Analysis of radicals and radical reaction products in cell signalling and biomolecular damage:the long hard road to gold-standard measures

The field of free radical biology and medicine continues to move at a tremendous pace, with a constant flow of ground-breaking discoveries. The following collection of papers in this issue of Biochemical Society Transactions highlights several key areas of topical interest, including the crucial role of validated measurements of radicals and reactive oxygen species in underpinning nearly all research in the field, the important advances being made as a result of the overlap of free radical research with the reinvigorated field of lipidomics (driven in part by innovations in MS-based analysis), the acceleration of new insights into the role of oxidative protein modifications (particularly to cysteine residues) in modulating cell signalling, and the effects of free radicals on the functions of mitochondria, extracellular matrix and the immune system. In the present article, we provide a brief overview of these research areas, but, throughout this discussion, it must be remembered that it is the availability of reliable analytical methodologies that will be a key factor in facilitating continuing developments in this exciting research area.

The emergence of knowledge exchange:an agent-based model of a software market

We investigate knowledge exchange among commercial organizations, the rationale behind it, and its effects on the market. Knowledge exchange is known to be beneficial for industry, but in order to explain it, authors have used high-level concepts like network effects, reputation, and trust. We attempt to formalize a plausible and elegant explanation of how and why companies adopt information exchange and why it benefits the market as a whole when this happens. This explanation is based on a multiagent model that simulates a market of software providers. Even though the model does not include any high-level concepts, information exchange naturally emerges during simulations as a successful profitable behavior. The conclusions reached by this agent-based analysis are twofold: 1) a straightforward set of assumptions is enough to give rise to exchange in a software market, and 2) knowledge exchange is shown to increase the efficiency of the market.

Multinationality-performance relationship:a meta-analysis

- We conduct a Meta-analysis of 54 papers that study the relationship between multinationality and firm performance. The aim is to understand if any systematic relationships exist between the characteristics of each study and the reported results of linear and curvilinear regressions to examine the multinationality-performance relationship. - Our main finding, robust to different specifications and to different weights for each observation, is that when analysis is based on non-US data, the reported return to multinationality is higher. However, this relationship for non-US firms is usually U-shaped rather than inverted U-shaped. This indicates that US firms face lower returns to internationalization than other firms but are less likely to incur losses in the early stages of internationalization. - The findings also highlight the differences that are reported when comparing regression and non-regression based techniques. Our results suggest that in this area regression based analysis is more reliable than say ANOVA or other related approaches. - Other characteristics that influence the estimated rate of return and its shape across different studies are: the measure of multinationality used; size distribution of the sample; and the use of market-based indicators to measure firm performance. Finally, we find no evidence of publication bias.

Statistical mechanics of low-density parity-check codes

We review recent theoretical progress on the statistical mechanics of error correcting codes, focusing on low-density parity-check (LDPC) codes in general, and on Gallager and MacKay-Neal codes in particular. By exploiting the relation between LDPC codes and Ising spin systems with multispin interactions, one can carry out a statistical mechanics based analysis that determines the practical and theoretical limitations of various code constructions, corresponding to dynamical and thermodynamical transitions, respectively, as well as the behaviour of error-exponents averaged over the corresponding code ensemble as a function of channel noise. We also contrast the results obtained using methods of statistical mechanics with those derived in the information theory literature, and show how these methods can be generalized to include other channel types and related communication problems.

Statistical mechanics of broadcast channels using low-density parity-check codes

We investigate the use of Gallager's low-density parity-check (LDPC) codes in a degraded broadcast channel, one of the fundamental models in network information theory. Combining linear codes is a standard technique in practical network communication schemes and is known to provide better performance than simple time sharing methods when algebraic codes are used. The statistical physics based analysis shows that the practical performance of the suggested method, achieved by employing the belief propagation algorithm, is superior to that of LDPC based time sharing codes while the best performance, when received transmissions are optimally decoded, is bounded by the time sharing limit.

