Now showing items 41-60 of 630

• #### Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2

A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a–m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a–m in the presence of phosphorus oxychloride. New compounds 4a–m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52–0.88 μM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.
• #### Entropy-driven cell decision-making predicts "fluid-to-solid" transition in multicellular systems

Cellular decision making allows cells to assume functionally different phenotypes in response to microenvironmental cues, with or without genetic change. It is an open question, how individual cell decisions influence the dynamics at the tissue level. Here, we study spatio-temporal pattern formation in a population of cells exhibiting phenotypic plasticity, which is a paradigm of cell decision making. We focus on the migration/resting and the migration/proliferation plasticity which underly the epithelial-mesenchymal transition (EMT) and the go or grow dichotomy. We assume that cells change their phenotype in order to minimize their microenvironmental entropy following the LEUP (Least microEnvironmental Uncertainty Principle) hypothesis. In turn, we study the impact of the LEUP-driven migration/resting and migration/proliferation plasticity on the corresponding multicellular spatiotemporal dynamics with a stochastic cell-based mathematical model for the spatio-temporal dynamics of the cell phenotypes. In the case of the go or rest plasticity, a corresponding mean-field approximation allows to identify a bistable switching mechanism between a diffusive (fluid) and an epithelial (solid) tissue phase which depends on the sensitivity of the phenotypes to the environment. For the go or grow plasticity, we show the possibility of Turing pattern formation for the "solid" tissue phase and its relation with the parameters of the LEUP-driven cell decisions.
• #### Extending an Established Isomorphism between Group Rings and a Subring of the n × n Matrices

In this work, we extend an established isomorphism between group rings and a subring of the n × n matrices. This extension allows us to construct more complex matrices over the ring R. We present many interesting examples of complex matrices constructed directly from our extension. We also show that some of the matrices used in the literature before can be obtained by a direct application of our extended isomorphism.
• #### A promising laser nitriding method for the design of next generation orthopaedic implants: Cytotoxicity and antibacterial performance of titanium nitride (TiN) wear nano-particles, and enhanced wear properties of laser-nitrided Ti6Al4V surfaces

In this study, fibre laser nitriding in open air was applied to the Ti6Al4V alloy in order to improve the wear resistance, thus minimising the generation of wear debris from the surfaces for load-bearing applications. The recent technological advancement to perform the laser nitriding process in open air allows the opportunity to surface-harden any curved and/or specific areas in the hip implants. The laser nitriding process was modulated between the pulsed mode and continuous wave (CW) mode by varying the duty cycle between 60% (pulsed) and 100% (CW). Our experimental investigations were divided into two stages in sequential order: Firstly, to create crack-free, homogenous and golden laser-nitrided surfaces by the proper selection of duty cycle. Secondly, it was to analyse the properties (both physical and chemical) of the wear debris as well as to evaluate their cytotoxicity and antibacterial performance. The laser-nitrided surfaces were characterised and tested using a variety of techniques, incl. optical microscopy, SEM-EDX, XRD, surface roughness and Vickers hardness measurements, as well as tribological tests (i.e. ball-on-disk wear tests and DLS). The wear debris from the laser-nitrided surfaces (collected in the wear tests) were analysed using TEM, XPS and SEM-EDX. Their toxicity was evaluated using in-vitro cell culture with macrophages at two time points (24 h and 48 h). The antibacterial performance was tested in vitro against two of the most commonly implicated pathogens in orthopaedic infection, namely Staphylococcus aureus and Escherichia coli for 24 h. Our findings indicated that the wear resistance of the surfaces after laser nitriding was significantly improved and the amount of wear debris generated was also significantly reduced. The wear particles from the laser-nitrided surfaces were in the nano-sized scale range (0.01 µm to 0.04 µm or 10 nm to 40 nm). They were found to be less toxic towards RAW264.7 macrophages, yet display antimicrobial properties against Staphylococcus aureus, when compared with the larger particles (1.5 µm in size) from the untreated surfaces. It is envisioned that successful fabrication of the non-toxic and highly wear-resistant TiN layer in Ti6Al4V using the open-air laser nitriding technique can enable progress towards the development of metal-on-metal (MoM) hip implants fully made of Ti-based alloys
• #### Two high-order time discretization schemes for subdiffusion problems with nonsmooth data

