Thermodynamic and kinetic properties of interpolymer complexes assessed by isothermal titration calorimetry and surface plasmon resonance

Interpolymer complexes (IPCs) formed between complimentary polymers in solution have shown a wide range of applications from drug delivery to biosensors. This work describes the combined use of isothermal titration calorimetry and surface plasmon resonance to investigate the thermodynamic and kinetic processes during hydrogen-bonded interpolymer complexation. Varied polymers that are commonly used in layer-by-layer coatings and pharmaceutical preparations were selected to span a range of chemical functionalities including some known IPCs previously characterized by other techniques, and other polymer combinations with unknown outcomes. This work is the first to comprehensively detail the thermodynamic and kinetic data of hydrogen bonded IPCs, aiding understanding and detailed characterization of the complexes. The applicability of the two techniques in determining thermodynamic, gravimetric and kinetic properties of IPCs is considered.

On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase.

A carbamazepine-indomethacin (1 : 1) cocrystal produced by milling

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1 : 1 cocrystal, whose structure has been determined from laboratory powder X-ray diffraction (PXRD) data

A pilot study investigating the effects of a single dose of a flavonoid-rich blueberry drink on memory in 8-10 year old children

Recent evidence from animal and adult human subjects has demonstrated potential benefits to cognition from flavonoid supplementation. This study aimed to investigate whether these cognitive benefits extended to a sample of school-aged children. Using a cross-over design, with a wash out of at least seven days between drinks, fourteen 8-10 year old children consumed either a flavonoid-rich blueberry drink or matched vehicle. Two hours after consumption, subjects completed a battery of five cognitive tests comprising the Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and a Visual N-back. In comparison to vehicle, the blueberry drink produced significant improvements in the delayed recall of a previously learned list of words, showing for the first time a cognitive benefit for acute flavonoid intervention in children. However, performance on a measure of proactive interference indicated that the blueberry intervention led to a greater negative impact of previously memorised words on the encoding of a set of new words. There was no benefit of our blueberry intervention for measures of attention, response inhibition or visuo-spatial memory. While findings are mixed, the improvements in delayed recall found in this pilot study suggest that, following acute flavonoid-rich blueberry interventions, school aged children encode memory items more effectively.

Time-varying price discovery in the eighteenth century: empirical evidence from the London and Amsterdam stock markets

This paper examines the time-varying nature of price discovery in eighteenth century cross-listed stocks. Specifically, we investigate how quickly news is reflected in prices for two of the great moneyed com- panies, the Bank of England and the East India Company, over the period 1723 to 1794. These British companies were cross-listed on the London and Amsterdam stock exchange and news between the capitals flowed mainly via the use of boats that transported mail. We examine in detail the historical context sur- rounding the defining events of the period, and use these as a guide to how the data should be analysed. We show that both trading venues contributed to price discovery, and although the London venue was more important for these stocks, its importance varies over time.

Propagation of the Madden–Julian Oscillation and scale interaction with the diurnal cycle in a high-resolution GCM

The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak.

Acrylamide in potato crisps prepared from 20 UK-grown varieties: effects of variety and tuber storage time

Twenty varieties of field-grown potato were stored for 2 months and 6 months at 8 °C. Mean acrylamide contents in crisps prepared from all varieties at both storage times ranged from 131 μg per kg in Verdi to 5360 μg per kg in Pentland Dell. In contrast to previous studies, the longer storage period did not affect acrylamide formation significantly for most varieties, the exceptions being Innovator, where acrylamide formation increased, and Saturna, where it decreased. Four of the five varieties designated as suitable for crisping produced crisps with acrylamide levels below the European Commission indicative value of 1000 μg per kg (Saturna, Lady Rosetta, Lady Claire, and Verdi); the exception was Hermes. Two varieties more often used for French fries, Markies and Fontane, also produced crisps with less than 1000 μg per kg acrylamide. Correlations between acrylamide, its precursors and crisp colour are described, and the implications of the results for production of potato crisps are discussed.

The greening of Arabia: multiple opportunities for human occupation of the Arabian peninsula during the Late Pleistocene inferred from an ensemble of climate model simulations

Climate models are potentially useful tools for addressing human dispersals and demographic change. The Arabian Peninsula is becoming increasingly significant in the story of human dispersals out of Africa during the Late Pleistocene. Although characterised largely by arid environments today, emerging climate records indicate that the peninsula was wetter many times in the past, suggesting that the region may have been inhabited considerably more than hitherto thought. Explaining the origins and spatial distribution of increased rainfall is challenging because palaeoenvironmental research in the region is in an early developmental stage. We address environmental oscillations by assembling and analysing an ensemble of five global climate models (CCSM3, COSMOS, HadCM3, KCM, and NorESM). We focus on precipitation, as the variable is key for the development of lakes, rivers and savannas. The climate models generated here were compared with published palaeoenvironmental data such as palaeolakes, speleothems and alluvial fan records as a means of validation. All five models showed, to varying degrees, that the Arabia Peninsula was significantly wetter than today during the Last Interglacial (130 ka and 126/125 ka timeslices), and that the main source of increased rainfall was from the North African summer monsoon rather than the Indian Ocean monsoon or from Mediterranean climate patterns. Where available, 104 ka (MIS 5c), 56 ka (early MIS 3) and 21 ka (LGM) timeslices showed rainfall was present but not as extensive as during the Last Interglacial. The results favour the hypothesis that humans potentially moved out of Africa and into Arabia on multiple occasions during pluvial phases of the Late Pleistocene.

Using virtual environments for trigger identification in addiction treatment

This paper presents a novel application of virtual environments to assist in encouraging behavior change in individuals who misuse drugs or alcohol. We describe the user-centered design of a series of scenes to engage users in the identification of triggers and to encourage discussions about relevant coping skills. Results from the initial testing of this application with six service users showed variation in user responses. Results also suggested that the system should encourage group discussion and that it was linked to a small improvement in users’ confidence in understanding and identifying triggers.

Assessing the ability of rural agrarian areas to provide Cultural Ecosystem Services (CES): a Multi Scale Social Indicator Framework (MSIF)

Assessing the ways in which rural agrarian areas provide Cultural Ecosystem Services (CES) is proving difficult to achieve. This research has developed an innovative methodological approach named as Multi Scale Indicator Framework (MSIF) for capturing the CES embedded into the rural agrarian areas. This framework reconciles a literature review with a trans-disciplinary participatory workshop. Both of these sources reveal that societal preferences diverge upon judgemental criteria which in turn relate to different visual concepts that can be drawn from analysing attributes, elements, features and characteristics of rural areas. We contend that it is now possible to list a group of possible multi scale indicators for stewardship, diversity and aesthetics. These results might also be of use for improving any existing European indicators frameworks by also including CES. This research carries major implications for policy at different levels of governance, as it makes possible to target and monitor policy instruments to the physical rural settings so that cultural dimensions are adequately considered. There is still work to be developed on regional specific values and thresholds for each criteria and its indicator set. In practical terms, by developing the conceptual design within a common framework as described in this paper, a considerable step forward towards the inclusion of the cultural dimension in European wide assessments can be made.

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays.

Le credit au Moyen Age: les prets a la couronne D'Angleterre entre 1272 et 1345

A summary of some of the key findings of a recent ESRC-funded project based at the ICMA centre, University of Reading. This study applied modern financial analysis and theories to the early history of sovereign debt, in this case the credit arrangements between the ‘Three Edwards’, kings of England 1272-1377, and a succession of Italian merchant societies.