Polyphosphate and pyrophosphate derivative of saccharides

The present invention provides, among other things, phosphorylated and pyrophosphate derivatives of mono-, di- and oligosaccharides, as well as structural derivatives of these compounds. These compounds have a variety of uses including for pharmaceutical applications. Also provided are methods of use in the treatment of disease, including diseases related to oxygen delivery

A review of topographic controls on moraine distribution

Ice-marginal moraines are often used to reconstruct the dimensions of former ice masses, which are then used as proxies for palaeoclimate. This approach relies on the assumption that the distribution of moraines in the modern landscape is an accurate reflection of former ice margin positions during climatically controlled periods of ice margin stability. However, the validity of this assumption is open to question, as a number of additional, nonclimatic factors are known to influence moraine distribution. This review considers the role played by topography in this process, with specific focus on moraine formation, preservation, and ease of identification (topoclimatic controls are not considered). Published literature indicates that the importance of topography in regulating moraine distribution varies spatially, temporally, and as a function of the ice mass type responsible for moraine deposition. In particular, in the case of ice sheets and ice caps ( > 1000 km2), one potentially important topographic control on where in a landscape moraines are deposited is erosional feedback, whereby subglacial erosion causes ice masses to become less extensive over successive glacial cycles. For the marine-terminating outlets of such ice masses, fjord geometry also exerts a strong control on where moraines are deposited, promoting their deposition in proximity to valley narrowings, bends, bifurcations, where basins are shallow, and/or in the vicinity of topographic bumps. Moraines formed at the margins of ice sheets and ice caps are likely to be large and readily identifiable in the modern landscape. In the case of icefields and valley glaciers (10–1000 km2), erosional feedback may well play some role in regulating where moraines are deposited, but other factors, including variations in accumulation area topography and the propensity for moraines to form at topographic pinning points, are also likely to be important. This is particularly relevant where land-terminating glaciers extend into piedmont zones (unconfined plains, adjacent to mountain ranges) where large and readily identifiable moraines can be deposited. In the case of cirque glaciers (< 10 km2), erosional feedback is less important, but factors such as topographic controls on the accumulation of redistributed snow and ice and the availability of surface debris, regulate glacier dimensions and thereby determine where moraines are deposited. In such cases, moraines are likely to be small and particularly susceptible to post-depositional modification, sometimes making them difficult to identify in the modern landscape. Based on this review, we suggest that, despite often being difficult to identify, quantify, and mitigate, topographic controls on moraine distribution should be explicitly considered when reconstructing the dimensions of palaeoglaciers and that moraines should be judiciously chosen before being used as indirect proxies for palaeoclimate (i.e., palaeoclimatic inferences should only be drawn from moraines when topographic controls on moraine distribution are considered insignificant).

Photosensitisers - the progression from photodynamic therapy to anti-infective surfaces

Introduction: The application of light as a stimulus in pharmaceutical systems and the associated ability to provide precise spatiotemporal control over location, wavelength and intensity, allowing ease of external control independent of environmental conditionals, has led to its increased use. Of particular note is the use of light with photosensitisers.

Areas covered: Photosensitisers are widely used in photodynamic therapy to cause a cidal effect towards cells on irradiation due to the generation of reactive oxygen species. These cidal effects have also been used to treat infectious diseases. The effects and benefits of photosensitisers in the treatment of such conditions are still being developed and further realised, with the design of novel delivery strategies. This review provides an overview of the realisation of the pharmaceutically relevant uses of photosensitisers, both in the context of current research and in terms of current clinical application, and looks to the future direction of research.

Expert opinion: Substantial advances have been and are being made in the use of photosensitisers. Of particular note are their antimicrobial applications, due to absence of resistance that is so frequently associated with conventional treatments. Their potency of action and the ability to immobilise to polymeric supports is opening a wide range of possibilities with great potential for use in healthcare infection prevention strategies.

Difference equation approach to two-thermocouple sensor characterization in constant velocity flow environments

Thermocouples are one of the most popular devices for temperature measurement due to their robustness, ease of manufacture and installation, and low cost. However, when used in certain harsh environments, for example, in combustion systems and engine exhausts, large wire diameters are required, and consequently the measurement bandwidth is reduced. This article discusses a software compensation technique to address the loss of high frequency fluctuations based on measurements from two thermocouples. In particular, a difference equation (DE) approach is proposed and compared with existing methods both in simulation and on experimental test rig data with constant flow velocity. It is found that the DE algorithm, combined with the use of generalized total least squares for parameter identification, provides better performance in terms of time constant estimation without any a priori assumption on the time constant ratios of the thermocouples.

Zinc selenide nano- and microspheres via microwave-assisted ionothermal synthesis

Zinc selenide nanospheres were prepared from a diphenyl diselenide precursor and a range of chloro- and bromozincate(II) ionic liquids via a microwave-assisted ionothermal route; this is the first report on the use of microwave irradiation in combination with ionic liquids to prepare this material. The method is a time-efficient and a facile one-pot reaction to produce zinc(II) selenide nanomaterials. The product formation in the ionic liquids has been monitored using Raman spectroscopy. The products have been characterised using PXRD, SEM, EDX, photoluminescence and UV-VIS spectroscopy. Advantages of this new route, such as ease of solubilisation of all reactants into one phase at high concentration, the negligible vapour pressure irrespective of the reaction temperature, very fast reaction times, ease of potential scale-up and reproducibility are discussed.