Two new high-order time discretization schemes for solving subdiffusion problems with nonsmooth data are developed based on the corrections of the existing time discretization schemes in literature. Without the corrections, the schemes have only a first order of accuracy for both smooth and nonsmooth data. After correcting some starting steps and some weights of the schemes, the optimal convergence orders $O(k^{3- \alpha})$ and $O(k^{4- \alpha})$ with $0< \alpha <1$ can be restored for any fixed time $t$ for both smooth and nonsmooth data, respectively. The error estimates for these two new high-order schemes are proved by using Laplace transform method for both homogeneous and inhomogeneous problem. Numerical examples are given to show that the numerical results are consistent with the theoretical results.
• #### The status of hydrogen technologies in the UK: A multi-disciplinary review

Hydrogen has the potential to offer deep decarbonisation across a range of global heavy-emitting sectors. To have an impact on the global energy system, hydrogen technologies must be deployed with greater urgency. This review article facilitates the much needed, multi-disciplinary discussion around hydrogen. In doing so, the paper outlines recent advancements, prevailing challenges and areas of future research concerning hydrogen technologies, policy, regulation and social considerations in a UK setting. Findings suggest that hydrogen will play a significant role in decarbonising several UK sectors whilst simultaneously addressing challenges faced by alternative low-carbon technologies. Optimal production, delivery and storage systems must be developed to accommodate perceived future demand. Whilst this will be largely dictated by scale, efficiency, cost and technological maturity, significant improvements in existing policies and regulation will also be critical. The future role of hydrogen in the UK’s decarbonisation strategy is not clearly defined. In comparison to alternative low- carbon technologies, policy and regulatory support for hydrogen has been minimal. Whilst there is growing evidence concerning the public perception of hydrogen in UK homes, additional research is required given its many potential applications. The findings detailed in this article support the urgency for further multi- disciplinary collaborative research.
• #### Enhanced design of an offgrid PV-battery-methanation hybrid energy system for power/gas supply

Extensive studies have been carried out on various hybrid energy systems (HESs) for providing electricity to off-grid areas. However, a standalone HES that is capable of providing power and gas, has been less studied. In this paper, a standalone Photovoltaic (PV)-battery-methanation HES is proposed to provide adequate, reliable and cost-effective electricity and gas to the local consumers. Identifying a potential solution to maximize the reliability of the system, asked by consumers, and to minimize costs required by the investors is challenging. Bi-level programming is adopted in this study to tackle the pre-mentioned issue. In the outer layer, an optimal design is obtained by means of particle swarm optimization. In the inner layer, an optimal operation strategy is found under the optimal design of the outer layer using sequential quadratic programming. The results indicate that 1) The bi-level programming used in this study can find the optimal solution; 2) The proposed HES is proved to be able to supply power and gas simultaneously. 3) Compared with the right most and leftmost points on Pareto set, the total costs are reduced by 17.77% and 2.16%.
• #### Columnar self-assembly, electrochemical and luminescence properties of basket-shaped liquid crystalline derivatives of Schiff-base-moulded p-tert-butyl-calix[4]arene

A new family of blue-light emitting supramolecular basket-shaped liquid crystalline compounds based on p-tert-butyl-calix[4]arene core to form self-assembly and columnar hexagonal phase.
• #### A Review of Piezoelectric and Magnetostrictive Biosensor Materials for Detection of COVID‐19 and Other Viruses

