Modeling the peptide-T cell receptor interaction by the comparative molecular similarity indices analysis-soft independent modeling of class analogy technique

A set of 38 epitopes and 183 non-epitopes, which bind to alleles of the HLA-A3 supertype, was subjected to a combination of comparative molecular similarity indices analysis (CoMSIA) and soft independent modeling of class analogy (SIMCA). During the process of T cell recognition, T cell receptors (TCR) interact with the central section of the bound nonamer peptide; thus only positions 4−8 were considered in the study. The derived model distinguished 82% of the epitopes and 73% of the non-epitopes after cross-validation in five groups. The overall preference from the model is for polar amino acids with high electron density and the ability to form hydrogen bonds. These so-called “aggressive” amino acids are flanked by small-sized residues, which enable such residues to protrude from the binding cleft and take an active role in TCR-mediated T cell recognition. Combinations of “aggressive” and “passive” amino acids in the middle part of epitopes constitute a putative TCR binding motif

A comparative and longitudinal analysis of the evolving relationship between the environment and the strategy, structure and performance of selected organisations in the British carpet industry 1959-1986:a firms in sector perspective of organisational adaptation

Orthodox contingency theory links effective organisational performance to compatible relationships between the environment and organisation strategy and structure and assumes that organisations have the capacity to adapt as the environment changes. Recent contributions to the literature on organisation theory claim that the key to effective performance is effective adaptation which in turn requires the simultaneous reconciliation of efficiency and innovation which is afforded by an unique environment-organisation configuration. The literature on organisation theory recognises the continuing confusion caused by the fragmented and often conflicting results from cross-sectional studies. Although the case is made for longitudinal studies which comprehensively describe the evolving relationship between the environment and the organisation there is little to suggest how such studies should be executed in practice. Typically the choice is between the approaches of the historicised case study and statistical analysis of large populations which examine the relationship between environment and organisation strategy and/or structure and ignore the product-process relationship. This study combines the historicised case study and the multi-variable and ordinal scale approach of statistical analysis to construct an analytical framework which tracks and exposes the environment-organisation-performance relationship over time. The framework examines changes in the environment, strategy and structure and uniquely includes an assessment of the organisation's product-process relationship and its contribution to organisational efficiency and innovation. The analytical framework is applied to examine the evolving environment-organisation relationship of two organisations in the same industry over the same twenty-five year period to provide a sector perspective of organisational adaptation. The findings demonstrate the significance of the environment-organisation configuration to the scope and frequency of adaptation and suggest that the level of sector homogeneity may be linked to the level of product-process standardisation.

Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

Comparative genomic hybridization analysis of craniopharyngiomas

Object. Craniopharyngioma is the most common childhood brain tumor and is thought to arise from embryonic remnants of the Rathke pouch. Some craniopharyngiomas are monoclonal in origin and hence presumably harbor somatic genetic alterations, although the precise molecular mechanisms involved in craniopharyngioma development are unknown. The goal of this study was to identify genetic alterations in craniopharyngiomas. Methods. To gain insight into the molecular mechanisms involved in development of these tumors, the authors analyzed nine adamantinomatous craniopharyngiomas by using comparative genomic hybridization. Six tumors (67%) displayed at least one genomic alteration, and three had six or more alterations. Only two tumors displayed a decrease in DNA copy number, and in all others an increase in DNA copy number was noted. Conclusions. The authors conclude that a subset of craniopharyngiomas consists of monoclonal tumors arising from activation of oncogenes located at specific chromosomal loci.

A comparative molecular similarity indices (CoMSIA) study of peptide binding to the HLA-A3 superfamily

Epitope identification is the basis of modern vaccine design. The present paper studied the supermotif of the HLA-A3 superfamily, using comparative molecular similarity indices analysis (CoMSIA). Four alleles with high phenotype frequencies were used: A*1101, A*0301, A*3101 and A*6801. Five physicochemical properties—steric bulk, electrostatic potential, local hydro-phobicity, hydrogen-bond donor and acceptor abilities—were considered and ‘all fields’ models were produced for each of the alleles. The models have a moderate level of predictivity and there is a good correlation between the data. A revised HLA-A3 supermotif was defined based on the comparison of favoured and disfavoured properties for each position of the MHC bound peptide. The present study demonstrated that CoMSIA is an effective tool for studying peptide–MHC interactions.