Inventory parameter management and focused continuous improvement for repetitive batch manufacturers

What this thesis proposes is a methodology to assist repetitive batch manufacturers in the adoption of certain aspects of the Lean Production principles. The methodology concentrates on the reduction of inventory through the setting of appropriate batch sizes, taking account of the effect of sequence dependent set-ups and the identification and elimination of bottlenecks. It uses a simple Pareto and modified EBQ based analysis technique to allocate items to period order day classes based on a combination of each item's annual usage value and set-up cost. The period order day classes the items are allocated to are determined by the constraints limits in the three measured dimensions, capacity, administration and finance. The methodology overcomes the limitations associated with MRP in the area of sequence dependent set-ups, and provides a simple way of setting planning parameters taking this effect into account by concentrating on the reduction of inventory through the systematic identification and elimination of bottlenecks through set-up reduction processes, so allowing batch sizes to reduce. It aims to help traditional repetitive batch manufacturers in a route to continual improvement by: Highlighting those areas where change would bring the greatest benefits. Modelling the effect of proposed changes. Quantifying the benefits that could be gained through implementing the proposed changes. Simplifying the effort required to perform the modelling process. It concentrates on increasing flexibility through managed inventory reduction through rationally decreasing batch sizes, taking account of sequence dependent set-ups and the identification and elimination of bottlenecks. This was achieved through the development of a software modelling tool, and validated through a case study approach.

Three-factor models versus time series models:quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data

Signal integration determines cell fate on the cellular level, affects cognitive processes and affective responses on the behavioural level, and is likely to be involved in psychoneurobiological processes underlying mood disorders. Interactions between stimuli may subjected to time effects. Time-dependencies of interactions between stimuli typically lead to complex cell responses and complex responses on the behavioural level. We show that both three-factor models and time series models can be used to uncover such time-dependencies. However, we argue that for short longitudinal data the three factor modelling approach is more suitable. In order to illustrate both approaches, we re-analysed previously published short longitudinal data sets. We found that in human embryonic kidney 293 cells cells the interaction effect in the regulation of extracellular signal-regulated kinase (ERK) 1 signalling activation by insulin and epidermal growth factor is subjected to a time effect and dramatically decays at peak values of ERK activation. In contrast, we found that the interaction effect induced by hypoxia and tumour necrosis factor-alpha for the transcriptional activity of the human cyclo-oxygenase-2 promoter in HEK293 cells is time invariant at least in the first 12-h time window after stimulation. Furthermore, we applied the three-factor model to previously reported animal studies. In these studies, memory storage was found to be subjected to an interaction effect of the beta-adrenoceptor agonist clenbuterol and certain antagonists acting on the alpha-1-adrenoceptor / glucocorticoid-receptor system. Our model-based analysis suggests that only if the antagonist drug is administer in a critical time window, then the interaction effect is relevant.

Do many hands make light work? How to overcome social loafing and gain motivation in work teams

Purpose – The purpose of this paper is to challenge the assumption that process losses of individuals working in teams are unavoidable. The paper aims to challenge this assumption on the basis of social identity theory and recent research. Design/methodology/approach – The approach adopted in this paper is to review the mainstream literature providing strong evidence for motivation problems of individuals working in groups. Based on more recent literature, innovative ways to overcome these problems are discussed. Findings – A social identity-based analysis and recent findings summarized in this paper show that social loafing can be overcome and that even motivation gains in group work can be expected when groups are important for the individual group members' self-concepts. Practical implications – The paper provides human resource professionals and front-line managers with suggestions as to how individual motivation and performance might be increased when working in teams. Originality/value – The paper contributes to the literature by challenging the existing approach to reducing social loafing, i.e. individualizing workers as much as possible, and proposes a team-based approach instead to overcome motivation problems.

Selling, resistance and reconciliation:a critical discursive approach to subsidiary role evolution in MNEs

Studies of political dynamics between multinational enterprise (MNE) parents and subsidiaries during subsidiary role evolution have focused largely on control and resistance. This paper adopts a critical discursive approach to enable an exploration of subtle dynamics in the way that both headquarters and subsidiaries subjectively reconstruct their independent-interdependent relationships with each other during change. We draw from a real-time qualitative study of a revealing case of charter change in an important European subsidiary of an MNE attempting to build closer integration across European country operations. Our results illustrate the role of three discourses – selling, resistance and reconciliation – in the reconstruction of the subsidiary–parent relationship. From this analysis we develop a process framework that elucidates the important role of these three discourses in the reconstruction of subsidiary roles, showing how resistance is not simply subversive but an important part of integration. Our findings contribute to a better understanding of the micro-level political dynamics in subsidiary role evolution, and of how voice is exercised in MNEs. This study also provides a rare example of discourse-based analysis in an MNE context, advancing our knowledge of how discursive methods can help to advance international business research more generally.

