Town centre improvements through sustainable procurement

The project is investigating the potential to reduce town centre business costs and negative environmental impacts through the use of innovations in procurement and freight transport. These innovations include collaborative procurement, Business Improvement Districts, and Delivery and Servicing Plans. These approaches were being trialled and evaluated in three British towns: Cambridge, Lowestoft and Norwich. 17 companies were developing and applying a Delivery and Servicing Plan. Transport reduction effects were achieved

On Two Babylonian Kings

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The Impact of Open Access on Teaching—How Far Have We Come?

This article seeks to understand how far the United Kingdom higher education (UK HE) sector has progressed towards open access (OA) availability of the scholarly literature it requires to support courses of study. It uses Google Scholar, Unpaywall and Open Access Button to identify OA copies of a random sample of articles copied under the Copyright Licensing Agency (CLA) HE Licence to support teaching. The quantitative data analysis is combined with interviews of, and a workshop with, HE practitioners to investigate four research questions. Firstly, what is the nature of the content being used to support courses of study? Secondly, do UK HE establishments regularly incorporate searches for open access availability into their acquisition processes to support teaching? Thirdly, what proportion of content used under the CLA Licence is also available on open access and appropriately licenced? Finally, what percentage of content used by UK HEIs under the CLA Licence is written by academics and thus has the potential for being made open access had there been support in place to enable this? Key findings include the fact that no interviewees incorporated OA searches into their acquisitions processes. Overall, 38% of articles required to support teaching were available as OA in some form but only 7% had a findable re-use licence; just 3% had licences that specifically permitted inclusion in an ‘electronic course-pack’. Eighty-nine percent of journal content was written by academics (34% by UK-based academics). Of these, 58% were written since 2000 and thus could arguably have been made available openly had academics been supported to do so

Targeted activation of toll-like receptors: conjugation of a toll-like receptor 7 agonist to a monoclonal antibody maintains antigen binding and specificity

Therapeutic activation of Toll-like receptors (TLR) has potential for cancer immunotherapy, for augmenting the activity of anti-tumor monoclonal antibodies (mAbs), and for improved vaccine adjuvants. A previous attempt to specifically target TLR agonists to dendritic cells (DC) using mAbs failed because conjugation led to non-specific binding and mAbs lost specificity. We demonstrate here for the first time the successful conjugation of a small molecule TLR7 agonist to an anti-tumour mAb (the anti-hCD 20 rituximab) without compromising antigen specificity. The TLR7 agonist UC-1V150 was conjugated to rituximab using two conjugation methods and yield, molecular substitution ratio, retention of TLR7 activity and specificity of antigen binding were compared. Both conjugation methods produced rituximab-UC-1V150 conjugates with UC-1V150 : rituximab ratio ranging from 1:1 to 3:1 with drug loading quantified by UV spectroscopy and drug substitution ratio verified by MALDI TOF mass spectroscopy. The yield of purified conjugates varied with conjugation method, and dropped as low as 31% using a method previously described for conjugating UC-1V150 to proteins, where a bifunctional crosslinker was firstly reacted with rituximab, and secondly to the TLR7 agonist. We therefore developed a direct conjugation method by producing an amine-reactive UV active version of UC-1V150, termed NHS:UC-1V150. Direct conjugation with NHS:UC-1V150 was quick and simple and gave improved conjugate yields of 65-78%. Rituximab-UC-1V150 conjugates had the expected pro-inflammatory activity in vitro (EC50 28-53 nM) with a significantly increased activity over unconjugated UC-1V150 (EC50 547 nM). Antigen binding and specificity of the rituxuimab-UC-1V150 conjugates was retained, and after incubation with human peripheral blood leukocytes, all conjugates bound strongly only to CD20-expressing B cells whilst no non-specific binding to CD20-negative cells was observed. Selective targeting of Toll-like receptor activation directly within tumors or to DC is now feasible

Influence of metals and metalloids on the composition and fluorescence quenching of the extracellular polymeric substances produced by the polymorphic fungus <i>Aureobasidium pullulans</i>

Aureobasidium pullulansis a ubiquitous and widely distributed fungus in the environment, and exhibits substantial tolerance against toxic metals. However, the interactions between metals and metalloids with the copious extracellular polymeric substances (EPS) produced byA. pullulansand possible relationships to tolerance are not well understood. In this study, it was found that mercury (Hg) and selenium (Se), as selenite, not only significantly inhibited growth ofA. pullulansbut also affected the composition of produced EPS. Lead (Pb) showed little influence on EPS yield or composition. The interactions of EPS fromA. pullulanswith the tested metals and metalloids depended on the specific element and their concentration. Fluorescence intensity measurements of the EPS showed that the presence of metal(loid)s stimulated the production of extracellular tryptophan-like and aromatic protein-like substances. Examination of fluorescence quenching and calculation of binding constants revealed that the fluorescence quenching process for Hg; arsenic (As), as arsenite; and Pb to EPS were mainly governed by static quenching which resulted in the formation of a stable non-fluorescent complexes between the EPS and metal(loid)s. Se showed no significant interaction with the EPS according to fluorescence quenching. These results provide further understanding of the interactions between metals and metalloids and EPS produced by fungi and their contribution to metal(loid) tolerance

Biology and population studies of two endemic Nematoceras (orchid) species on sub-Antarctic Macquarie Island

Two endemic orchid species, Nematoceras dienemum and N. sulcatum, are known from sub-Antarctic Macquarie Island. Several additional orchid populations on the island are reported and deistogamy is documented in N. dienemum for the first time. The known population sizes, habitats and locations for both orchid species are documented here, and new information on their biology and population ecology is provided

Microprocessor system to recover data from a self-scanning photodiode array

A microprocessor system developed at Lawrence Livermore Laboratory has expedited the recovery of data describing the low energy x-ray spectra radiated by laser-fusion targets. An Intel microprocessor controls the digitization and scanning of the data stream of an x-ray-sensitive self-scanning photodiode array incorporated in a crystal diffraction spectrometer. (auth