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Motivated by hexagonal patterns with defects in natural and laboratory systems, we compare quantitative measures of order for nearly hexagonal, planar lattices. These include a spectral measure of order based on the Fourier transform, a geometric measure of order using the Delaunay triangulation, and topological measures of order introduced in this paper. The topological measures are based on a tool from topological data analysis called persistent homology. We contrast these measures of order by comparing their sensitivity to perturbations of Bravais lattices. We then study the imperfect hexagonal arrangements of nanodots produced by numerical simulations of partial differential equations that model the surface of a binary alloy undergoing erosion by a broad ion beam. These numerical experiments further distinguish the various measures of hexagonal order and highlight the role of various model parameters in the formation and elimination of defects. Finally, we quantify the dependence of order on prepatterning the surface to suggest experimental protocols that could lead to improved order in nanodot arrays.

BART Perks, offered by Bay Area Rapid Transit (BART) and the San Francisco County Transportation Authority (SFCTA), was a six-month test program that provided incentives to riders for traveling dur...

Thermoresponsive fluorescent nanospheres were prepared by entrapping fluorescent conjugated polymers (FCP) into biocompatible copolymerized nanospheres comprised of methacryloyloxyethyltrimethylammonium chloride and

A great deal has been written in recent years in the travel behaviour research literature about “peak travel” or “peak car”—particularly with respect to the so-called “Millennials”, young adults currently between the ages of 16 and 35. The paper reports and extends the results of longitudinal multivariate regression analysis carried out on the US National Household Travel Survey data from 1995, 2001 and 2009. The results show robust evidence for a decline in auto miles traveled between 2001 and 2009 that cannot be explained by demographic, socio-economic or land use variables or by pure trend effects. The paper then provides a discussion of whether such changes in travel behaviour over time observed from surveys could be due to changes in the survey methods or the way in which different age groups respond to specific types of surveys. There is evidence that young adults have the highest non-response bias (underreporting of trips) for diary-based surveys, but it is not clear if this bias has been growing over time. The paper closes with some suggestions for further data collection.

Calcific aortic valve disease (CAVD) is the most frequent cardiac valve pathology. Its standard treatment consists of surgical replacement either with mechanical (metal made) or biological (animal tissue made) valve prostheses, both of which have glaring deficiencies. In the search for novel materials to manufacture artificial valve tissue, we have conducted a high-throughput screening with subsequent up-scaling to identify non-degradable polymer substrates that promote valve interstitial cells (VICs) adherence/growth and, at the same time, prevent their evolution toward a pro-calcific phenotype. Here, we provide evidence that one of the two identified 'hit' polymers, poly(methoxyethylmethacrylate-co-diethylaminoethylmethacrylate), provided robust VICs adhesion and maintained the healthy VICs phenotype without inducing pro-osteogenic differentiation. This ability was also maintained when the polymer was used to coat a non-woven poly-caprolactone (PCL) scaffold using a novel solvent coating procedure, followed by bioreactor-assisted VICs seeding. Since we observed that VICs had an increased secretion of the elastin-maturing component MFAP4 in addition to other valve-specific extracellular matrix components, we conclude that valve implants constructed with this polyacrylate will drive the biological response of human valve-specific cells.

When a nominally flat surface is bombarded with a broad ion beam at oblique incidence, nanoscale ripples often develop on the surface. For high angles of incidence, surfaces typically develop into a terraced form at the late stages of their time evolution. In the present work, this process is exploited to prevent unwanted smoothing of ordered terraced substrates during the deposition of thin films. A Si surface prepatterned with a 500 nm pitch binary grating structure was bombarded at oblique incidence by a low energy Xe+ ion beam to establish an ordered terraced topography. Subsequently, Si/SiO2 bilayers were deposited on the surface, and further oblique incidence Xe+ bombardment was performed following the deposition of each Si layer to re-establish the ordered terraced topography. Self-organized processes, such as in the present work, that only require exposure of a surface to a plasma or ion source have the potential to provide a simple and inexpensive route for fabricating large-area nanostructured surfaces. The presented procedure has potential applications in the fabrication of multilayer blazed gratings for use in the extreme ultraviolet or soft x-ray regimes.