Global optimisation of cold-formed steel sections

In this thesis, standard algorithms are used to carry out the optimisation of cold-formed steel purlins such as zed, channel and sigma sections, which are assumed to be simply supported and subjected to a gravity load. For zed, channel and sigma section, the local buckling, distortional buckling and lateral-torsional buckling are considered respectively herein. Currently, the local buckling is based on the BS 5950-5:1998 and EN 1993-1-3:2006. The distortional buckling is calculated by the direct strength method employing the elastic distortional buckling which is calculated by three available approaches such as Hancock (1995), Schafer and Pekoz (1998), Yu (2005). In the optimisation program, the lateral-torsional buckling based on BS 5950-5:1998, AISI and analytical model of Li (2004) are investigated. For the optimisation program, the programming codes are written for optimisation of channel, zed and sigma beam. The full study has been coded into a computer-based analysis program (MATLAB).

Translation practices at the European Central Bank with reference to metaphors

The European Union institutions represent a complex setting and a specific case of institutional translation. The European Central Bank (ECB) is a particular context as the documents translated belong to the field of economics and, thus, contain many specialised terms and neologisms that pose challenges to translators. This study aims to investigate the translation practices at the ECB, and to analyse their effects on the translated texts. In order to illustrate the way texts are translated at the ECB, the thesis will focus on metaphorical expressions and the conceptual metaphors by which they are sanctioned. Metaphor is often associated with literature and less with specialised texts. However, according to Lakoff and Johnson’s (1980) conceptual metaphor theory, our conceptual system is fundamentally metaphorical in nature and metaphors are pervasive elements of thought and speech. The corpus compiled comprises economic documents translated at the ECB, mainly from English into Romanian. Using corpus analysis, the most salient metaphorical expressions were identified in the source and target texts and explained with reference to the main conceptual metaphors. Translation strategies are discussed on the basis of a comparison of the source and target texts. The text-based analysis is complemented by questionnaires distributed to translators, which give insights into the institution’s translation practices. As translation is an institutional process, translators have to follow certain guidelines and practices; these are discussed with reference to translators’ agency. A gap was identified in the field of institutional translation. The translation process in the EU institutions has been insufficiently explored, especially regarding the new languages of the European Union. By combining the analysis of the institutional practices, the texts produced in the institution and the translators’ work (by the questionnaires distributed to translators), this thesis intends to bring a contribution to institutional translation and metaphor translation, particularly regarding a new EU language, Romanian.

Dissociable brain structural changes associated with predisposition, resilience, and disease expression in bipolar disorder

Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states. Copyright © 2009 Society for Neuroscience.

Gene network and proteomic analyses of cardiac responses to pathological and physiological stress

Background—The molecular mechanisms underlying similarities and differences between physiological and pathological left ventricular hypertrophy (LVH) are of intense interest. Most previous work involved targeted analysis of individual signaling pathways or screening of transcriptomic profiles. We developed a network biology approach using genomic and proteomic data to study the molecular patterns that distinguish pathological and physiological LVH. Methods and Results—A network-based analysis using graph theory methods was undertaken on 127 genome-wide expression arrays of in vivo murine LVH. This revealed phenotype-specific pathological and physiological gene coexpression networks. Despite >1650 common genes in the 2 networks, network structure is significantly different. This is largely because of rewiring of genes that are differentially coexpressed in the 2 networks; this novel concept of differential wiring was further validated experimentally. Functional analysis of the rewired network revealed several distinct cellular pathways and gene sets. Deeper exploration was undertaken by targeted proteomic analysis of mitochondrial, myofilament, and extracellular subproteomes in pathological LVH. A notable finding was that mRNA–protein correlation was greater at the cellular pathway level than for individual loci. Conclusions—This first combined gene network and proteomic analysis of LVH reveals novel insights into the integrated pathomechanisms that distinguish pathological versus physiological phenotypes. In particular, we identify differential gene wiring as a major distinguishing feature of these phenotypes. This approach provides a platform for the investigation of potentially novel pathways in LVH and offers a freely accessible protocol (http://sites.google.com/site/cardionetworks) for similar analyses in other cardiovascular diseases.

A template for externalisation-internalisation decisions in virtual enterprises

Recognising the importance of alliance decision making in a virtual enterprise (VE), this paper proposes an analysis template to facilitate this process. The existing transaction-cost and resource-based theories in the literature are first reviewed, showing some deficiencies in both type of theories, and the potential of the resource based explanations. The paper then goes on to propose a resource-based analysis template, integrating both the motives of using certain business forms and the factors why different forms help achieve different objectives, Resource-combination effectiveness, management complexity and flexibility are identified as the three factors providing fundamental explanations of an organization's alliance making decision process. The template provides a comprehensive and generic approach for analysing alliance decisions.