Developing system models to help Great Britain's railways embrace innovative technologies with confidence

Railways are under pressure to become more efficient and cut their costs; innovation has a part to play in achieving these goals. The railway is, however, a complex and closely coupled system, making it difficult in the early stages of development, to be clear what the system-wide impact of innovation will be. The research covered in this paper stems from the idea that computer-based models of existing systems can help overcome this problem, by providing a baseline framework against which the impact of innovation can be identified. The paper describes development of a repeatable modelling methodology, which elicits\ud objective system data from Railway Group Standards and integrates it using CORE®, a powerful system modelling tool, to create system models. The ability of such models to help identify impacts is verified, using as an example the introduction of RailBAM (a new technology that acoustically monitors the health of rolling stock axle bearings) into the existing hot axle bearing detection system

An augmented delivery of the anticancer agent, curcumin, to the colon

This work describes the formulation aspects of an orally viable curcumin-containing mucoadhesive nanoparticulate system for management of colon cancer. Curcumin is documented to possess anticancer properties whilst modified citrus pectin yields a galactose functionality capable of inhibiting the growth and proliferation of colon cancer cells due to antagonism to galectin-3 (Gal-3). A successfully formulated curcumin containing chitosan-modified citrus pectinate nanoparticles (MCPCNPs) registered a z-average of 178 nm (± 0.896) and a positive surface charge of + 35.7 mV (± 1.41). The MCPCNPs presented high mucoadhesion propensity in the colonic region/ media and minimal at pH 1.2 (stomach). There was approximately 18 % curcumin release at pH 1.2 over 2 h and up to 68% release in the 33% (w/v) caecal medium over 24 h. The data obtained strongly suggests that the formulated MCPCNPs have the potential to be applied as an orally deliverable colon cancer formulation alternative in the treatment of colon cancer

Development of an in vitro system to study the interactions of aerosolized drugs with pulmonary mucus

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium ≈ glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus

Analysis of leaf surfaces using scanning ion conductance microscopy

Leaf surfaces are highly complex functional systems with well defined chemistry and structure dictating the barrier and transport properties of the leaf cuticle. It is a significant imaging challenge to analyse the very thin and often complex wax-like leaf cuticle morphology in their natural state. Scanning electron microscopy (SEM) and to a lesser extent Atomic force microscopy are techniques that have been used to study the leaf surface but their remains information that is difficult to obtain via these approaches. SEM is able to produce highly detailed and high-resolution images needed to study leaf structures at the submicron level. It typically operates in a vacuum or low pressure environment and as a consequence is generally unable to deal with the in situ analysis of dynamic surface events at submicron scales. Atomic force microscopy also possess the high-resolution imaging required and can follow dynamic events in ambient and liquid environments, but can over exaggerate small features and cannot image most leaf surfaces due to their inherent roughness at the micron scale. Scanning ion conductance microscopy (SICM), which operates in a liquid environment, provides a potential complementary analytical approach able to address these issues and which is yet to be explored for studying leaf surfaces. Here we illustrate the potential of SICM on various leaf surfaces and compare the data to SEM and atomic force microscopy images on the same samples. In achieving successful imaging we also show that SICM can be used to study the wetting of hydrophobic surfaces in situ. This has potentially wider implications than the study of leaves alone as surface wetting phenomena are important in a range of fundamental and applied studies

Multiboronic acid-conjugated chitosan scaffolds with glucose selectivity to insulin release

The principal challenge for the use of boronic acids (BA) as glucose sensors is their lack of specificity for glucose. We examined the selectivity of and insulin release from two boronic acids- (2-formyl-3-thienylboronic acid (FTBA) and 4-formylphenylboronic acid (FPBA)) conjugated chitosan scaffolds to glucose and fructose. Adsorption of glucose to BA: chitosan conjugates was dose-dependent up to 1:1 at 35 and 42% for FPBA and FTBA respectively but the FTBA conjugates adsorbed more glucose and fructose at respective FPBA ratios. The affinity of both BA conjugates to glucose decreased with increase in BA ratio. On the other hand, the affinity of both BA conjugates for fructose decreased from ratio 1:1 to 2:1 then rose again at 3:1. Insulin release from FPBA nanoparticles (FPBAINP) and FTBA nanoparticles (FTBAINP) were both concentration-dependent within glyceamically relevant values (1–3 mg/ml glucose and 0.002 mg/ml fructose). Furthermore, the total amounts of insulin released from FPBAINP in both the media were higher than from FTBAINP. Both FPBAINP and FTBAINP have the potential for development as a glucose-selective insulin delivery system in physiological settings

On bromine, nitrogen oxides and ozone depletion in the tropospheric plume of Erebus volcano (Antarctica)

International audienceSince the discovery of bromine oxide (BrO) in volcanic emissions, there has been speculation concerning its role in chemical evolution and notably ozone depletion in volcanic plumes. We report the first measurements using Differential Optical Absorption Spectroscopy (DOAS) of BrO in the tropospheric plume of the persistently degassing Erebus volcano (Antarctica). These are the first observations pertaining to emissions from an alkaline phonolitic magma. The observed BrO/SO2 ratio of 2.5 x 10-4 is similar to that measured at andesitic arc volcanoes. The high abundance of BrO is consistent with high abundances of F and Cl relative to sulfur in the Erebus plume. Our estimations of HBr flux and BrO production rate suggest that reactive bromine chemistry can explain a 35% loss of tropospheric O3 observed in the Erebus plume at approximately 30 km from source (Oppenheimer et al., 2010). Erebus also has a permanent lava lake, which could result in generation of NOx by thermal fixation of atmospheric N2 at the hot lava surface. Any NOx emission could play a potent role in reactive bromine chemistry. However, the presence of NO2 could not be detected in the plume, about 400 m above the lake, in our DOAS observations of 2005. Nor could we reproduce spectroscopic retrievals that reportedly identified NO2 in DOAS observations from 2003 made of the Erebus plume (Oppenheimer et al., 2005). Based on the NO2 detection limit of our analysis, we can state an upper limit of the NO2/SO2 ratio of ≤ 0.012, an order of magnitude lower than previously reported. Our new result supports a rapid oxidation of NOx in the young plume and is more consistent with measurements of NOy species measured using an instrumented aircraft flying in the plume. Model simulations, tuned for Erebus, were performed to reproduce the BrO/SO2 observed in the young plume and to investigate the impact of NOx emissions at source on the subsequent formation of BrO in the plume. They support our hypothesis of rapid conversion of NOx to NOy in the vicinity of the lava lake. This study thus places new constraints on the interaction between reactive nitrogen and bromine species in volcanic plumes, and its effects on ozone

