Innate recognition of apoptotic cells:novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells-apoptotic cell-associated molecular patterns (ACAMPs)-that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V-and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs. © 2013 Macmillan Publishers Limited All rights reserved.

Examination of the predictive value of structural magnetic resonance scans in bipolar disorder:a pattern classification approach

Background - Bipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD. Method - GPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls. Results - The diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD. Conclusions - Our results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.

Design and designing:a critical introduction

Design and Designing provides a broad and critical understanding of what is essentially a practical subject. Designing today is less a craft and more a part of the knowledge economy. It's all about knowing how to acquire knowledge and how to apply it creatively. Design and Designing covers the design process, modelling and drawing, working with clients, production and consumption, sustainability, professional practice and design futures. Chapters are written by expert teachers and practitioners from around the globe, each presenting an accessible and engaging overview of their field of design. Every chapter is highly illustrated with a combination of images and information boxes, which extend or highlight key material. Each section concludes with a design project, a hands-on activity for the reader. Design and Designing covers the full spectrum of design types, from graphic communication to product design, from fashion to games design, setting every type in its aesthetic, ethical and social contexts. With this essential book, readers will learn from today's best practice and best thinking in design, they will develop a critical sense, and become the designers of tomorrow.

The impact of context on pattern category learning and representation

Context traditionally has been regarded in vision research as a determinant for the interpretation of sensory information on the basis of previously acquired knowledge. Here we propose a novel, complementary perspective by showing that context also specifically affects visual category learning. In two experiments involving sets of Compound Gabor patterns we explored how context, as given by the stimulus set to be learned, affects the internal representation of pattern categories. In Experiment 1, we changed the (local) context of the individual signal classes by changing the configuration of the learning set. In Experiment 2, we varied the (global) context of a fixed class configuration by changing the degree of signal accentuation. Generalization performance was assessed in terms of the ability to recognize contrast-inverted versions of the learning patterns. Both contextual variations yielded distinct effects on learning and generalization thus indicating a change in internal category representation. Computer simulations suggest that the latter is related to changes in the set of attributes underlying the production rules of the categories. The implications of these findings for phenomena of contrast (in)variance in visual perception are discussed.

Hierarchical Logical Description and Neural Recognition of Complex Patterns

Authors suggested earlier hierarchical method for definition of class description at pattern recognition problems solution. In this paper development and use of such hierarchical descriptions for parallel representation of complex patterns on the base of multi-core computers or neural networks is proposed.

A Statistical Convergence Aplication for the Hopfield Networks

When Recurrent Neural Networks (RNN) are going to be used as Pattern Recognition systems, the problem to be considered is how to impose prescribed prototype vectors ξ^1,ξ^2,...,ξ^p as fixed points. The synaptic matrix W should be interpreted as a sort of sign correlation matrix of the prototypes, In the classical approach. The weak point in this approach, comes from the fact that it does not have the appropriate tools to deal efficiently with the correlation between the state vectors and the prototype vectors The capacity of the net is very poor because one can only know if one given vector is adequately correlated with the prototypes or not and we are not able to know what its exact correlation degree. The interest of our approach lies precisely in the fact that it provides these tools. In this paper, a geometrical vision of the dynamic of states is explained. A fixed point is viewed as a point in the Euclidean plane R2. The retrieving procedure is analyzed trough statistical frequency distribution of the prototypes. The capacity of the net is improved and the spurious states are reduced. In order to clarify and corroborate the theoretical results, together with the formal theory, an application is presented

Projective Methods of Image Recognition

We propose a method for image recognition on the base of projections. Radon transform gives an opportunity to map image into space of its projections. Projection properties allow constructing informative features on the base of moments that can be successfully used for invariant recognition. Offered approach gives about 91-97% of correct recognition.