The spread of the severe acute respiratory syndrome coronavirus has changed the lives of people around the world with a huge impact on economies and societies. The development of wearable sensors that can continuously monitor the environment for viruses may become an important research area. Here, the state of the art of research on biosensor materials for virus detection is reviewed. A general description of the principles for virus detection is included, along with a critique of the experimental work dedicated to various virus sensors, and a summary of their detection limitations. The piezoelectric sensors used for the detection of human papilloma, vaccinia, dengue, Ebola, influenza A, human immunodeficiency, and hepatitis B viruses are examined in the first section; then the second part deals with magnetostrictive sensors for the detection of bacterial spores, proteins, and classical swine fever. In addition, progress related to early detection of COVID‐19 (coronavirus disease 2019) is discussed in the final section, where remaining challenges in the field are also identified. It is believed that this review will guide material researchers in their future work of developing smart biosensors, which can further improve detection sensitivity in monitoring currently known and future virus threats.
• #### Versailles Project on Advanced Materials and Standards interlaboratory study on intensity calibration for x-ray photoelectron spectroscopy instruments using low-density polyethylene

We report the results of a Versailles Project on Advanced Materials and Standards interlaboratory study on the intensity scale calibration of x-ray photoelectron spectrometers using low-density polyethylene (LDPE) as an alternative material to gold, silver, and copper. An improved set of LDPE reference spectra, corrected for different instrument geometries using a quartz-monochromated Al Kα x-ray source, was developed using data provided by participants in this study. Using these new reference spectra, a transmission function was calculated for each dataset that participants provided. When compared to a similar calibration procedure using the NPL reference spectra for gold, the LDPE intensity calibration method achieves an absolute offset of ∼3.0% and a systematic deviation of ±6.5% on average across all participants. For spectra recorded at high pass energies (≥90 eV), values of absolute offset and systematic deviation are ∼5.8% and ±5.7%, respectively, whereas for spectra collected at lower pass energies (<90 eV), values of absolute offset and systematic deviation are ∼4.9% and ±8.8%, respectively; low pass energy spectra perform worse than the global average, in terms of systematic deviations, due to diminished count rates and signal-to-noise ratio. Differences in absolute offset are attributed to the surface roughness of the LDPE induced by sample preparation. We further assess the usability of LDPE as a secondary reference material and comment on its performance in the presence of issues such as variable dark noise, x-ray warm up times, inaccuracy at low count rates, and underlying spectrometer problems. In response to participant feedback and the results of the study, we provide an updated LDPE intensity calibration protocol to address the issues highlighted in the interlaboratory study. We also comment on the lack of implementation of a consistent and traceable intensity calibration method across the community of x-ray photoelectron spectroscopy (XPS) users and, therefore, propose a route to achieving this with the assistance of instrument manufacturers, metrology laboratories, and experts leading to an international standard for XPS intensity scale calibration.
• #### Electrochemically Detecting DNA Methylation in the EN1 gene Promoter: Implications for understanding Ageing and Disease

There is a growing need for biomarkers which predict age-onset pathology. Although this is challenging, the methylome offers significant potential. Cancer is associated with the hypermethylation of many gene promoters, among which are developmental genes. Evolutionary theory suggests developmental genes arbitrate early-late life trade-offs, causing epimutations that increase disease vulnerability. Such genes could predict age related disease. The aim of this work was to optimise an electrochemical procedure for the future investigation of a broad range of ageing related pathologies. An electrochemical approach, which adopted three analytical techniques, was used to investigate DNA methylation in the EN1 gene promoter. Using synthetic single stranded DNA, one technique was able to detect DNA at concentrations as low as 10nM, with methylation status distinguishable at concentrations >25nM. A negative correlation could be observed between % methylation of heterogeneous solution and the key electrochemical parameter, Rct (r = -0.982, p < 0.01). The technique was applied to the breast cancer cell line MCF-7, where a similar correlation was observed (r = -0.965, p < 0.01). These results suggest electrochemistry can effectively measure DNA methylation at low concentrations of DNA. This has implications for the future detection of age-related disease.
• #### Structure and dielectric properties of double A-site doped bismuth sodium titanate relaxor ferroelectrics for high power energy storage applications