Small-molecule drugs often have limited solubility, display rapid clearance or poor selectivity that leads to undesired side-effects. Although prodrug strategies can improve solubility and lower toxicity, activation ‘on demand’ as well as targeted transport of prodrugs remains a challenge in drug delivery. Responsive polymeric nanoparticles can help meet these challenges with the encapsulation or conjugation of drugs, allowing release at the target site upon triggering by an internal or external stimulus. The adaptable design of polymeric nanoparticles allows them to play a vital role in achieving a specific and desired response following application of a specific stimulus. Here, the most recent progress in responsive polymeric nanoparticles is reviewed with a focus on the chemical properties of the utilized polymers. © 2017 Society of Chemical Industry

BackgroundWorking with people with Borderline Personality Disorder (BPD) is often viewed as challenging, especially when there is a high risk of suicide or self-harm. This study aimed to provide insight into the lived experience of clinicians working with these service users within community mental health teams.MethodUnstructured interviews were conducted with four participants from two multidisciplinary teams within the same NHS trust. Transcripts were analysed using Interpretative Phenomenological Analysis.FindingsThree superordinate themes were identified. (1) All participants emphasised the stressful nature of their role, describing its emotional impact and contributory factors, including organisational and relational issues. (2) Coping strategies were evident, which may not always have been within the participants’ awareness. (3) The task of balancing seemingly opposing possibilities was identified, paralleling the need for people with BPD to resolve dichotomous thinking.ConclusionsThere is a role for counselling psychologists in helping clinicians working within multidisciplinary teams to develop a deeper understanding of their responses through training and supervision. This could in turn enhance the care provided.

The fabrication of microarrays consisting of well-defined glycopolymers is described. This was achieved by postfunctionalization of an immobilized poly(allyl glycidyl ether) using unprotected thiol-modified carbohydrates through thiol–ene conjugation chemistry. This enabled the fabrication of glycopolymer microarrays in which the density and composition of the carbohydrate moieties varied along each of the polymer chains displayed across the array. These glycopolymer microarrays were applied in the evaluation of multivalent ligand–protein interactions with the determination of surface dissociation constants (KD) with concanavalin A and Ricinus communis agglutinin I for surface immobilized mannose-, glucose-, and galactose-containing glycopolymers and validated in solution with ITC.

Determining age structure of populations is a valuable parameter in wildlife management, but is often difficult to obtain. Here, we tested a noninvasive method via fecal DNA, hormones, and pellet morphometrics to distinguish calf from adult in Central Mountain and Boreal woodland caribou (Rangifer tarandus caribou (Gmelin, 1788)) populations. Annual surveys of fall-sampled Central Mountain caribou were done in Jasper National Park, Alberta, between 2006 and 2011 and winter-sampled Boreal caribou were surveyed in the North Interlake area, Manitoba, between 2004 and 2010. Samples were amplified at 10 microsatellite loci to identify unique individuals and capture histories were used to identify putative calves and adults. Fecal pellets were measured for length, width, depth, dry mass, and analyzed for progesterone, estrogen, and testosterone concentrations. Results showed significant differences in fecal pellet size between putative calves and adults for both sexes and populations–seasons. Progesterone concentration was significantly higher in Jasper–fall and North Interlake–winter adult females. Testosterone was significantly higher in Jasper–fall adult males. North Interlake–winter males exhibited no significant difference in hormone concentrations between age classes. When applied to the entire Jasper data set, 98% of females and 88% of males were assigned to an age class. This study illustrates the possibilities of using noninvasive methods to determine an age class in wild ungulate populations.

A flexible miniaturised multiplexed sensing optrode based on fluorescent microspheres attached to multi-core fibre is reported. Photonic measurements of pH and oxygen concentration in the distal alveolar space of a perfused ex vivo lung are performed.

Endoscopic point sensing of bacterial infections in the distal lung in vivo is challenging. Here fluorescence imaging agents are combined with time-resolved fluorescence spectroscopy to overcome limitations from tissue fluorescence by measuring the fluorescence lifetime.

Substrates for neuron culture and implantation are required to be both biocompatible and display surface compositions that support cell attachment, growth, differentiation, and neural activity. Laminin, a naturally occurring extracellular matrix protein is the most widely used substrate for neuron culture and fulfills some of these requirements, however, it is expensive, unstable (compared to synthetic materials), and prone to batch-to-batch variation. This study uses a high-throughput polymer screening approach to identify synthetic polymers that supports the in vitro culture of primary mouse cerebellar neurons. This allows the identification of materials that enable primary cell attachment with high viability even under “serum-free” conditions, with materials that support both primary cells and neural progenitor cell attachment with high levels of neuronal biomarker expression, while promoting progenitor cell maturation to neurons.

