Targeted mass spectrometry methods for detecting oxidative post-translational modifications

Oxidative post-translational modifications (oxPTMs) can alter the function of proteins, and are important in the redox regulation of cell behaviour. The most informative technique to detect and locate oxPTMs within proteins is mass spectrometry (MS). However, proteomic MS data are usually searched against theoretical databases using statistical search engines, and the occurrence of unspecified or multiple modifications, or other unexpected features, can lead to failure to detect the modifications and erroneous identifications of oxPTMs. We have developed a new approach for mining data from accurate mass instruments that allows multiple modifications to be examined. Accurate mass extracted ion chromatograms (XIC) for specific reporter ions from peptides containing oxPTMs were generated from standard LC-MSMS data acquired on a rapid-scanning high-resolution mass spectrometer (ABSciex 5600 Triple TOF). The method was tested using proteins from human plasma or isolated LDL. A variety of modifications including chlorotyrosine, nitrotyrosine, kynurenine, oxidation of lysine, and oxidized phospholipid adducts were detected. For example, the use of a reporter ion at 184.074 Da/e, corresponding to phosphocholine, was used to identify for the first time intact oxidized phosphatidylcholine adducts on LDL. In all cases the modifications were confirmed by manual sequencing. ApoB-100 containing oxidized lipid adducts was detected even in healthy human samples, as well as LDL from patients with chronic kidney disease. The accurate mass XIC method gave a lower false positive rate than normal database searching using statistical search engines, and identified more oxidatively modified peptides. A major advantage was that additional modifications could be searched after data collection, and multiple modifications on a single peptide identified. The oxPTMs present on albumin and ApoB-100 have potential as indicators of oxidative damage in ageing or inflammatory diseases.

The 'voice' approach of trade associations:support for SMEs accessing a research institute

Access to external sources of technical knowledge is one of the keys to staying innovative for small and medium-sized enterprises (SMEs). The literature suggests that SMEs with a weak internal R&D capacity do not make much use of institutional sources like research institutes and universities. In this paper I investigate how trade associations can induce member SMEs to use a research institute. The case of a public research institute and SMEs in the textile industry in Kyoto, Japan is examined. Evidence from the case suggests that trade associations facilitate the use of the institute by expressing a collective `voice' to the management of the institute. The effect is evident among active members in the use of services involving a large information gap as to their benefits. I also consider a shortcoming of the collective approach and suggest some measures to be taken on the part of research institutes.

Supporting English language teachers doing further degrees at a distance:a web based strategy researched

This thesis explores how the world-wide-web can be used to support English language teachers doing further studies at a distance. The future of education worldwide is moving towards a requirement that we, as teacher educators, use the latest web technology not as a gambit, but as a viable tool to improve learning. By examining the literature on knowledge, teacher education and web training, a model of teacher knowledge development, along with statements of advice for web developers based upon the model are developed. Next, the applicability and viability of both the model and statements of advice are examined by developing a teacher support site (bttp://www. philseflsupport. com) according to these principles. The data collected from one focus group of users from sixteen different countries, all studying on the same distance Masters programme, is then analysed in depth. The outcomes from the research are threefold: A functioning website that is averaging around 15, 000 hits a month provides a professional contribution. An expanded model of teacher knowledge development that is based upon five theoretical principles that reflect the ever-expanding cyclical nature of teacher learning provides an academic contribution. A series of six statements of advice for developers of teacher support sites. These statements are grounded in the theoretical principles behind the model of teacher knowledge development and incorporate nine keys to effective web facilitation. Taken together, they provide a forward-looking contribution to the praxis of web supported teacher education, and thus to the potential dissemination of the research presented here. The research has succeeded in reducing the proliferation of terminology in teacher knowledge into a succinct model of teacher knowledge development. The model may now be used to further our understanding of how teachers learn and develop as other research builds upon the individual study here. NB: Appendix 4 is only available only available for consultation at Aston University Library with prior arrangement.