Quantitative structure-activity relationships and the prediction of MHC supermotifs

The underlying assumption in quantitative structure–activity relationship (QSAR) methodology is that related chemical structures exhibit related biological activities. We review here two QSAR methods in terms of their applicability for human MHC supermotif definition. Supermotifs are motifs that characterise binding to more than one allele. Supermotif definition is the initial in silico step of epitope-based vaccine design. The first QSAR method we review here—the additive method—is based on the assumption that the binding affinity of a peptide depends on contributions from both amino acids and the interactions between them. The second method is a 3D-QSAR method: comparative molecular similarity indices analysis (CoMSIA). Both methods were applied to 771 peptides binding to 9 HLA alleles. Five of the alleles (A*0201, A* 0202, A*0203, A*0206 and A*6802) belong to the HLA-A2 superfamily and the other four (A*0301, A*1101, A*3101 and A*6801) to the HLA-A3 superfamily. For each superfamily, supermotifs defined by the two QSAR methods agree closely and are supported by many experimental data.

Differences between younger and older adults in the structure of suicidal intent and its correlates

OBJECTIVE: To analyze differences in the variables associated with severity of suicidal intent and in the main factors associated with intent when comparing younger and older adults. DESIGN: Observational, descriptive cross-sectional study. SETTING: Four general hospitals in Madrid, Spain. PARTICIPANTS: Eight hundred seventy suicide attempts by 793 subjects split into two groups: 18-54 year olds and subjects older than 55 years. MEASUREMENTS: The authors tested the factorial latent structure of suicidal intent through multigroup confirmatory factor analysis for categorical outcomes and performed statistical tests of invariance across age groups using the DIFFTEST procedure. Then, they tested a multiple indicators-multiple causes (MIMIC) model including different covariates regressed on the latent factor "intent" and performed two separate MIMIC models for younger and older adults to test for differential patterns. RESULTS: Older adults had higher suicidal intent than younger adults (z = 2.63, p = 0.009). The final model for the whole sample showed a relationship of intent with previous attempts, support, mood disorder, personality disorder, substance-related disorder, and schizophrenia and other psychotic disorders. The model showed an adequate fit (chi²[12] = 22.23, p = 0.035; comparative fit index = 0.986; Tucker-Lewis index = 0.980; root mean square error of approximation = 0.031; weighted root mean square residual = 0.727). All covariates had significant weights in the younger group, but in the older group, only previous attempts and mood disorders were significantly related to intent severity. CONCLUSIONS: The pattern of variables associated with suicidal intent varies with age. Recognition, and treatment of geriatric depression may be the most effective measure to prevent suicidal behavior in older adults.