Proteases are ideal target biomarkers as they have been implicated in many disease states, including steps associated with cancer progression. Electrochemical peptide-based biosensors have attracted much interest in recent years. However, the significantly large size of the electrodes typically used in most of these platforms has led to performance limitations. These could be addressed by the enhancements offered by microelectrodes, such as rapid response times, improved mass transport, higher signal-to-noise and sensitivity, as well as more localised and less invasive measurements. We present the production and characterisation of a miniaturised electrochemical biosensor for the detection of trypsin, based on 25 μm diameter Pt microelectrodes (rather than the ubiquitous Au electrodes), benchmarked by establishing the equivalent Pt macroelectrode response in terms of quantitative response to the protease, the kinetics of cleavage and the effects of non-specific protein binding and temperature. Interestingly, although there was little difference between Au and Pt macroelectrode response, significant differences were observed between the responses of the Pt macroelectrode and microelectrode systems indicative of increased reproducibility in the microelectrode SAM structure and sensor performance between the electrodes, increased storage stability and a decrease in the cleavage rate at functionalised microelectrodes, which is mitigated by measurement at normal body temperature. Together, these results demonstrate the robustness and sensitivity of the miniaturised sensing platform and its ability to operate within the clinically-relevant concentration ranges of proteases in normal and disease states. These are critical features for its translation into implantable devices.

A ruthenium-based mitochondrial-targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of PtIV prodrugs into their active PtII counterparts, and drives the generation of singlet oxygen was designed. This dual mode of action drives two orthogonal cancer-cell killing mechanisms with temporal and spatial control. The designed photosensitiser was shown to elicit cell death of a panel of cancer cell lines including those showing oxaliplatin-resistance.

La couleur est bien plus que des ondes lumineuses atteignant la rétine. Dans les cercles philosophiques de l’Antiquité, elle était décrite comme le principal objectif de la vision : c’était la « peau » extérieure d’un objet, rendant celui-ci visible ou « sensible » au spectateur. Et cependant, la littérature gréco-romaine est remplie d’exemples de catégories de couleur qui ne font pas sens uniquement en termes visuels : la « mer sombre comme le vin » (oinops pontos), la peau couleur « petit-lait » (orōdēs) dans la médecine hippocratique, les visages rougissants (rubens), les cheveux couleur de miel (mellei crines), la peau de marbre des jeunes filles dans l’élégie latine, les vêtements couleur safran des orientaux décadents, les robes luxueuses de pourpre à l’odeur de poisson de la cour impériale… La couleur sollicite non seulement la vue, mais aussi l’odeur, le toucher et le goût. Le présent article développera des arguments et des idées présentées dans la monographie de l’auteur Colour and Meaning in Ancient Rome (Cambridge University Press, 2009) : dans les sociétés prémodernes comme la Grèce et Rome, les couleurs, en raison de leurs liens étroits avec des objets spécifiques et des phénomènes (plutôt que simplement des parties du spectre), étaient fréquemment des expériences synesthésiques qui avaient trait à de multiples expériences sensibles. En partant de cas particuliers, l’auteur montrera que la couleur était une expérience multi-sensorielle et que la nature de cette expérience était une préoccupation de la pensée ancienne dans plusieurs aires d’activités dans le monde gréco-romain. La compréhension de ce phénomène ne nous aide pas seulement à traduire les termes de couleurs grecs et latins. La couleur était une unité d’information sensorielle de base à travers laquelle les Anciens expérimentaient et évaluaient le monde autour d’eux. La collaboration des sens dans ces expériences invite à une approche de la perception, de la connaissance et de la compréhension qui pourrait être différente de celle employée pour le monde occidental moderne. Colour is about more than just lightwaves hitting the retina. In ancient philosophical circles, colour was described as the primary object of vision: it was the external ‘skin’ that existed at the surface of an object, and what made the object visible or ‘sensible’ to a viewer. And yet, Greco-Roman literature is riddled with examples of colour categories that do not make sense simply in visual terms: from Homer’s ‘wine-dark sea’ (oinops pontos) to ‘whey-coloured’ (orōdēs) skin in Hippocratic medicine, from blushing (rubens) faces to the honey-coloured hair (mellei crines) and marbled skin of coveted girls in Augustan elegy, and from the saffron garments of decadent easterners to the expensive fishy-smelling purple robes of the late-antique imperial court, colours appealed not just to sight, but also to smell, touch and taste. This paper will use arguments and ideas explored in my monograph Colour and Meaning in Ancient Rome (Cambridge University Press, 2009) to suggest that colours in pre-modern societies such as Greece and Rome, because of their close ties to specific objects and phenomena (rather than just parts of the spectrum), were frequently synaesthetic experiences which appealed to multiple senses and mobilized more than just eyesight. I will draw upon case studies from a range of genres and contexts to demonstrate not only that colour was a multi-sensory experience, but also that the nature of this experience was a central preoccupation of ancient thought in several areas of activity in the Greco-Roman world. An understanding of this principle, then, can do more than just help us to translate and understand difficult Greek and Latin colour terms: colour was a basic sensory unit of information through which ancients experienced and evaluated the world around them, and the collaboration of the senses in these experiences suggests an approach to perception, knowledge and understanding which could be very different from that employed in the modern west.

