Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression

Objectives: Recently, pattern recognition approaches have been used to classify patterns of brain activity elicited by sensory or cognitive processes. In the clinical context, these approaches have been mainly applied to classify groups of individuals based on structural magnetic resonance imaging (MRI) data. Only a few studies have applied similar methods to functional MRI (fMRI) data. Methods: We used a novel analytic framework to examine the extent to which unipolar and bipolar depressed individuals differed on discrimination between patterns of neural activity for happy and neutral faces. We used data from 18 currently depressed individuals with bipolar I disorder (BD) and 18 currently depressed individuals with recurrent unipolar depression (UD), matched on depression severity, age, and illness duration, and 18 age- and gender ratio-matched healthy comparison subjects (HC). fMRI data were analyzed using a general linear model and Gaussian process classifiers. Results: The accuracy for discriminating between patterns of neural activity for happy versus neutral faces overall was lower in both patient groups relative to HC. The predictive probabilities for intense and mild happy faces were higher in HC than in BD, and for mild happy faces were higher in HC than UD (all p < 0.001). Interestingly, the predictive probability for intense happy faces was significantly higher in UD than BD (p = 0.03). Conclusions: These results indicate that patterns of whole-brain neural activity to intense happy faces were significantly less distinct from those for neutral faces in BD than in either HC or UD. These findings indicate that pattern recognition approaches can be used to identify abnormal brain activity patterns in patient populations and have promising clinical utility as techniques that can help to discriminate between patients with different psychiatric illnesses.

Dynamic causal modeling of load-dependent modulation of effective connectivity within the verbal working memory network

Neuroimaging studies have consistently shown that working memory (WM) tasks engage a distributed neural network that primarily includes the dorsolateral prefrontal cortex, the parietal cortex, and the anterior cingulate cortex. The current challenge is to provide a mechanistic account of the changes observed in regional activity. To achieve this, we characterized neuroplastic responses in effective connectivity between these regions at increasing WM loads using dynamic causal modeling of functional magnetic resonance imaging data obtained from healthy individuals during a verbal n-back task. Our data demonstrate that increasing memory load was associated with (a) right-hemisphere dominance, (b) increasing forward (i.e., posterior to anterior) effective connectivity within the WM network, and (c) reduction in individual variability in WM network architecture resulting in the right-hemisphere forward model reaching an exceedance probability of 99% in the most demanding condition. Our results provide direct empirical support that task difficulty, in our case WM load, is a significant moderator of short-term plasticity, complementing existing theories of task-related reduction in variability in neural networks. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

Regulation of IL-1β-induced NFκB by hydroxylases links key hypoxic and inflammatory signaling pathways

Hypoxia is a prominent feature of chronically inflamed tissues. Oxygen-sensing hydroxylases control transcriptional adaptation to hypoxia through the regulation of hypoxia-inducible factor (HIF) and nuclear factor ?B (NF-?B), both of which can regulate the inflammatory response. Furthermore, pharmacologic hydroxylase inhibitors reduce inflammation in multiple animal models. However, the underlying mechanism(s) linking hydroxylase activity to inflammatory signaling remains unclear. IL-1ß, a major proinflammatory cytokine that regulates NF-?B, is associated with multiple inflammatory pathologies. We demonstrate that a combination of prolyl hydroxylase 1 and factor inhibiting HIF hydroxylase isoforms regulates IL-1ß-induced NF-?B at the level of (or downstream of) the tumor necrosis factor receptor-associated factor 6 complex. Multiple proteins of the distal IL-1ß-signaling pathway are subject to hydroxylation and form complexes with either prolyl hydroxylase 1 or factor inhibiting HIF. Thus, we hypothesize that hydroxylases regulate IL-1ß signaling and subsequent inflammatory gene expression. Furthermore, hydroxylase inhibition represents a unique approach to the inhibition of IL-1ß-dependent inflammatory signaling.