The future of manufacturing

Anyone who looks at the title of this special issue will agree that the intent behind the preparation of this volume was ambitious: to predict and discuss “The Future of Manufacturing”. Will manufacturing be important in the future? Even though some sceptics might say not, and put on the table some old familiar arguments, we would strongly disagree. To bring subsidies for the argument we issued the call-for-papers for this special issue of Journal of Manufacturing Technology Management, fully aware of the size of the challenge in our hands. But we strongly believed that the enterprise would be worthwhile. The point of departure is the ongoing debate concerning the meaning and content of manufacturing. The easily visualised internal activity of using tangible resources to make physical products in factories is no longer a viable way to characterise manufacturing. It is now a more loosely defined concept concerning the organisation and management of open, interdependent, systems for delivering goods and services, tangible and intangible, to diverse types of markets. Interestingly, Wickham Skinner is the most cited author in this special issue of JMTM. He provides the departure point of several articles because his vision and insights have guided and inspired researchers in production and operations management from the late 1960s until today. However, the picture that we draw after looking at the contributions in this special issue is intrinsically distinct, much more dynamic, and complex. Seven articles address the following research themes: 1.new patterns of organisation, where the boundaries of firms become blurred and the role of the firm in the production system as well as that of manufacturing within the firm become contingent; 2.new approaches to strategic decision-making in markets characterised by turbulence and weak signals at the customer interface; 3.new challenges in strategic and operational decisions due to changes in the profile of the workforce; 4.new global players, especially China, modifying the manufacturing landscape; and 5.new techniques, methods and tools that are being made feasible through progress in new technological domains. Of course, many other important dimensions could be studied, but these themes are representative of current changes and future challenges. Three articles look at the first theme: organisational evolution of production and operations in firms and networks. Karlsson's and Skold's article represent one further step in their efforts to characterise “the extraprise”. In the article, they advance the construction of a new framework, based on “the network perspective” by defining the formal elements which compose it and exploring the meaning of different types of relationships. The way in which “actors, resources and activities” are conceptualised extends the existing boundaries of analytical thinking in operations management and open new avenues for research, teaching and practice. The higher level of abstraction, an intrinsic feature of the framework, is associated to the increasing degree of complexity that characterises decisions related to strategy and implementation in the manufacturing and operations area, a feature that is expected to become more and more pervasive as time proceeds. Riis, Johansen, Englyst and Sorensen have also based their article on their previous work, which in this case is on “the interactive firm”. They advance new propositions on strategic roles of manufacturing and discuss why the configuration of strategic manufacturing roles, at the level of the network, will become a key issue and how the indirect strategic roles of manufacturing will become increasingly important. Additionally, by considering that value chains will become value webs, they predict that shifts in strategic manufacturing roles will look like a sequence of moves similar to a game of chess. Then, lastly under the first theme, Fleury and Fleury develop a conceptual framework for the study of production systems in general derived from field research in the telecommunications industry, here considered a prototype of the coming information society and knowledge economy. They propose a new typology of firms which, on certain dimensions, complements the propositions found in the other two articles. Their telecoms-based framework (TbF) comprises six types of companies characterised by distinct profiles of organisational competences, which interact according to specific patterns of relationships, thus creating distinct configurations of production networks. The second theme is addressed by Kyläheiko and SandstroÍm in their article “Strategic options based framework for management of dynamic capabilities in manufacturing firms”. They propose a new approach to strategic decision-making in markets characterised by turbulence and weak signals at the customer interface. Their framework for a manufacturing firm in the digital age leads to active asset selection (strategic investments in both tangible and intangible assets) and efficient orchestrating of the global value net in “thin” intangible asset markets. The framework consists of five steps based on Porter's five-forces model, the resources-based view, complemented by means of the concepts of strategic options and related flexibility issues. Thun, GroÍssler and Miczka's contribution to the third theme brings the human dimension to the debate regarding the future of manufacturing. Their article focuses on the challenges brought to management by the ageing of workers in Germany but, in the arguments that are raised, the future challenges associated to workers and work organisation in every production system become visible and relevant. An interesting point in the approach adopted by the authors is that not only the factual problems and solutions are taken into account but the perception of the managers is brought into the picture. China cannot be absent in the discussion of the future of manufacturing. Therefore, within the fourth theme, Vaidya, Bennett and Liu provide the evidence of the gradual improvement of Chinese companies in the medium and high-tech sectors, by using the revealed comparative advantage (RCA) analysis. The Chinese evolution is shown to be based on capabilities developed through combining international technology transfer and indigenous learning. The main implication for the Western companies is the need to take account of the accelerated rhythm of capability development in China. For other developing countries China's case provides lessons of great importance. Finally, under the fifth theme, Kuehnle's article: “Post mass production paradigm (PMPP) trajectories” provides a futuristic scenario of what is already around us and might become prevalent in the future. It takes a very intensive look at a whole set of dimensions that are affecting manufacturing now, and will influence manufacturing in the future, ranging from the application of ICT to the need for social transparency. In summary, this special issue of JMTM presents a brief, but undisputable, demonstration of the possible richness of manufacturing in the future. Indeed, we could even say that manufacturing has no future if we only stick to the past perspectives. Embracing the new is not easy. The new configurations of production systems, the distributed and complementary roles to be performed by distinct types of companies in diversified networked structures, leveraged by the new emergent technologies and associated the new challenges for managing people, are all themes that are carriers of the future. The Guest Editors of this special issue on the future of manufacturing are strongly convinced that their undertaking has been worthwhile.

Environmental and nature conservation : a facet study of concern for the quality of the natural environment

A multi-variate descriptive model of environmental and nature conservation attitudes and values is proposed and empirically supported. A mapping sentence is developed out of analysis of data from a series of Repertory Grid interviews addressing conservation employees' attitudes towards their profession's activities. The research is carried out within the meta-theoretical framework of Facet Theory. A mapping sentence is developed consisting of 9 facets. From the mapping sentence 3 questionnaires were constructed viewing the selective orientations towards environmental concern. A mapping sentence and facet model is developed for each study. Once the internal structure of this model had been established using Similarity Structure Analysis, the elements of the facets are subjected to Partial Order Scalogram Analysis with base coordinates. A questionnaire was statistically analysed to assess the relationship between facet elements and 4 measures of attitudes towards, and involvement with, conservation. This enabled the comparison of the relative strengths of attitudes associated with each facet element and each measure of conservation attitude. In general, the relationship between the social value of conservation and involvement pledges to conservation were monotonic; perceived importance of a conservation issue appearing predictive of personal involvement. Furthermore, the elements of the life area and scale facets were differentially related to attitude measures. The multi-variate descriptive model of environmental conservation values and attitudes is discussed in relation to its implications for psychological research into environmental concern and for environmental and nature conservation.