Improved Hybrid Model of HMM/GMM for Speech Recognition

In this paper, we propose a speech recognition engine using hybrid model of Hidden Markov Model (HMM) and Gaussian Mixture Model (GMM). Both the models have been trained independently and the respective likelihood values have been considered jointly and input to a decision logic which provides net likelihood as the output. This hybrid model has been compared with the HMM model. Training and testing has been done by using a database of 20 Hindi words spoken by 80 different speakers. Recognition rates achieved by normal HMM are 83.5% and it gets increased to 85% by using the hybrid approach of HMM and GMM.

How trust affects the use of information obtained through intra- and extraorganizational relationships?

We have limited knowledge on the potential pattern similarities/differences of trust’s role that may exist in information use obtained through intra- and extra-organizational relationships. This study addresses this question by investigating how trust leads to information use. Data from 338 intra-organizational and a sub-ample of 158 interorganizational dyadic information exchange-relationships showed that trust is an important driver of the utilization of market information in both cases. Trust has no direct relationship to information use, instead has a strong indirect effect through a mediator, perceived quality of information. The effects of trust on the use of information obtained through inter- and extra-organizational dyadic relationships proved to be similar.

Pattern of nutrient availability and plant community assemblage in Everglades Tree Islands, Florida, USA

We address the relative importance of nutrient availability in relation to other physical and biological factors in determining plant community assemblages around Everglades Tree Islands (Everglades National Park, Florida, USA). We carried out a one-time survey of elevation, soil, water level and vegetation structure and composition at 138 plots located along transects in three tree islands in the Park’s major drainage basin. We used an RDA variance partitioning technique to assess the relative importance of nutrient availability (soil N and P) and other factors in explaining herb and tree assemblages of tree island tail and surrounded marshes. The upland areas of the tree islands accumulate P and show low N concentration, producing a strong island-wide gradient in soil N:P ratio. While soil N:P ratio plays a significant role in determining herb layer and tree layer community assemblage in tree island tails, nevertheless part of its variance is shared with hydrology. The total species variance explained by the predictors is very low. We define a strong gradient in nutrient availability (soil N:P ratio) closely related to hydrology. Hydrology and nutrient availability are both factors influencing community assemblages around tree islands, nevertheless both seem to be acting together and in a complex mechanism. Future research should be focused on segregating these two factors in order to determine whether nutrient leaching from tree islands is a factor determining community assemblages and local landscape pattern in the Everglades, and how this process might be affected by water management.

Essays of strategic alliance portfolio configuration—Its performance properties, strategic antecedents and consequential effects on multinational firms' continuing foreign expansion

This dissertation focused on an increasingly prevalent phenomenon in today's global business environment—strategic alliance portfolio. Building on resource-based view, resource dependency theory and real options theory, this dissertation adopted a multi-dimensional perspective to examine the performance implications, strategic antecedents of alliance portfolio configuration, and its strategic effects on firms' decision-making on their continuing foreign expansion. The dissertation consisted of three interrelated essays, each of which dealt with a specific research question. In the first essay I applied a two-dimensional construct that embraces both alliance relations' and alliance partners' attributes to illustrate alliance portfolio configuration. Based on this framework, a longitudinal study was conducted attempting to explore the performance properties of alliance portfolio configuration. The results revealed that alliance diversity and partner diversity have different relative contributions to firms' economic performance. The relationship between alliance portfolio configuration and firm performance was shaped by degree of multinationality in a curvilinear pattern. The second essay attempted to identify the firm level driving forces of alliance portfolio configuration and how these forces interacting with firms' internationalization influence firms' strategic choices on alliance portfolio configuration. The empirical results indicated that past alliance experience, slack resource and firms' brand images are three critical determinants shaping alliance portfolios, but those shaping relationships are conditioned by firms' multinationality. The third essay primarily employed real options theory to build a conceptual framework, revealing how country-, alliance portfolio-, firm-, and industry level factors and their interactions influence firms' strategic decision-making on post-entry continuing expansion in foreign markets. The two empirical studies were resided in global hospitality and travel industries and use panel data to test the relevant theoretical models. Overall, the dissertation advanced and enriched the theoretical domain of alliance portfolio. It particularly shed valuable insights on three fundamental questions in the domain of alliance portfolio research, namely "if and how alliance portfolios contribute to firms' economic performance"; "what determines the appearance of alliance portfolios”; and "how alliance portfolios affect firms' strategic decision-making". This dissertation also extended the international business and strategic management research on service multinationals' foreign expansion and performance.