The release of nitric oxide from S-nitrosothiols promotes angiogenesis

Free nitric oxide (NO) reacts with sulphydryl residues to form S-nitrosothiols, which act as NO reservoirs. We sought to determine whether thiol-preserving agents and antioxidants, such as dithiothreitol (DTT) and vitamin C, induce NO release from S-nitrosylated proteins in endothelial cell cultures to promote angiogenesis. NO release was measured directly in cell supernatants using a Sievers NO Analyser, and in vitro angiogenesis was assessed by quantifying capillary-like tube network formation of porcine aortic endothelial cells (PAEC) on growth factor-reduced Matrigel. Incubation of PAEC with DTT or vitamin C significantly increased NO release in a concentration-dependent manner. However, the nitric oxide synthase (NOS) inhibitors, L-NNA and L-NIO, had no effect on DTT- or vitamin C-induced NO release, and there was no concomitant increase in the phosphorylation of endothelial NOS at serine-1177 following DTT or vitamin C treatment. DTT and vitamin C increased capillary-like tube network formation by nine- and two-fold, respectively, and the addition of copper ions doubled the effect of vitamin C. Surprisingly, DTT maintained endothelial tube networks for up to one month under serum-free conditions, and selective inhibitors of guanylyl cyclase (ODQ) and PKG (KT-5823) blocked this, demonstrating the requirement of cyclic GMP and PKG in this process. Both DTT and vitamin C are capable of releasing sufficient NO from S-nitrosothiols to induce capillary morphogenesis. This study provides the first evidence that increased denitrosylation leads to increased bioavailability of NO, independent of NOS activity, to promote sustained angiogenesis.

Alumina-grafted SBA-15 as a high performance support for Pd-catalysed cinnamyl alcohol selective oxidation

Ultrathin alumina monolayers grafted onto an ordered mesoporous SBA-15 silica framework afford a composite catalyst support with unique structural properties and surface chemistry. Palladium nanoparticles deposited onto Al-SBA-15 via wet impregnation exhibit the high dispersion and surface oxidation characteristic of pure aluminas, in conjunction with the high active site densities characteristic of thermally stable, high-area mesoporous silicas. This combination confers significant rate enhancements in the aerobic selective oxidation (selox) of cinnamyl alcohol over Pd/Al-SBA-15 compared to mesoporous alumina or silica supports. Operando, liquid-phase XAS highlights the interplay between dissolved oxygen and the oxidation state of palladium nanoparticles dispersed over Al-SBA-15 towards on-stream reduction: ambient pressures of flowing oxygen are sufficient to hinder palladium oxide reduction to metal, enabling a high selox activity to be maintained, whereas rapid PdO reduction and concomitant catalyst deactivation occurs under static oxygen. Selectivity to the desired cinnamaldehyde product mirrors these trends in activity, with flowing oxygen minimising CO cleavage of the cinnamyl alcohol reactant to trans-β-methylstyrene, and of cinnamaldehyde decarbonylation to styrene. © 2013 Elsevier B.V.

An analysis of the characteristics of small and medium enterprises that use intellectual property

This report documents the creation of a major new database that links IP activity to all UK firms. It then analyses the characteristics of IP active firms, with a specific focus on SMEs.

Trade marks and performance in UK firms:evidence of Schumpeterian competition through innovation

This paper uses novel data on trade mark activity of UK manufacturing and service sector firms to investigate whether trade marks improve the profitability and productivity of firms. We first analyse Tobin`s q, the ratio of stock market value to book value of tangible assets. We then investigate the relationship between trade mark activity and productivity, using a value added production function. Finally we examine interactions between firms IP activity, to explore creative destruction and growth via innovation. We find trade marks are positively related to both Tobin`s q and to productivity. Also in the short run greater IP activity by other firms in the industry reduces the value added of the firm, but this same competitive pressure has later benefits via productivity growth, also reflected in higher stock market value. This describes the Schumpeterian process of competition through innovation, restraining profit margins while increasing product variety and quality.

Entrepreneurial intention and entrepreneurial behaviour:a social psychological perspective

