The importance of the tissue transglutaminase-fibronectin heterocomplex in the RGD-independent cell adhesion and fibronectin matrix deposition

Tissue transglutaminase (TG2) has been reported as a wound response protein. Once over-expressed by cells under stress such as during wound healing or following tissue damage, TG2 can be secreted and deposited into extracellular matrix, where it forms a heterocomplex (TG-FN) with the abundant matrix protein fibronectin (FN). A further cellular response elicited after tissue damage is that of matrix remodelling leading to the release of the Arg-Gly-Asp (RGD) containing matrix fragments by matrix matelloproteinases (MMPs). These peptides are able to block the interaction between integrin cell surface receptors and ECM proteins, leading to the loss of cell adhesion and ultimately Anoikis. This study provides a mechanism for TG2, as a stress-induced matrix protein, in protecting the cells from the RGD-dependent loss of cell adhesion and rescuing the cells from Anoikis. Mouse fibroblasts were used as a major model for this study, including different types of cell surface receptor knockout mouse embryonic fibroblasts (MEFs) (such as syndecan-4, a5, ß1 or ß3 integrins). In addition specific syndecan-2 targetting siRNAs, ß1 integrin and a4ß1 integrin functional blocking antibodies, and a specific targeting peptide against a5ß1 integrin A5-1 were used to investigate the involvement of these receptors in the RGD-independent cell adhesion on TG-FN. Crucial for TG-FN to compensate the RGD-independent cell adhesion and actin cytoskeleton formation is the direct interaction between the heparan sulfate chains of syndecan-4 and TG2, which elicits the inside-out signalling of a5ß1 integrin and the intracellular activation of syndecan-2 by protein kinase C a (PKCa). By using specific inhibitors, a cell-permeable inhibiting peptide and the detection of the phosphorylation sites for protein kinases and/or the translocation of PKCa via Western blotting, the activation of PKCa, focal adhesion kinase (FAK), ERK1/2 and Rho kinase (ROCK) were confirmed as downstream signalling molecules. Importantly, this study also investigated the influence of TG-FN on matrix turnover and demonstrated that TG-FN can restore the RGD-independent FN deposition process via an a5ß1 integrin and syndecan-4/2 co-signalling pathway linked by PKCa in a transamidating-independent manner. These data provide a novel function for TG2 in wound healing and matrix turnover which is a key event in a number of both physiological and pathological processes.

A prediction of outcomes: a psychological investigation into cognitive and affective development within the framework of adult literacy provision

This investigation seeks to explore the hypothesis, derived from observation and practice, that there is a strong relationship between the development of literacy skills and the growth of confidence in adult literacy students. Implicit in the developmental approach is the notion of progression towards some cognitive goal. Such a goal necessitates the establishment of a base line of existing attainment, together with subsequent assessment so that progress and development can be measured. The study includes an evaluation of existing formal and informal methods of initial and subsequent assessment and diagnosis available at the time for Adult Literacy Scheme Co-ordinators. Underlying the funding by Cheshire County Council for the project is the assumption that the results will be available for all practitioners and that the tools of measurement may be used by other Adult Literacy Co-ordinators in the County. It is intended, therefore, that this research should result in practical outcomes in which methods of assessment will involve active participation by students as well as by tutors, becoming part of the learning process. It is hypothesised that this kind of co-operation could lead ultimately to self-directed learning and student-independence. For the purposes of this research, a balance is attempted in the use of assessment tools, between standardised tests and informal methods. The study provides facts about students! reading habits; as well as their reading levels, their spelling levels, their handwriting, their writing skills and their writing habits. The study seeks to show the students' feelings towards education, their educational attainments and the type of school which they attended. The study also attempts to come to some measurement of those aspects of student personality which relate to confidence, by means of tests and questionnaires. The study concludes with an examination of the link between cognitive and affective progress.

Using organoclay to promote morphology refinement and co-continuity in high-density polyethylene/polyamide 6 blends - Effect of filler content and polymer matrix composition

We investigate the gradual changes of the microstructure of two blends of high-density polyethylene (HDPE) and polyamide 6 (PA6) at opposite composition filled with increasing amounts of an organomodified clay. The filler locates preferentially inside the polyamide phase, bringing about radical alterations in the micron-scale arrangement of the polymer phases. When the host polyamide represents the major constituent, a sudden reduction of the average sizes of the polyethylene droplets was observed upon addition of even low amounts of organoclay. A morphology refinement was also noticed at low filler contents when the particles distributes inside the minor phase. In this case, however, keep increasing the organoclay content eventually results in a high degree of PA6 phase continuity. Rheological analyses reveal that the filler loading at which the polyamide assembles in a continuous network corresponds to the critical threshold for its rheological transition from a liquid- to a gel-like behaviour, which is indicative of the structuring of the filler inside the host PA6. On the basis of this finding, a schematic mechanism is proposed in which the role of the filler in driving the space arrangement of the polymer phases is discussed. Finally, we show that the synergism between the reinforcing action of the filler and its ability to affect the blend microstructure can be exploited in order to enhance relevant technological properties of the materials, such as their high temperature structural integrity.

Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions

A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Effect of thermal and mechanical processing on tensile properties of powder formed 2124 aluminium and 2124 Al-SiC p metal matrix composite

The aging responses of 2124 Al-SiC p metal matrix composite (MMC) and unreinforced matrix alloy are studied and related to variations in tensile properties. The MMC is aged from Wo starting conditions: (i) stretched and naturally aged and (ii) re-solution treated. Accelerated aging occurs in both MMC conditions compared with unreinforced alloy. Tensile strengths and elastic moduli are improved in the MMC compared with the alloy, but ductility is reduced. Stretched MMC exhibits higher strength but lower ductility and modulus than re-solutioned MMC. The re-solutioned MMC fails by microvoid coalescence in low aging conditions, and by void nucleation and shear in high aging conditions. Failure of the stretched MMC initiates at the surface at specimen shoulders, illustrating the increased notch sensitivity of this condition, and propagates via a zigzag shear fracture mode. Zigzag facet size increases on gross aging. Particle fracture occurs during tensile failure, but also before testing as a result of the manufacturing process. © 1995 The Institute of Materials.

Bridging the gap between stylistic and cognitive approaches to authorship analysis using systemic functional linguistics and multidimensional analysis

In the present state of the art of authorship attribution there seems to be an opposition between two approaches: cognitive and stylistic methodologies. It is proposed in this article that these two approaches are complementary and that the apparent gap between them can be bridged using Systemic Functional Linguistics (SFL) and in particular some of its theoretical constructions, such as codal variation. This article deals with the theoretical explanation of why such a theory would solve the debate between the two approaches and shows how these two views of authorship attribution are indeed complementary. Although the article is fundamentally theoretical, two example experimental trials are reported to show how this theory can be developed into a workable methodology of doing authorship attribution. In Trial 1, a SFL analysis was carried out on a small dataset consisting of three 300-word texts collected from three different authors whose socio-demographic background matched across a number of parameters. This trial led to some conclusions about developing a methodology based on SFL and suggested the development of another trial, which might hint at a more accurate and useful methodology. In Trial 2, Biber's (1988) multidimensional framework is employed, and a final methodology of authorship analysis based on this kind of analysis is proposed for future research. © 2013, EQUINOX PUBLISHING.

An empirical examination of emotional and cognitive responses to threat appeals

Advertising and other forms of communications are often used by government bodies, non-government organisations, and other institutions to try to influence the population to either a) reduce some form of harmful behaviour (e.g. smoking, drunk- driving) or b) increase some more healthy behaviour (e.g. eating healthily). It is common for these messages to be predicated on the chances of some negative event occurring if the individual does not either a) stop the harmful behaviour, or b) start / increase the healthy behaviour. This design of communication is referred to by many names in the relevant literature, but for the purposes of this thesis, will be termed a ‘threat appeal’. Despite their widespread use in the public sphere, and concerted academic interest since the 1950s, the effectiveness of threat appeals in delivering their objective remains unclear in many ways. In a detailed, chronological and thematic examination of the literature, two assumptions are uncovered that have either been upheld despite little evidence to support them, or received limited attention at all, in the literature. Specifically, a) that threat appeal characteristics can be conflated with their intended responses, and b) that a threat appeal always and necessarily evokes a fear response in the subject. A detailed examination of these assumptions underpins this thesis. The intention is to take as a point of departure the equivocality of empirical results, and deliver a novel approach with the objective of reducing the confusion that is evident in existing work. More specifically, the present thesis frames cognitive and emotional responses to threat appeals as part of a decision about future behaviour. To further develop theory, a conceptual framework is presented that outlines the role of anticipated and anticipatory emotions, alongside subjective probabilities, elaboration and immediate visceral emotions, resultant from manipulation of the intrinsic message characteristics of a threat appeal (namely, message direction, message frame and graphic image). In doing so, the spectrum of relevant literature is surveyed, and used to develop a theoretical model which serves to integrate key strands of theory into a coherent model. In particular, the emotional and cognitive responses to the threat appeal manipulations are hypothesised to influence behaviour intentions and expectations pertaining to future behaviour. Using data from a randomised experiment with a sample of 681 participants, the conceptual model was tested using analysis of covariance. The results for the conceptual framework were encouraging overall, and also with regard to the individual hypotheses. In particular, empirical results showed clearly that emotional responses to the intrinsic message characteristics are not restricted to fear, and that different responses to threat appeals were clearly attributed to specific intrinsic message characteristics. In addition, the inclusion of anticipated emotions alongside cognitive appraisals in the framework generated interesting results. Specifically, immediate emotions did not influence key response variables related to future behaviour, in support of questioning the assumption of the prominent role of fear in the response process that is so prevalent in existing literature. The findings, theoretical and practical implications, limitations and directions for future research are discussed.