A rapid photo-controlled one-pot strategy for the synthesis of asymmetric star polymers was developed using two different wavelengths of light to allow spatial and temporal control of the synthesis of the star polymers with controlled structures and narrow polydispersities. Several asymmetric star structures were successfully synthesised and the simultaneous photo-induced ATRP and RAFT polymerisation was demonstrated using this procedure.

Our simulations show that dispersion can have a crucial effect on the patterns produced by oblique-incidence ion sputtering. It can lead to the formation of raised and depressed triangular regions traversed by parallel-mode ripples, and these bear a strong resemblance to nanostructures that are commonly observed in experiments. In addition, if dispersion and transverse smoothing are sufficiently strong, highly ordered ripples form. Finally, dispersion can cause the formation of protrusions and depressions that are elongated along the projected beam direction even when there is no transverse instability. This may explain why topographies of this kind form for high angles of ion incidence in cases in which ion-induced mass redistribution is believed to dominate curvature-dependent sputtering.

Three dimensional synthetic polymer scaffolds have remarkable chemical and mechanical tunability in addition to biocompatibility. However, the chemical and physical space is vast in view of the number of variables that can be altered e.g. chemical composition, porosity, pore size and mechanical properties to name but a few. Here, we report the development of an array of 3D polymer scaffolds, whereby the physical and chemical properties of the polymer substrates were controlled, characterized in parallel (e.g. micro-CT scanning of 24 samples) and biological properties screened. This approach allowed the screening of 48 different polymer scaffolds constructed in situ by means of freeze-casting and photo-polymerisation with the tunable composition and 3D architecture of the polymer scaffolds facilitating the identification of optimal 3D biomaterials. As a proof of concept, the array approach was used to identify 3D polymers that were capable of supporting cell growth while controlling their behaviour. Sitting alongside classical polymer microarray technology, this novel platform reduces the gap between the identification of a biomaterial in 2D and its subsequent 3D application.

A ruthenium-based mitochondrial-targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of Pt

Rapid in situ detection of pathogens coupled with high resolution imaging in the distal human lung has the potential to provide new insights and diagnostic utility in patients in whom pneumonia is suspected. We have previously described an antimicrobial peptide (AMP) Ubiquicidin (fragment UBI29–41) labelled with an environmentally sensitive fluorophore that optically detected bacteria in vitro but not ex vivo. Here, we describe further chemical development of this compound and demonstrate that altering the secondary structure of the AMP to generate a tri-branched dendrimeric scaffold provides enhanced signal in vitro and ex vivo and consequently allows the rapid detection of pathogens in situ in an explanted human lung. This compound (NBD-UBIdend) demonstrates bacterial labelling specificity for a broad panel of pathogenic bacteria and Aspergillus fumigatus. NBD-UBIdend demonstrated high signal-to-noise fluorescence amplification upon target engagement, did not label host mammalian cells and was non-toxic and chemically robust within the inflamed biological environment. Intrapulmonary delivery of NBD-UBIdend, coupled with optical endomicroscopy demonstrated real-time, in situ detection of bacteria in explanted whole human Cystic Fibrosis lungs.

Polymerisation reactions conducted inside cells must be compatible with the complex intracellular environment, which contains numerous molecules and functional groups that could potentially prevent or quench polymerisation reactions. Here we report a strategy for directly synthesising unnatural polymers in cells through free radical photo-polymerisation using a number of biocompatible acrylic and methacrylic monomers. This offers a platform to manipulate, track and control cellular behaviour by the in cellulo generation of macromolecules that have the ability to alter cellular motility, label cells by the generation of fluorescent polymers for long-term tracking studies, as well as the generation within cells of a variety of nanostructures. It is remarkable that free radical polymerisation chemistry can take place within such complex cellular environments and this demonstration opens up a multitude of new possibilities for how chemists can modulate cellular function and behaviour and for understanding cellular behaviour in response to the generation of free radicals.