The structural and dielectric properties of barium/strontium substituted Bi0.5Na0.5TiO3 were examined in compositions of general formula (Ba0.4Sr0.6TiO3)x(Bi0.5Na0.5TiO3)1-x. An average classic cubic perovskite structure is maintained from x = 0.5 to 1.0. The temperature dependence of dielectric properties of studied compositions shows relaxor-ferroelectric behaviour attributed to the existence of polar nano-regions. Ferroelectric measurements under variable temperature demonstrated two transitions from normal ferroelectric to relaxor-ferroelectric and relaxor-ferroelectric to paraelectric, at the dipole freezing temperature, Tf, and temperature of maximum permittivity, Tm, respectively. The obtained value of Tf coincides with the onset of linear thermal expansion of the cubic unit cell parameter obtained from high resolution powder neutron diffraction data. Careful analysis of the neutron diffraction data revealed no significant change in the average cubic structure from -263 to 150 C. However, changes in the Gaussian variance component of the neutron peak shape, reveal three distinct regions with transitions at about -100 and 100 C corresponding to the beginning and end of the dielectric dispersion seen in the permittivity and loss spectra. This variation in the Gaussian variance parameter is attributed to the activity of the polar nano-regions. The composition (Ba0.4Sr0.6)0.5(Bi0.5Na0.5)0.5TiO3 was found to exhibit the maximum recoverable energy storage density, with a value of 1.618 J cm-3 and 76.9% storage efficiency at a field of 17 kV mm-1.
• #### Multiscale Understanding of Electric Polarization in Poly(vinylidene fluoride)-Based Ferroelectric Polymers

Poly(vinylidene fluoride) (PVDF) and PVDF-based copolymers with trifluoroethylene (PVDF-TrFE) have attracted considerable academic and industrial interest due to their ferroelectric properties, which are only presented in very few polymers. However, the underlying fundamentals of molecular ordering and induced polarizations are complex and not fully understood. Herein, PVDF, PVDF-TrFE and their blends, prepared using melt extrusion and hot pressing, have been selected to obtain controlled case studies with well-defined chain ordering and microstructures. Impedance analysis and terahertz time-domain spectroscopy are exploited to investigate electric polarization in PVDF-based polymers at different length scales. The extruded ferroelectric films show in-plane chain orientation and higher domain wall density compared to hot pressed films with randomly-distributed polymer chains, which favors the polarization at low frequencies (Hz to MHz), as concluded from the higher dielectric constants and more prominent high electric field polarization switching features. However, the domain walls cannot respond at high frequencies, which leads to lower dielectric constants in the extruded films at THz frequencies.
• #### Online conductivity calibration methods for EIT gas/oil in water flow measurement

Electrical Impedance Tomography (EIT) is a fast imaging technique displaying the electrical conductivity contrast of multiphase flow. It is increasingly utilised for industrial process measurement and control. In principle, EIT has to obtain the prior information of homogenous continuous phase in terms of conductivity as a reference benchmark. This reference significantly influences the quality of subsequent multiphase flow measurement. During dynamic industrial process, the conductivity of continuous phase varies due to the effects from the changes of ambient and fluid temperature, ionic concentration, and internal energy conversion in fluid. It is not practical to stop industrial process frequently and measure the conductivity of continuous phase for taking the EIT reference. If without monitoring conductivity of continuous phase, EIT cannot present accurate and useful measurement results. To online calibrate the electrical conductivity of continuous phase and eliminate drift error of EIT measurement, two methods are discussed in this paper. Based on the linear approximation between fluid temperature and conductivity, the first method monitors fluid temperature and indirectly calibrates conductivity. In the second method, a novel conductivity cell is designed. It consists of a gravitational separation chamber with refreshing bypass and grounded shielding plate. The conductivity of continuous phase is directly sensed by the conductivity cell and fed to EIT system for online calibration. Both static and dynamic experiments were conducted to demonstrate the function and accuracy the conductivity cell.
• #### Measurement of vertical oil-in-water two-phase flow using dual-modality ERT–EMF system