Organizational citizenship behavior and organizational commitment in Nepal

The present study examines the structure of organizational citizenship behavior (OCB) and its relation to organizational commitment in Nepal. Four-hundred and fifty employees of five Nepalese organizations filled out standardized questionnaires. Exploratory and confirmatory factor analyses revealed two factors of OCB, altruism and compliance, replicating Western models of extra-role behavior. Structural equation analysis showed a positive relation between affective and normative commitment on the one hand and both citizenship factors on the other. Continuance commitment was negatively related to compliance and unrelated to altruism. The findings thus confirmed the structure and usefulness of the concepts in an under-researched geographical area. Findings of the research are discussed within the Nepalese sociocultural context. © Blackwell Publishing Ltd with the Asian Association of Social Psychology and the Japanese Group Dynamics Association 2005.

Sharpening the edge of market driven intangibles and innovations

A review of the extant literature concludes that market-driven intangibles and innovations are increasingly considered to be the most critical firm-specific resources, but also finds a lack of elaboration of which types of these resources are most important. In this paper, we incorporate these observations into a conceptual model and link it to highly developed institutional settings for the model evaluation. From the point of view of firm revenue management, we can anticipate that performance advantages created through deployment of intellectual and relational capital in marketing and innovation are more likely to be superior. In essence, they constitute the integration of organisational intangibles both in cognitive and behavioural level to create an idiosyncratic combination for each firm. Our research findings show feasible paths for sharpening the edge of market-driven intangibles and innovations. We discuss the key results for research and practice.

Analysing the commitment - service quality relationship:a comparative study of retail banking call centres and branches

Adopting an internal marketing approach, this paper attempts to provide a deeper understanding of the organisational commitment—service quality relationship in the service context. This is done by empirically testing the relationships that the three components of organisational commitment (affective, continuance and normative) have with the service quality of customer-contact employees. The hypotheses were framed by critically reviewing the extant literature in the areas of services marketing and human resource management. A large sample comparative study was conducted on employees in call centres and branches of a major retail bank in UK. We explore the important question of how the three components of organisational commitment influence the employee-perceived service quality differently in call centres and in branches. The findings indicate that in branches, both affective commitment and continuance commitment have significant positive impact on service quality while in call centres, only affective commitment is found to affect service quality significantly. Having established the commitment—service quality relationship, the implications for designing internal marketing strategies are further discussed.

Comparing different approach and avoidance models of learning and personality in the prediction of work, university, and leadership outcomes

Jackson (2005) developed a hybrid model of personality and learning, known as the learning styles profiler (LSP) which was designed to span biological, socio-cognitive, and experiential research foci of personality and learning research. The hybrid model argues that functional and dysfunctional learning outcomes can be best understood in terms of how cognitions and experiences control, discipline, and re-express the biologically based scale of sensation-seeking. In two studies with part-time workers undertaking tertiary education (N=137 and 58), established models of approach and avoidance from each of the three different research foci were compared with Jackson's hybrid model in their predictiveness of leadership, work, and university outcomes using self-report and supervisor ratings. Results showed that the hybrid model was generally optimal and, as hypothesized, that goal orientation was a mediator of sensation-seeking on outcomes (work performance, university performance, leader behaviours, and counterproductive work behaviour). Our studies suggest that the hybrid model has considerable promise as a predictor of work and educational outcomes as well as dysfunctional outcomes.

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system:evidence from FMRI connectivity analysis

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.

A discussion of ethnographic research methods and their relevance for the translation process

In recent years, technologically advanced methodologies such as Translog have gained a lot of ground in translation process research. However, in this paper it will be argued that quantitative research methods can be supplemented by ethnographic qualitative ones so as to enhance our understanding of what underlies the translation process. Although translation studies scholars have sometimes applied an ethnographic approach to the study of translation, this paper offers a different perspective and considers the potential of ethnographic research methods for tapping cognitive and behavioural aspects of the translation process. A number of ethnographic principles are discussed and it is argued that process researchers aiming to understand translators’ perspectives and intentions, how these shape their behaviours, as well as how translators reflect on the situations they face and how they see themselves, would undoubtedly benefit from adopting an ethnographic framework for their studies on translation processes.