Increasing the supply of entrepreneurs reduces unemployment and accelerates economic growth (Acs, 2006; Audretsch, 2007; Santarelli et el. 2009; Campbell, 1996; Carree & Thurik, 1996). The supply of entrepreneurs depends on the entrepreneurial intention and activity of the people (Kruger & Brazeal, 1994). Existing behavioural theories explain that entrepreneurial activity is an attitude driven process which is mediated by intention and regulated by behavioural control. These theories are: Theory of Planned Behaviour (Ajzen, 1991; 2002, 2012); Entrepreneurial Event Model (Shapiro & Shokol, 1982), and Social Cognitive Theory (Bandura, 1977; 1986; 2012). Meta-analysis of existing behavioural theories in different fields found that the theories are more effective to analyse behavioural intention and habitual behaviour, but less effective to analyse long-term and risky behaviour (McEachan et al., 2011). The objective of this dissertation is to improve entrepreneurship behaviour theory to advance our understanding of the determinants of the entrepreneurial intention and activity. To achieve this objective we asked three compelling questions in our research. These are: Firstly, why do differences exist in entrepreneurship among age groups. Secondly, how can we improve the theory to analyse entrepreneurial intention and behaviour? And, thirdly, is there any relationship between counterfactual or regretful thinking and entrepreneurial intention? We address these three questions in Chapters 2, 3 and 4 of the dissertation. Earlier studies have identified that there is an inverse U shaped relationship between age and entrepreneurship (Parker, 2004; Hart et al., 2004). In our study, we explain the reasons for this inverse U shape (Chapter 2). To analyse the reasons we use Cognitive Life Cycle theory and Disuse theory. We assume that the stage in the life cycle of an individual moderates the influence of opportunity identification and skill to start a business. In our study, we analyse the moderation effect in early stage entrepreneurship and in serial entrepreneurship. In Chapter 3, the limitations of existing psychological theories are discussed, and a competency value theory of entrepreneurship (CVTE) is proposed to overcome the limitations and extend existing theories. We use a ‘weighted competency’ variable instead of a ‘perceived behavioural control’ variable for the theory of planned behaviour (TPB) and self-efficacy variable for social cognitive theory. Weighted competency is the perceived competency ranking assigned by an individual for his total competencies to be an entrepreneur. The proposed theory was tested in a pilot survey in the UK and in a national adult population survey in a South Asian Country. The results show a significant relationship between competencies and entrepreneurial intention, and weighted competencies and entrepreneurial behaviour as per CVTE. To improve the theory further, in Chapter 4, we test the relationship between counterfactual thinking and entrepreneurial intention. Studies in cognitive psychology identify that ‘upward counterfactual thinking’ influences intention and behaviour (Epstude & Rose, 2008; Smallman & Roese, 2009). Upward counterfactual thinking is regretful thinking for missed opportunities of a problem. This study addresses the question of how an individual’s regretful thinking affects his or her future entrepreneurial career intention. To do so, we conducted a study among students in a business school in the UK, and we found that counterfactual thinking modifies the influence of attitude and opportunity identification in entrepreneurial career intention.

Cross-linking of cellular proteins by tissue transglutaminase during necrotic cell death:a mechanism for maintaining tissue integrity

Tissue transglutaminase (tTG) is a Ca2+-dependent enzyme which cross-links proteins via e(g-glutamyl)lysine bridges. There is increasing evidence that tTG is involved in wound repair and tissue stabilization, as well as in physiological mechanisms leading to cell death. To investigate the role of this enzyme in tissue wounding leading to loss of Ca2+ homoeostasis, we initially used a model involving electroporation to reproduce cell wounding under controlled conditions. Two cell models were used whereby tTG expression is regulated either by antisense silencing in ECV 304 cells or by using transfected Swiss 3T3 cells in which tTG expression is under the control of the tet regulatory system. Using these cells, loss of Ca2+ homoeostasis following electroporation led to a tTG-dependent formation of highly cross-linked proteinaceous shells from intracellular proteins. Formation of these structures is dependent on elevated intracellular Ca2+, but it is independent of intracellular proteases and is near maximal after only 20min post-wounding. Using labelled primary amines as an indicator of tTG activity within these 'wounded cells', we demonstrate that tTG modifies a wide range of proteins that are present in both the perinuclear and intranuclear spaces. The demonstration of entrapped DNA within these shell structures, which showed limited fragmentation, provides evidence that the high degree of transglutaminase cross-linking results in the prevention of DNA release, which may serve to dampen any subsequent inflammatory response. Comparable observations were shown when monolayers of cells were mechanically wounded by scratching. In this second model of cell wounding, redistribution of tTG activity to the extracellular matrix was also demonstrated, an effect which may serve to stabilize tissues post-trauma, and thus contribute to the maintenance of tissue integrity.

Risk factors for childhood myopia:findings from the NICER study

PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.

Stochasticity, periodicity and localized light structures in partially mode-locked fibre lasers

Physical systems with co-existence and interplay of processes featuring distinct spatio-temporal scales are found in various research areas ranging from studies of brain activity to astrophysics. The complexity of such systems makes their theoretical and experimental analysis technically and conceptually challenging. Here, we discovered that while radiation of partially mode-locked fibre lasers is stochastic and intermittent on a short time scale, it exhibits non-trivial periodicity and long-scale correlations over slow evolution from one round-trip to another. A new technique for evolution mapping of intensity autocorrelation function has enabled us to reveal a variety of localized spatio-temporal structures and to experimentally study their symbiotic co-existence with stochastic radiation. Real-time characterization of dynamical spatio-temporal regimes of laser operation is set to bring new insights into rich underlying nonlinear physics of practical active- and passive-cavity photonic systems.