Finding qualitative research: an evaluation of search strategies

Background Qualitative research makes an important contribution to our understanding of health and healthcare. However, qualitative evidence can be difficult to search for and identify, and the effectiveness of different types of search strategies is unknown. Methods Three search strategies for qualitative research in the example area of support for breast-feeding were evaluated using six electronic bibliographic databases. The strategies were based on using thesaurus terms, free-text terms and broad-based terms. These strategies were combined with recognised search terms for support for breast-feeding previously used in a Cochrane review. For each strategy, we evaluated the recall (potentially relevant records found) and precision (actually relevant records found). Results A total yield of 7420 potentially relevant records was retrieved by the three strategies combined. Of these, 262 were judged relevant. Using one strategy alone would miss relevant records. The broad-based strategy had the highest recall and the thesaurus strategy the highest precision. Precision was generally poor: 96% of records initially identified as potentially relevant were deemed irrelevant. Searching for qualitative research involves trade-offs between recall and precision. Conclusions These findings confirm that strategies that attempt to maximise the number of potentially relevant records found are likely to result in a large number of false positives. The findings also suggest that a range of search terms is required to optimise searching for qualitative evidence. This underlines the problems of current methods for indexing qualitative research in bibliographic databases and indicates where improvements need to be made.

Can your vendor innovate for you?

Professor Ilan Oshri of Loughborough University’s Centre for Global Sourcing and Services and Professor Julia Kotlarsky look at the challenges of partnering with vendors on innovation programmes. What are the keys to a successful relationship?

Is there a role for telemedicine in adult allergy services?

Telemedicine refers to the application of telecommunication and information technology (IT) in the delivery of health and clinical care at a distance or remotely and can be broadly considered in two modalities: store-and-forward and real-time interactive services. Preliminary studies have shown promising results in radiology, dermatology, intensive care, diabetes, rheumatology and primary care. However, the evidence is limited and hampered by small sample sizes, paucity of randomised controlled studies and lack of data relating to cost-effectiveness, health related quality of life and patient and clinician satisfaction. This review appraises the evidence from studies that have employed telemedicine tools in other disciplines and makes suggestions for its potential applications in specific clinical scenarios in adult allergy services. Possible examples include: triaging patients to determine the need for allergy tests; pre-assessment for specialised treatments such as allergen immunotherapy; follow up to assess treatment response and side effects; and education in self-management plan including training updates for self-injectable adrenaline and nasal spray use. This approach might improve access for those with limited mobility or living far away from regional centres, as well as bringing convenience and cost savings for the patient and service provider. These potential benefits need to be carefully weighed against evidence of service safety and quality. Keys to success include delineation of appropriate clinical scenarios, patient selection, training, IT support and robust information governance framework. Well-designed prospective studies are needed to evaluate its role. This article is protected by copyright. All rights reserved.

Non-Western small states:activists or survivors?

In this introduction to the collection, we explain its focus on non-Western small states. While the terms ‘non-Western’ and ‘small states’ are problematic – we discuss these problems here – the smallness and non-Westerness of the states studied by the contributing authors set them apart in a way that has attracted little academic attention so far. They allow them to operate with fewer normative and practical constraints than their bigger, Western counterparts; offer them a wide range of (often historically forged) political ties; and force them to draw on a diversity of approaches and strategic thinking, and a creativity, that they are too rarely credited for. Non-Western small states, rather than being mere survivors constrained to the world’s periphery, are better understood as activist states intent on existing. The collection offers a range of analytical keys to make sense of these states and their role in the international scene.