A Longitudinal Study of Consumer Perceptions of Travel Websites: The Case of Hong Kong

Knowing how consumers perceive travel websites can help practitioners better understand consumers’ online requirements. This paper reports the findings of a longitudinal study that investigated the changes and trends in the profile and behavior of online travel-website users in Hong Kong. The profiles of e-buyers and e-browsers in 2009, when compared with those established by prior studies conducted in 2000 and 2007, point in a new direction for practitioners and researchers investigating online travelwebsite user behavior. The results indicated that more middle-aged consumers have become online travel-website users, and that website security and price are perceived to be the most important factors for travel-website use by both e-browsers and e-buyers.

Establishing a baseline of psychometric estimates of measurement of intercultural competence of Ukrainian faculty: Setting the stage for domestic and global intercultural understanding

Post-Soviet Ukraine is in a time of upheaval and transition. Internal relations between pro-Western and pro-Russian supporters have deteriorated in the light of recent political events of Euro Revolution, Russia's occupation of the Crimean peninsula, and the militant confrontations in the southeastern regions of the country. In the light of these developments, intercultural competence is greatly needed to alleviate domestic tensions and enable effective intercultural communication with the representatives of different cultures within the country and beyond its borders.^ This study established a baseline of psychometric estimates of intercultural competence of Ukrainian higher education faculty. A sample of 276 professors of different academic majors from one university in Western Ukraine participated in the research. The Global Perspective Inventory (GPI; Merrill, Braskamp, & Braskamp, 2012) was chosen as a research instrument to measure intercultural competence of the faculty members. The GPI takes into account cognitive, intrapersonal, and interpersonal domains, each of which contains two scales reflective of theories of cultural development and intercultural communication – Cognitive-Knowing, Cognitive-Knowledge, Intrapersonal-Identity, Intrapersonal-Affect, Interpersonal-Social Responsibility, and Interpersonal-Social Interaction. Because the research instrument has neither been previously used as a measure of intercultural competence, nor administered in Ukraine, it was cross-validated using a Table of Specification (Newman, Lim, & Pineda, 2013) and two sets of factor analyses. As a result, a modified version of the GPI was created for use in Ukraine.^ Multiple linear regression analyses were used to test relationships between the participants' GPI scores on intercultural competence, and several independent variables that consisted of academic discipline, intercultural experience, and how long the participants taught at the university. The analyses determined a positive relationship between the scores on three out of six scales of the original version and two out of five scales of the modified version of the GPI and all the independent variables simultaneously. The relationship between the faculty responses on the six scales of both GPI versions and the independent variables controlling for each other produced mixed results. A unique role of intercultural professional development in predicting intercultural competence was discussed.^

A objetivação da linguagem no (con)texto do vestibular : mo(vi)mentos na história e no político

In this study, we join up in the theoretical assumptions of the French Discourse Analysis in order to analyze effects of the demand of objectification of language in the context of vestibular essays. More specifically, we analyze the operation of said objectification via discourses constructed by the traditional vestibular exam due to the requirement to have, in the students’ essays, paraphrases of statements from the motivating texts (TM) of the test in question. From our perspective, the objectification mechanism of language, the paraphrase, in the vestibular, its logic of clarity and non-contradiction of ideas, is made by (in)determination of senses in the order of its speech and, also, in its practice: the correction of the vestibular essay. Therefore, in spite of what is assumed as guarantee to language in the moment of the vestibular essay, we suggest there are regularization-recognition conflicts of same senses— the constitutive senses of TM — in the evaluative speech of two vestibular-essay correctors(CA and CB). These correctors, with their history of reading (grammar and Linguistic Textual), stress the concept of paraphrase taken by the vestibular instance for the correction of students’ essays. Such stress creates a dispute of speeches: the speech of knowledge (university policy) versus the speech of produce (neoliberal policy); the latter as reading policy that favors literal meanings, consensus. Because of all this, we question: what are the effects of senses produced in (and about) vestibular essays by the demand of determining of the saying there instituted? To answer this question, we build analysis from clippings of documents that regulate the vestibular exam (institutional texts) in our country and, also, analysis of two vestibular essays in which at times appear, at times not, according to the judgment of CA and CB of essays, paraphrases of TM statements of the essay. The analysis, in theory, punctuates effects of sense of the objectification process of the saying in vestibular, and primarily the rarefaction of legal-position subject-of-knowing by the current institution of the subject-of-making. Moreover, our work comprises affiliations of sense that relates to the subject-speech relationship in evaluative exercise of vestibular essays, on the question of authorship.