Oil-in-water two-phase flows are often encountered in the upstream petroleum industry. The measurement of phase flow rates is of particular importance for managing oil production and water disposal and/or water reinjection. The complexity of oil-in-water flow structures creates a challenge to flow measurement. This paper proposes a new method of two-phase flow metering, which is based on the use of dual-modality system and multidimensional data fusion. The Electrical Resistance Tomography system (ERT) is used in combination with a commercial off-the-shelf Electromagnetic Flow meter (EMF) to measure the volumetric flow rate of each constituent phase. The water flow rate is determined from the EMF with an input of the mean oil-fraction measured by the ERT. The dispersed oil-phase flow rate is determined from the mean oil fraction and the mean oil velocity measured by the ERT cross-correlation velocity profiling. Experiments were carried out on a vertical upward oil-in-water pipe flow, 50 mm inner-diameter test section, at different total liquid flow rates covering the range of 8–16 m3/hr. The oil and water flow rate measurements obtained from the ERT and the EMF are compared to their respective references. The accuracy of these measurements is discussed and the capability of the measurement system is assessed.
• #### A new visualisation and measurement technology for water continuous multiphase flows

This paper reports the performance of a research prototype of a new multiphase flow instrument to noninvasively measure the phase flow rates, with the capability to rapidly image the flow distributions of two- and three-phase (gas and/or oil in water) flows. The research prototype is based on the novel concepts of combining vector Electrical Impedance Tomography (EIT) sensor (for measuring dispersedphase velocity and fraction) with an electromagnetic flow metre (EMF, for measuring continuous-phase velocity with the EIT input) and a gradiomanometer flow-mixture density metre (FDM), in addition to on-line water conductivity, temperature and absolute pressure measurements. EIT–EMF–FDM data fusion embedded in the research prototype, including online calibration/compensation of conductivity change due to the change of fluids' temperature or ionic concentration, enables the determination of mean concentration, mean velocity and hence the mean flow rate of each individual phase based on the measurement of dispersed-phase distributions and velocity profiles. Results from first flow-loop experiments conducted at Schlumberger Gould Research (SGR) will be described. The performance of the research prototype in flow-rate measurements are evaluated by comparison with the flow-loop references. The results indicate that optimum performance of the research prototype for three-phase flows is confined within the measuring envelope 45–100% Water-in-Liquid Ratio (WLR) and 0–45% Gas Volume Fraction (GVF). Within the scope of this joint research project funded by the UK Engineering & Physical Sciences Research Council (EPSRC), only vertical flows with a conductive continuous liquid phase will be addressed.
• #### Imaging of gas–liquid annular flows for underbalanced drilling using electrical resistance tomography

The underbalanced drilling technique, which is also known as managed-pressure drilling, is playing an important role in oil and gas sector, as it reduces common conventional drilling problems such as minimal drilling rates and formation damage, differential sticking and lost circulation. Flow regime monitoring is one of the key topics in annular multiphase flow research, particularly for underbalanced drilling technique. Prediction of the prevailing flow regime in an annulus is of particular importance in the design and installation of underbalanced drilling facilities. Especially, for establishing a suitable pressure drop model based on the characteristics of the active flow regime. The methods of flow regime prediction (or visualisation) in an annulus that are currently in use are very limited, this is evidently due to poor accuracy or they are simply not applicable to underbalanced drilling operation in practice. Therefore, this paper presents a monitoring method, in which Electrical Resistance Tomography (ERT) is used to rapidly image the prevailing flow regime in an annulus with a metallic inner pipe. Experiments were carried out using an air–waterflow loop with a test section 50 mm diameter flow pipe. The two-phase air–waterflow regimes are visualised in the upward vertical annulus with a radius ratio (r/R) 0.4.This paper highlights the visualisation results of only three flow regimes, namely bubble flow, transitional bubble-slug flow and slug flow. The flow regimes are visualised through axial images stacked from50 mm diameter-pixels of 2D tomograms reconstructed with the Conjugate Gradient Method (SCG). Gas volume fraction profiles within the annular flow channel are also illustrated. The profiles are extracted using the Modified Sensitivity coefficient Back-Projection (MSBP) method with a sensitivity matrix generated from a realistic phantom in the finite element method software. The results are compared with visual observations (e.g. photographs) of the active flow regime at the time of ERT measurements.
• #### Evaluation of EIT Systems and Algorithms for Handling Full Void Fraction Range in Two-phase Flow Measurement

