effect on firm performance of choosing a governance mode not in line with the one predicted by the model. We find that choosing a fully owned offshoring operation when theory would predict selecting offshore outsourcing has a negative effect on performance, but not vice versa. We also find that institutional factors of rule of law and IPR protection strength in host countries negatively affect firm performance when offshoring innovation activities
Properties of positive feedback interconnected negative imaginary systems
No full textThis paper addresses the problem of finding a set of ‘if and only if’ criteria for a positive feedback interconnection of two Negative Imaginary (NI) systems to retain the NI property.First, we have derived a state-space characterisation for NI systems that does not impose the minimality restriction. Then, two more essential pre-requisite technical lemmas are provided to prove the main results of this paper, which deal with interconnected system properties. Under some technical assumptions, the paper shows that a positive feedback interconnection of two NI systems with possible pole(s) at s = 0 preserves the NI property.Subsequently, the result is specialised when the NI systems do not have any pole(s) at s = 0 and then to SNI systems. The proposed results have potential applications in decentralised control of large vehicle platoons. Furthermore, the results may be utilised in simplifying complex physical networks and in physical network analysis and synthesis
Mitochondrial antiviral-signalling protein is a client of the BAG6 protein quality control complex
No full textThe heterotrimeric BAG6 complex coordinates the direct handover of newly synthesised tail-anchored (TA) membrane proteins from an SGTA-bound preloading complex to the endoplasmic reticulum (ER) delivery component TRC40. In contrast, defective precursors, including aberrant TA proteins, form a stable complex with this cytosolic protein quality control factor, enabling such clients to be either productively re-routed or selectively degraded. We identify the mitochondrial TA protein MAVS (mitochondrial antiviral-signalling protein) as an endogenous client of both SGTA and the BAG6 complex. Our data suggest that the BAG6 complex binds to a cytosolic pool of MAVS before its misinsertion into the ER membrane, from where it can subsequently be removed via ATP13A1-mediated dislocation. This BAG6- associated fraction of MAVS is dynamic and responds to the activation of an innate immune response, suggesting that BAG6 may modulate the pool of MAVS that is available for coordinating the cellular response to viral infection
Numerical Stability of Algorithms at Extreme Scale and Low Precisions*
No full textThe largest dense linear systems that are being solved today are of order 𝑛 = 107. Single precision arithmetic, which has a unit roundoff 𝑢 ≈ 10-8, is widely used in scientific computing, and half precision arithmetic, with 𝑢 ≈ 10−4, is increasingly being exploited as it becomes more readily available in hardware. Standard rounding error bounds for numerical linear algebra algorithms are proportional to 𝑝(𝑛)𝑢, with 𝑝 growing at least linearly with 𝑛. Therefore we are at the stage where these rounding error bounds are not able to guarantee any accuracy or stability in the computed results for some extreme-scale or low-accuracy computations. We explain how rounding error bounds with much smaller constants can be obtained. Blocked algorithms, which break the data into blocks of size 𝑏, lead to a reduction in the error constants by a factor 𝑏 or more. Two architectural features also reduce the error constants: extended precision registers and fused multiply–add operations, either at the scalar level or in mixed precision block form. We also discuss a new probabilistic approach to rounding error analysis that provides error constants that are the square roots of those of the worst-case bounds. Combining these different considerations provides new understanding of the numerical stability of extreme scale and low precision computations in numerical linear algebra.<br/