Epitope mapping the specific residues of an antibody/antigen interaction can be used to support mechanistic interpretation, antibody optimization, and epitope novelty assessment. Thus, there is a strong need for mapping methods, particularly integrative ones. Here we report identification of an energetic epitope by determining the interfacial hot-spot that dominates the binding affinity for an anti-IL-23 antibody by using the complementary approaches of hydrogen/deuterium exchange mass spectrometry (HDX-MS), fast photochemical oxidation of proteins (FPOP), alanine shave mutagenesis, and binding analytics. Five peptide regions on IL-23 with reduced backbone amide solvent accessibility upon antibody binding were identified by HDX-MS, and five different peptides over the same three regions were identified by FPOP. In addition, FPOP analysis at the residue-level reveals potentially key interacting residues. Mutants with 3–5 residues changed to alanine have no measurable differences from wild-type IL-23 except for binding of and signaling blockade by the 7B7 anti-IL-23 antibody. The M5 IL-23 mutant differs from wild-type by five alanine substitutions and represents the dominant energetic epitope of 7B7. M5 shows a dramatic decrease in binding to BMS-986010 (which contains the 7B7 Fab), yet maintains functional activity, binding to p40 and p19 specific reagents, and maintains biophysical properties similar to wild-type IL-23 (monomeric state, thermal stability, and secondary structural features).
The role of information and communication technologies in using projective techniques as survey tools to meet the challenges of bounded rationalityDerek Bond Elaine Ramsey Article information:To cite this document:Derek Bond Elaine Ramsey, (2010),"The role of information and communication technologies in using projective techniques as survey tools to meet the challenges of bounded rationality"If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -Normal "mixed method" approaches to research -using standard quantitative surveys supported by qualitative methods such as semi-structured interviews, often fail to measure issues "outside of the fence". The purpose of this paper is to consider whether the challenges of bounded rationality can, in part, be addressed by including projective techniques within the "mixed methods" approach. In particular, it discusses the role of information and communication technologies (ICT) in such an approach. Design/methodology/approach -The results of an international pilot study into the use of projective techniques in assisting the evaluation of policies is outlined. The study is concerned with the response of small businesses to governments' policies aimed at encouraging the adoption of ICT. This is used as the basis of a discussion of the appropriateness of using ICT in such an approach. Findings -ICT could play an important role in the use of projective techniques -including design; improving reliability and validity; distribution; analysis and interpretation. Research limitations/implications -Much more research is needed before the appropriateness of (ICT based) projective techniques can be assessed fully. Practical implications -The lessons learnt from this pilot study about the use of projective techniques as part of a "mixed methods" survey methodology was explored. In particular, the paper provides some practical suggestions as to how ICT might be used to reduce the overheads involved in implementing projective techniques. Originality/value -For many people involved in traditional quantitative and qualitative research the usefulness and appropriateness of projective techniques have yet to be proven. This paper contributes some new thinking about how ICT might address some of the conc...
This paper considers recent developments in econometrics that have helped to resolve the apparent dichotomy between time‐series analysis and dynamic econometrics. In particular, the paper shows how the concepts of cointegration and error‐correction models can be used in the estimation of dynamic regional multipliers. Using the results of a pilot study for Northern Ireland it is shown how the techniques provide a new method for estimating the economic base, and an encompassing approach to early conflicting results.
This is a revised and extended version of the authors' 2003 Trinity Economic Paper. It describes Hamilton's (2001) approach to nonlinear econometric modelling and some of the methods of nonlinear optimization, as before, but adds significantly to the investigation of Hamilton's Gauss program for the implementation of his methodology. Specifically, it reports on the performance of this program using data relating to Hamilton's US Phillips curve example, the use of two versions of the Gauss software and a range of numerical optimization options. It also examines the impact of changes in initial parameter estimates, the use of algorithm switching strategies, and the effects of changes in the sample data on the results produced by Hamilton's procedure. The new results presented suggest some further clear conclusions that will be of value to those using Hamilton's method.J.E.L. Classification: C13, C51, C61
Summary Geographic information systems (GIS) have received considerable academic and practitioner attention in the last ten years. It is our view that these tools have been considerably oversold to public sector organisations‐particularly local government‐many of whom have failed to achieve the benefits they expected. In our paper, we attempt to develop a broad definition of GIS and discuss the relationship between GIS and policy analysis, spatial decision support systems, spatial analysis and spatial modelling. We also seek to explore how GIS fits into the management information systems and information architectures of public sector organisations and examine some of the human and organisational tensions which GIS adoption and use have brought about. Where possible, we have used examples of how GIS has been used to inform public development in several areas though these have generally been in academic settings and not in public sector organisations.
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