Syndromes of collateral-reported psychopathology for ages 18-59 in 18 societies

The purpose was to advance research and clinical methodology for assessing psychopathology by testing the international generalizability of an 8-syndrome model derived from collateral ratings of adult behavioral, emotional, social, and thought problems. Collateral informants rated 8,582 18-59-year-old residents of 18 societies on the Adult Behavior Checklist (ABCL). Confirmatory factor analyses tested the fit of the 8-syndrome model to ratings from each society. The primary model fit index (Root Mean Square Error of Approximation) showed good model fit for all societies, while secondary indices (Tucker Lewis Index, Comparative Fit Index) showed acceptable to good fit for 17 societies. Factor loadings were robust across societies and items. Of the 5,007 estimated parameters, 4 (0.08%) were outside the admissible parameter space, but 95% confidence intervals included the admissible space, indicating that the 4 deviant parameters could be due to sampling fluctuations. The findings are consistent with previous evidence for the generalizability of the 8-syndrome model in self-ratings from 29 societies, and support the 8-syndrome model for operationalizing phenotypes of adult psychopathology from multi-informant ratings in diverse societies. © 2014 Asociación Española de Psicología Conductual.

A comparison of denoising methods for X-ray fluoroscopic images

Fluoroscopic images exhibit severe signal-dependent quantum noise, due to the reduced X-ray dose involved in image formation, that is generally modelled as Poisson-distributed. However, image gray-level transformations, commonly applied by fluoroscopic device to enhance contrast, modify the noise statistics and the relationship between image noise variance and expected pixel intensity. Image denoising is essential to improve quality of fluoroscopic images and their clinical information content. Simple average filters are commonly employed in real-time processing, but they tend to blur edges and details. An extensive comparison of advanced denoising algorithms specifically designed for both signal-dependent noise (AAS, BM3Dc, HHM, TLS) and independent additive noise (AV, BM3D, K-SVD) was presented. Simulated test images degraded by various levels of Poisson quantum noise and real clinical fluoroscopic images were considered. Typical gray-level transformations (e.g. white compression) were also applied in order to evaluate their effect on the denoising algorithms. Performances of the algorithms were evaluated in terms of peak-signal-to-noise ratio (PSNR), signal-to-noise ratio (SNR), mean square error (MSE), structural similarity index (SSIM) and computational time. On average, the filters designed for signal-dependent noise provided better image restorations than those assuming additive white Gaussian noise (AWGN). Collaborative denoising strategy was found to be the most effective in denoising of both simulated and real data, also in the presence of image gray-level transformations. White compression, by inherently reducing the greater noise variance of brighter pixels, appeared to support denoising algorithms in performing more effectively. © 2012 Elsevier Ltd. All rights reserved.

Increased risk of diabetes mellitus among persons with psychotic symptoms:results from the WHO World Health Survey

OBJECTIVE: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population. METHOD: Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004. RESULTS: An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999). CONCLUSIONS: Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.

From marine ecology to crime analysis: improving the detection of serial sexual offences using a taxonomic similarity measure

Jaccard has been the choice similarity metric in ecology and forensic psychology for comparison of sites or offences, by species or behaviour. This paper applies a more powerful hierarchical measure - taxonomic similarity (s), recently developed in marine ecology - to the task of behaviourally linking serial crime. Forensic case linkage attempts to identify behaviourally similar offences committed by the same unknown perpetrator (called linked offences). s considers progressively higher-level taxa, such that two sites show some similarity even without shared species. We apply this index by analysing 55 specific offence behaviours classified hierarchically. The behaviours are taken from 16 sexual offences by seven juveniles where each offender committed two or more offences. We demonstrate that both Jaccard and s show linked offences to be significantly more similar than unlinked offences. With up to 20% of the specific behaviours removed in simulations, s is equally or more effective at distinguishing linked offences than where Jaccard uses a full data set. Moreover, s retains significant difference between linked and unlinked pairs, with up to 50% of the specific behaviours removed. As police decision-making often depends upon incomplete data, s has clear advantages and its application may extend to other crime types. Copyright © 2007 John Wiley & Sons, Ltd.