The association between glucose lowering drug use and mortality among breast cancer patients with type 2 diabetes.

This study assessed the association between glucose-lowering drug (GLD) use, including metformin, sulphonylurea derivatives and insulin, after breast cancer diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer patients, diagnosed between 1998 and 2010, with type 2 diabetes were included. Cancer information was retrieved from English cancer registries, prescription data from the UK Clinical Practice Research Datalink and mortality data from the Office of National Statistics (up to January 2012). Time-varying Cox regression models were used to calculate HRs and 95 % CIs for the association between GLD use and breast cancer-specific and all-cause mortality. In 1057 patients with diabetes before breast cancer, there was some evidence that breast cancer-specific mortality decreased with each year of metformin use (adjusted HR 0.88; 95 % CI 0.75–1.04), with a strong association seen with over 2 years of use (adjusted HR 0.47; 95 % CI 0.26–0.82). Sulphonylurea derivative use for less than 2 years was associated with increased breast cancer-specific mortality (adjusted HR 1.70; 95 % CI 1.18–2.46), but longer use was not (adjusted HR 0.94; 95 % CI 0.54–1.66). In 706 patients who developed diabetes after breast cancer, similar patterns were seen for metformin, but sulphonylurea derivative use was strongly associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16–6.16), with similar estimates for short- and long-term users. This study provides some support for an inverse association between, mainly long-term, metformin use and (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was associated with increased breast cancer-specific mortality, but this should be interpreted cautiously, as it could reflect selective prescribing in advanced cancer patients.

Breaking the Intimate Screen: Pre-Recording, Special Effects and the Aesthetics of Early British Television

The technological constraints of early British television encouraged drama productions which emphasised the immediate, the enclosed and the close-up, an approach which Jason Jacobs described in the title of his seminal study as 'the intimate screen'. While Jacobs' book showed that this conception of early British television drama was only part of the reality, he did not focus on the role that special effects played in expanding the scope of the early television screen. This article will focus upon this role, showing that special effects were not only of use in expanding the temporal and spatial scope of television, but were also considered to be of interest to the audience as a way of exploring the new medium, receiving coverage in the popular press. These effects included pre-recorded film inserts, pre-recorded narration, multiple sets, model work and animation, combined with the live studio performances. Drawing upon archival research into television production files and scripts as well as audience responses and periodical coverage of television at the time of broadcast, this article will focus on telefantasy. This genre offered particular opportunities for utilising effects in ways that seemed appropriate for the experimentation with the form of television and for the drama narratives. This period also saw a variety of shifts within television as the BBC sought to determine a specific identity and understand the possibilities for the new medium.
This research also incorporates the BBC's own research and internal dialogue concerning audiences and how their tastes should best be met, at a time when the television audience was not only growing in terms of number but was also expanding geographically and socially beyond the moneyed Londoners who could afford the first television sets and were within range of the Alexandra Palace transmissions. The primary case study for this article will be the 1949 production of H.G.Wells’ The Time Machine, which incorporated pre-recorded audio and film inserts, which expanded the narrative out of the live studio performance both temporally and spatially, with the effects work receiving coverage in the popular magazine Illustrated. Other productions considered will be the 1938 and 1948 productions of RUR, the 1948 production of Blithe Spirit, and the 1950 adaptation of The Strange Case of Dr Jekyll and Mr Hyde. Despite the focus on telefantasy, this article will also include examples from other genres, both dramatic and factual, showing how the BBC's response to the changing television audience was to restrict drama to a more 'realistic' aesthetic and to move experimentation with televisual form to non-drama productions such as variety performances.

Stout: Cloudy's Atomic and Molecular Database

We describe a new atomic and molecular database we developed for use in the spectral synthesis code Cloudy. The design of Stout is driven by the data needs of Cloudy, which simulates molecular, atomic, and ionized gas with kinetic temperatures and densities spanning the low-to high-density limits. The radiation field between photon energies 10−8 Ry and 100 MeV is considered, along with all atoms and ions of the lightest 30 elements, and ~102 molecules. For ease of maintenance, the data are stored in a format as close as possible to the original data sources. Few data sources include the full range of data we need. We describe how we fill in the gaps in the data or extrapolate rates beyond their tabulated range. We tabulate data sources both for the atomic spectroscopic parameters and for collision data for the next release of Cloudy. This is not intended as a review of the current status of atomic data, but rather a description of the features of the database which we will build upon.

Identification of Dynamics of Surface Suction Over an Airfoil at Low Reynolds Numbers

This paper deals with identification of dynamics in suction control of airfoils for low Reynolds number regimes (8 x 10^4 - 5 x 10^5). In particular, the dynamics of interest is the map that relates suction pressure and surface pressure. Identification of such dynamics is of use to a variety of active control applications including suction control in small/medium wind turbines which operate in these Reynolds number regimes. Prior research has largely focused on higher Reynolds number regimes, creating a need for such a study. Towards identifying the said dynamic relations, experiments were conducted on NACA0012 airfoil in a wind tunnel. The dynamic relation between suction and surface pressure was identified as an overdamped second order system.

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.