In the aqueous-based two-phase flow, if the void fraction of dispersed phase exceeds 0.25, the conventional Electrical Impedance Tomography (EIT) produces a considerable error due to the linear approximation of Sensitivity Back-projection method, which limits the EIT’s wider application in process industry. In this paper, an EIT sensing system which is able to handle full void fraction range in two-phase flow is reported. This EIT system employs a voltage source, conducts true mutual impedance measurement and reconstructs online image with the Modified Sensitivity Back-Projection (MSBP) algorithm. The capability of Maxwell relationship to convey full void fraction is investigated. The limitation of linear sensitivity back-projection method is analysed. The modified sensitivity back-projection algorithm is used to derive relative conductivity change in the evaluation. Series of static and dynamic experiments demonstrate the mean void fraction obtained using this EIT system has a good agreement with reference void fractions over the range from 0 to 1, which would significantly extend the applications of EIT in process measurement.
• #### Measurement of Interphase Forces based on Dual-modality ERT/DP Sensor in Horizontal Two-phase Flow Gas-water

In order to better understand the mechanisms of two-phase flow and the prevailing flow regimes in horizontal pipelines, the evaluation of interphase forces is paramount. This study develops a method to quantitatively estimate the interphase force in two-phase gas-water flow in horizontal pipeline. The electrical resistance tomography technology is used to measure the void fraction, while the differential pressure perpendicular to the horizontal pipe is measured in different flow patterns via a Differential Pressure sensor. The inner pipe diameter is 50 mm, the water flow range from 3.26 m3/h to 7.36 m3/h, the gas flowrate range from 1 to 60 l/min, which covered a range of flow patterns, the absolute pressure range from0.07 MPa to 0.12 MPa. The relationship between the differential pressure drop and interphase force is established, and the effects of these forces on the flow are analyzed. Experimental results indicate that the dual-modality measurement system was successfully provided a quantitative evaluation of inter-phase forces in two-phase horizontal gas-water flow.
• #### Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity

Targeted tissue drug delivery is a challenge in contemporary nanotechnologically driven therapeutic approaches, with the interplay interactions between nanohost and encapsulated drug shaping the ultimate properties of transport, release and efficacy of the drug at its destination. Prompted by the need to pursue the synthesis of such hybrid systems, a family of modified magnetic core-shell mesoporous silica nano-formulations was synthesized with encapsulated quercetin, a natural flavonoid with proven bioactivity. The new nanocarriers were produced via the sol-gel process, using tetraethoxysilane as a precursor and bearing a magnetic core of surface-modified monodispersed magnetite colloidal superparamagnetic nanoparticles, subsequently surface-modified with polyethylene glycol 3000 (PEG3k). The arising nano-formulations were evaluated for their textural and structural properties, exhibiting enhanced solubility and stability in physiological media, as evidenced by the loading capacity, entrapment efficiency results and in vitro release studies of their load. Guided by the increased bioavailability of quercetin in its encapsulated form, further evaluation of the biological activity of the magnetic as well as non-magnetic core-shell nanoparticles, pertaining to their anti-amyloid and antioxidant potential, revealed interference with the aggregation of β-amyloid peptide (Aβ) in Alzheimer’s disease, reduction of Aβ cellular toxicity and minimization of Aβ-induced Reactive Oxygen Species (ROS) generation. The data indicate that the biological properties of released quercetin are maintained in the presence of the host nanocarriers. Collectively, the findings suggest that the emerging hybrid nano-formulations can function as efficient nanocarriers of hydrophobic natural flavonoids in the development of multifunctional nanomaterials toward therapeutic applications.