Simultaneous optimization of colloidal stability and interfacial charge transfer efficiency in photocatalytic Pt/CdS nanocrystals

Colloidal stability and efficient interfacial charge transfer in semiconductor nanocrystals are of great importance for photocatalytic applications in aqueous solution since they provide long-term functionality and high photocatalytic activity, respectively. However, colloidal stability and interfacial charge transfer efficiency are difficult to optimize simultaneously since the ligand layer often acts as both a shell stabilizing the nanocrystals in colloidal suspension and a barrier reducing the efficiency of interfacial charge transfer. Here, we show that, for cysteine-coated, Pt-decorated CdS nanocrystals and Na2SO3 as hole scavenger, triethanolamine (TEOA) replaces the original cysteine ligands in situ and prolongs the highly efficient and steady H2 evolution period by more than a factor of 10. It is shown that Na2SO3 is consumed during H2 generation while TEOA makes no significant contribution to the H2 generation. An apparent quantum yield of 31.5%, a turnover frequency of 0.11 H2/Pt/s, and an interfacial charge transfer rate faster than 0.3 ps were achieved in the TEOA stabilized system. The short length, branched structure and weak binding of TEOA to CdS as well as sufficient free TEOA in the solution are the keys to enhancing colloidal stability and maintaining efficient interfacial charge transfer at the same time. Additionally, TEOA is commercially available and cheap, and we anticipate that this approach can be widely applied in many photocatalytic applications involving colloidal nanocrystals.

The implementation of a functional query language front-end to a relational database system. Available in 2 volumes.

Database systems have a user interface one of the components of which will normally be a query language which is based on a particular data model. Typically data models provide primitives to define, manipulate and query databases. Often these primitives are designed to form self-contained query languages. This thesis describes a prototype implementation of a system which allows users to specify queries against the database in a query language whose primitives are not those provided by the actual model on which the database system is based, but those provided by a different data model. The implementation chosen is the Functional Query Language Front End (FQLFE). This uses the Daplex functional data model and query language. Using FQLFE, users can specify the underlying database (based on the relational model) in terms of Daplex. Queries against this specified view can then be made in Daplex. FQLFE transforms these queries into the query language (Quel) of the underlying target database system (Ingres). The automation of part of the Daplex function definition phase is also described and its implementation discussed.

A unification-based natural language interface to a database.

An implementation of a Lexical Functional Grammar (LFG) natural language front-end to a database is presented, and its capabilities demonstrated by reference to a set of queries used in the Chat-80 system. The potential of LFG for such applications is explored. Other grammars previously used for this purpose are briefly reviewed and contrasted with LFG. The basic LFG formalism is fully described, both as to its syntax and semantics, and the deficiencies of the latter for database access application shown. Other current LFG implementations are reviewed and contrasted with the LFG implementation developed here specifically for database access. The implementation described here allows a natural language interface to a specific Prolog database to be produced from a set of grammar rule and lexical specifications in an LFG-like notation. In addition to this the interface system uses a simple database description to compile metadata about the database for later use in planning the execution of queries. Extensions to LFG's semantic component are shown to be necessary to produce a satisfactory functional analysis and semantic output for querying a database. A diverse set of natural language constructs are analysed using LFG and the derivation of Prolog queries from the F-structure output of LFG is illustrated. The functional description produced from LFG is proposed as sufficient for resolving many problems of quantification and attachment.

A critique of a model for an academic staff activity database developed to aid a department in strategic and operational decision making

This paper discusses the use of a Model developed by Aston Business School to record the work load of its academic staff. By developing a database to register annual activity in all areas of teaching, administration and research the School has created a flexible tool which can be used for facilitating both day-to-day managerial and longer term strategic decisions. This paper gives a brief outline of the Model and discusses the factors which were taken into account when setting it up. Particular attention is paid to the uses made of the Model and the problems encountered in developing it. The paper concludes with an appraisal of the Model’s impact and of additional developments which are currently being considered. Aston Business School has had a Load Model in some form for many years. The Model has, however, been refined over the past five years, so that it has developed into a form which can be used for a far greater number of purposes within the School. The Model is coordinated by a small group of academic and administrative staff, chaired by the Head of the School. This group is responsible for the annual cycle of collecting and inputting data, validating returns, carrying out analyses of the raw data, and presenting the mater ial to different sections of the School. The authors of this paper are members of this steer ing group.