Structural Basis of RNA Recognition by Mycobacterium tuberculosis MazF Homologues

The MazEF toxin-antitoxin (TA) system consists of the antitoxin MazE and the toxin MazF. MazF is a sequence-specific endoribonuclease that upon activation causes cellular growth arrest and increass the level of persisters. Moreover, MazF-induced cells are in a quasi-dormant state that cells remain metabolically active while stop dividing. The quasi-dormancy is similar to the nonreplicating state of M. tuberculosis during latent tuberculosis, thus suggesting the role of mazEF in M. tuberculosis dormancy and persistence. M. tuberculosis has nine mazEF TA modules, each with different RNA cleavage specificities and implicated in selective gene expression during stress conditions. To date only the Bacillus subtilis MazF-RNA complex structure has been determined. As M. tuberculosis MazF homologues recognize distinct RNA sequences, their molecular mechanisms of substrate specificity remain unclear. By taking advantage of X-ray crystallography, we have determined structures of two M. tuberculosis MazF-RNA complexes, MazF-mt1 (Rv2801c) and MazF-mt3 (Rv1991c) in complex with an uncleavable RNA substrate. These structures have provided the molecular basis of sequence-specific RNA recognition and cleavage by MazF toxins.

Both MazF-mt1-RNA and MazF-mt3-RNA complexes showed similar structural organization with one molecule of RNA bound to a MazF-mt1 or MazF-mt3 dimer and occupying the same pocket within the MazF dimer interface. Similar to B. subtilis MazF-RNA complex, MazF-mt1 and MazF-mt3 displayed a conserved active site architecture, where two highly conserved residues, Arg and Thr, form hydrogen bonds with the scissile phosphate group in the cleavage site of the bound RNA. The MazF-mt1-RNA complex also showed specific interactions with its three-base RNA recognition element. Compared with the B. subtilis MazF-RNA complex, our structures showed that residues involved in sequence-specific recognition of target RNA vary between the MazF homologues, therefore explaining the molecular basis for their different RNA recognition sequences. In addition, local conformational changes of the loops in the RNA binding site of MazF-mt1 appear to play a role in MazF targeting different RNA lengths and sequences. In contrast, the MazF-mt3-RNA complex is in a non-optimal RNA binding state with a symmetry-related MazF-mt3 molecule found to make interactions with the bound RNA in the crystal. The crystal-packing interactions were further examined by isothermal titration calorimetry (ITC) studies on selected MazF-mt3 mutants. Our attempts to utilize a MazF-mt3 mutant bearing mutations involved in crystal contacts all crystallized with few nucleotides, which are still found to interact with a symmetry mate. However, these different crystal forms revealed the conformational flexibility of loops in the RNA binding interface of MazF-mt3, suggesting their role in RNA binding and recognition, which will require further studies on additional MazF-mt3-RNA complex interactions.

In conclusion, the structures of the MazF-mt1-RNA and MazF-mt3-RNA complexes provide the first structural information on any M. tuberculosis MazF homologues. Supplemented with structure-guided mutational studies on MazF toxicity in vivo, this study has addressed the structural basis of different RNA cleavage specificities among MazF homologues. Our work will guide future studies on the function of other M. tuberculosis MazF and MazE-MazF homologues, and will help delineate their physiological roles in M. tuberculosis stress responses and pathogenesis.