On a Virtual Learning Environment

Education in the Information Society is based on asynchronism in time and space, interactivity and virtual restructuring of the educational space. One way to implement such a model of training is web-based - use of the WWW as a virtual environment to access educational materials or to organize the learning process. This work presents a virtual learning environment (VLE) developed for students and made up of modules of dynamically changing content implemented by authorized users. The aim is, through advanced technology for e-learning, testing and self-testing to stimulate students’ activity to focus their potential on the acquisition of the necessary knowledge, skills and competences. The VLE was developed under the Human Resources Development Operational Programme.

Teachers' perceptions of the usefulness of Individual Education Plans (IEP)

Since 1997 federal special education policy mandated that all classroom teachers take part in planning and implementation of Individualized Education Plans (IEP) for students with disabilities. This legislation has given teachers new responsibilities because it requires greater participation in the IEP process. The purpose of this study was to examine teachers' perceptions of the usefulness of Individualized Education Plans (IEP). ^ Eighty seven certified Miami-Dade County Public School teachers, 60 general education teachers and 27 special education teachers were surveyed using an updated version of Rheams' (1989) The Teacher Perceptions of the Usefulness of IEPs. Subjects completed a survey form containing a demographic cover page, 18 Likert-scale statements and 3 open ended questions. This study looked at differences in perceptions by teacher group affiliation (general and special), grade level taught (elementary and secondary), and years of experience (<=5 and >5 years). The dependent variables were teacher preparedness; feasibility of IEP implementation; relevancy of IP to classroom instruction; and legal, professional and personal accountability with regard to the IEP. ^ Results of the Multivariate Analysis of Variance (MANOVA) revealed that (a) special education teachers held a more positive perception of overall IEP usefulness than general education teachers, (b) special educators held more positive perceptions concerning issues of feasibility and preparedness, (c) elementary level teachers viewed the IEP more positively than secondary level teachers, specifically in the areas of preparedness and feasibility. ^ Findings of this study indicate that general and secondary educators have not embraced the legislation and incorporated it into their planning and instruction. These findings provide policymakers, institutions of higher education, and school administrators with insight as to how to better translate policy into classroom instructional practice. Consideration should be given to implementing (a) honest communication and shared decision making with regard to IEP directed curriculum and instruction, (b) updated pre and in-service IEP development and implementation training, and (c) opportunities for collaboration and increased plan time, especially on the secondary level. ^

Testing the Efficacy of Panax ginseng Extract as a Novel Anti-Quorum Sensing Agent

Quorum sensing (QS) is the phenomenon by which microorganisms regulate gene expression in response to cell-population density. These microorganisms synthesize and secrete small molecules known as autoinducers that increase in concentration as a function of cell density. Once the cell detects the minimal threshold concentration of an autoinducer, the gene expression is altered accordingly. Although the cellular circuitry responding to QS is relatively conserved, the cellular processes regulated by QS, for example are conjugation, motility, sporulation, biofilm formation and production of virulence factors importamt for infection. Since many pathogens have developed resistance to available antibiotics, novel therapies are required to further treat these pathogens. Inhibitors of QS are potential therapeutic candidates since they would inhibit virulence without selecting for antibiotic resistant strains. Previous studies have shown that the Chinese herb Panax ginseng contains compounds that inhibit QS activity. To further characterize this activity, a highly sensitive quantitative liquid assay was developed using a Chromobacterium violaceum AHL mutant, CV026 as a biomonitor strain. After confirmation that P. ginseng aqueous extracts had anti-QS activity, the extract was fractionated on a reverse phase C18 Sep Pak column. Most anti-QS activity was present in the flow through, and compounds eluted with ten percent acetonitrile in water antibacterial activity. We thus conclude that P. ginseng has anti-QS activity and the active compound is water soluble. Compounds from P. ginseng, could be used as a lead structure to design compound with higher anti-QS activity for therapeutic treatments.

Multicultural Literacy in Education: Meeting the Objectives of the Florida Sunshine State Standards

The purpose of this paper is to show how incorporating multicultural literacy in education can meet the Florida Sunshine State Standards to promote a more equitable approach to classroom discourse and a qualitative teacher-facilitated learning environment for students who reflect a multicultural and global community.