Controlling the release of indomethacin from glass solutions layered with a rate controlling membrane using fluid-bed processing. Part 1: Surface and cross-sectional chemical analysis

Fluid bed coating has been shown to be a suitable manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug–polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In this study, fluid bed coating is proposed for the production of controlled release dosage forms of glass solutions by applying a second, rate controlling membrane on top of the glass solution. Adding a second coating layer adds to the physical and chemical complexity of the drug delivery system, so a thorough understanding of the physical structure and phase behavior of the different coating layers is needed. This study aimed to investigate the surface and cross-sectional characteristics (employing scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (ToF-SIMS)) of an indomethacin–polyvinylpyrrolidone (PVP) glass solution, top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) were also considered. In addition, polymer miscibility and the phase analysis of the underlying glass solution were investigated. Significant differences in surface and cross-sectional topography of the different rate controlling membranes or the way they are applied (solution vs dispersion) were observed. These observations can be linked to the polymer miscibility differences. The presence of PVP was observed in all rate controlling membranes, even if it is not part of the coating solution. This could be attributed to residual powder presence in the coating chamber. The distribution of PVP among the sample surfaces depends on the concentration and the rate controlling polymer used. Differences can again be linked to polymer miscibility. Finally, it was shown that the underlying glass solution layer remains amorphous after coating of the rate controlling membrane, whether formed from an ethanol solution or an aqueous dispersion

Study of NAP adsorption and assembly on the surface of HOPG

NAP is an octapeptide that has demonstrated a neuroprotective/therapeutic efficacy at very low concentrations in preclinical studies and in a number of clinical trials. Yet little is known about its structural organization at low concentrations. Here, we have employed atomic force microscopy to investigate NAP peptide assembly on graphite in aqueous media at nanomolar concentration. High spatial resolution scans of NAP assemblies reveal their fine structure with clearly resolved single NAP units. This observation leads us to conclude that NAP molecules do not form complex self-assembled structures at nanomolar concentration when adsorbed on graphite surface

The snomipede : a parallel platform for scanning near-field photolithography.

Using scanning near-field lithography (SNP), it is possible to pattern molecules at surfaces with a resolution as good as 9 nm [M. Montague, R. E. Ducker, K. S. L. Chong, R. J. Manning, F. J. M. Rutten, M. C. Davies and G. J. Leggett, Langmuir 23 (13), 7328–7337 (2007)]. However, in common with other scanning probe techniques, SNP has previously been considered a serial process, hindering its use in many applications. IBM’s “Millipede” addresses this problem by utilizing an array of local probes operating in parallel. Here, we describe the construction of two instruments (Snomipedes) that integrate near-field optical methods into the parallel probe paradigm and promise the integration of top–down and bottom–up fabrication methods over macroscopic areas. Both are capable of performing near-field lithography with 16 probes in parallel spanning approximately 2 mm. The instruments can work in both ambient and liquid environments, key to many applications in nanobiology. In both, separate control of writing is possible for each probe. We demonstrate the deprotection of self-assembled monolayers of alkylsilanes with photocleavable protecting groups and subsequent growth of nanostructured polymer brushes from these nanopatterned surfaces by atom-transfer radical polymerization

Imaging of crystalline and amorphous surface regions using time-of-flight secondary-ion mass spectrometry (ToF-SIMS): application to pharmaceutical materials

The structure of a material, in particular the extremes of crystalline and amorphous forms, significantly impacts material performance in numerous sectors such as semiconductors, energy storage, and pharmaceutical products, which are investigated in this paper. To characterize the spatial distribution for crystalline−amorphous forms at the uppermost molecular surface layer, we performed time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) measurements for quench-cooled amorphous and recrystallized samples of the drugs indomethacin, felodipine, and acetaminophen. Polarized light microscopy was used to localize crystallinity induced in the samples under controlled conditions. Principal component analysis was used to identify the subtle changes in the ToF-SIMS spectra indicative of the amorphous and crystalline forms for each drug. The indicators of amorphous and crystalline surfaces were common in type across the three drugs, and could be explained in general terms of crystal packing and intermolecular bonding, leading to intramolecular chain scission in the formation of secondary ions. Less intramolecular scission occurred in the amorphous form, resulting in a greater intensity of molecular and dimer secondary ions. To test the generality of amorphous−crystalline differentiation using ToF-SIMS, a different recrystallization method was investigated where acetaminophen single crystals were recrystallized from supersaturated solutions. The findings indicated that the ability to assign the crystalline/amorphous state of the sample using ToF-SIMS was insensitive to the recrystallization method. This demonstrates ToF-SIMS capabilities of detecting and mapping ordered crystalline and disordered amorphous molecular materials forms at micron spatial resolution in the uppermost surface of a material