Physiological sensing deep in tissue remains a clinical challenge. Here a flexible miniaturised sensing optrode providing a platform to perform minimally invasive in vivo in situ measurements is reported. Silica microspheres covalently coupled with a high density of ratiometrically configured fluorophores were deposited into etched pits on the distal end of a 150 µm diameter multicore optical fibre. With this platform, photonic measurements of pH and oxygen concentration with high precision in the distal alveolar space of the lung are reported. We demonstrated the phenomenon that high-density deposition of carboxyfluorescein covalently coupled to silica microspheres shows an inverse shift in fluorescence in response to varying pH. This platform delivered fast and accurate measurements (±0.02 pH units and ±0.6 mg/L of oxygen), near instantaneous response time and a flexible architecture for addition of multiple sensors.

Taking inspiration from the assembly of so-called peptoids (N-alkylglycine oligomers) we present a new synthetic methodology whereby N-heterocyclic carbene (NHC) based Pd ligands were assembled using a sub-monomer approach and loaded with Pd via solid-phase synthesis. This allowed the rapid generation a library of NHC–palladium catalysts that were readily functionalised to allow bioconjugation. These catalysts were able to rapidly activate a caged fluorophore and ‘switch-on’ an anticancer prodrug in 3D cell culture.

Polymer microarrays were utilized for the high-throughput screening and discovery of optimal polymeric substrates capable of trapping functional ratiometric fluorescence-based pH sensors. This led to the identification of poly(methyl methacrylate-co-2-(dimethylamino) ethyl acrylate) (PA101), which allowed, via dip coating, the attachment of fluorescent pH sensors onto the tips of optical fibers, resulting in robust, rapid, and reproducible sensing of physiological pHs.

The alveolar space forms the distal end of the respiratory tract where chemoreceptor driven gas exchange processes occur. In healthy humans, the physiological state within the alveoli is tightly regulated by normal homeostatic mechanisms. However, pulmonary abnormalities such as chronic obstructive pulmonary disease may induce significant perturbation of the homeostatic baselines of physiology as well as cause host tissue damage. Therefore, physiological parameters (pH, glucose, oxygen tension) within the alveolar space provide a key biomarker of innate defence. Here, we discuss an endoscope-deployable fibre-optic optrode for sensing pH in the alveolar space. In order to circumvent the unwanted Raman signal generated within the fibre, the optrode consists of a custom asymmetric dual-core optical fibre designed for spatially separated optical pump delivery and SERS signal collection. pH sensing is achieved using the surface enhanced Raman spectroscopy (SERS) signal generated from functionalised gold nanoshell sensors. We show a ~ 100-fold increase in SERS signal-to-fibre background ratio and demonstrate multiple site pH sensing in the alveoli of an ex vivo ovine lung model with a measurement accuracy of ± 0.07 pH unit.

Photoinduced electron transfer-reversible addition−fragmentation chain-transfer (PET-RAFT) polymerisation allows the controlled synthesis of polymers and provides an alternative to transition metal-based photoinitiators. Here, fluorophore-conjugated RAFT agents, containing either 5-carboxyfluorescein or a “boron-dipyrromethene” (BODIPY) moiety attached to a thiocarbonylthio group, were synthesised. Both agents enabled light-controlled (470 nm, 0.4 mW/cm2) “on/off” polymerisation yielding polymers with a Mw/Mn < 1.50. The BODIPY-based RAFT agent showed excellent photostability and gave polymers that contained a single fluorophore per polymer chain, providing an expedient route to homogeneous fluorescently labelled polymers. This agent was compatible with multiple acrylamide/acrylate monomers with a range of functional groups, with the thiocarbonylthio terminating group enabling further polymer chain extension and the formation of fluorescent block copolymers, as demonstrated by the synthesis of BODIPY-labelled poly(N,N-dimethylacrylamide)-block-poly (3-acrylamidophenyl)boronic acid).

The rational design of electrochemical methods for chiral recognition is a focus of research in the detection fields of biomolecules and pharmaceuticals. In this work, electrochemical chiral interface based on chitosan (CS) and deoxyribonucleic acid (DNA) was constructed with self-assembly technology, and then characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), cyclic voltammetry, and electrochemical impedance spectroscopy. The FT-IR and SEM results showed the spatial structure of DNA and CS changed significantly and formed superhelix structure during the self-assembly process. Differential pulse voltammetry (DPV) results showed that the oxidation peak current ratio of D-Trp to L-Trp (ID/IL) was observed to be 4.02 at 25 °C due to the synergistic effects of CS and DNA, obviously higher than that on any individual CS or DNA modified electrode. In addition, there was a linear relationship between the peak current and Trp enantiomer concentration in the range of 0.005–0.15 mM, and the detection limits of D-Trp and L-Trp were 1.33 and 1.67 µM, respectively. More importantly, the chiral interface can also be used to identify the percentage of D-Trp in non-racemic Trp enantiomers mixture solutions, showing its effectiveness and promising potential in practical applications.