In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex

Matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) contribute to the pathophysiology of bacterial meningitis. To date, MMP-inhibitors studied in models of meningitis were compromised by their hydrophobic nature. We investigated the pharmacokinetics and the effect of TNF484, a water-soluble hydroxamate-based inhibitor of MMP and TACE, on disease parameters and brain damage in a neonatal rat model of pneumococcal meningitis. At 1 mg/kg q6h TNF484 reduced soluble TNF-alpha and the collagen degradation product hydroxyproline in the cerebrospinal fluid. Clinically, TNF484 attenuated the incidence of seizures and was neuroprotective in the cortex. Water-soluble MMP-inhibitors may hold promise in the therapy of bacterial meningitis.

Oil viscosity from experiments and model calculations

Five frequently-used models were chosen and evaluated to calculate the viscosity of the mixed oil. Totally twenty mixed oil samples were prepared with different ratios of light to crude oil from different oil wells but the same oil field. The viscosities of the mixtures under the same shear rates of 10 s**-1 were measured using a rotation viscometer at the temperatures ranging from 30°C to 120°C. After comparing all of the experimental data with the corresponding model values, the best one of the five models for this oil field was determined. Using the experimental data, one model with a better accuracy than the existing models was developed to calculate the viscosity of mixed oils. Another model was derived to predict the viscosity of mixed oils at different temperatures and different values of mixing ratio of light to heavy oil.

Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex.

Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation. These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton. The molecular basis for these interactions and their hierarchy of interaction remain controversial. We demonstrate a direct interaction between F-actin and alpha (E)-catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or beta-catenin. Sedimentation assays and direct visualization by transmission electron microscopy reveal that alpha 1(E)-catenin binds and bundles F-actin in vitro with micromolar affinity at a catenin/G-actin monomer ratio of approximately 1:7 (mol/mol). Recombinant human beta-catenin can simultaneously bind to the alpha-catenin/actin complex but does not bind actin directly. Recombinant fragments encompassing the amino-terminal 228 residues of alpha 1(E)-catenin or the carboxyl-terminal 447 residues individually bind actin in cosedimentation assays with reduced affinity compared with the full-length protein, and neither fragment bundles actin. Except for similarities to vinculin, neither region contains sequences homologous to established actin-binding proteins. Collectively these data indicate that alpha 1 (E)-catenin is a novel actin-binding and -bundling protein and support a model in which alpha 1(E)-catenin is responsible for organizing and tethering actin filaments at the zones of E-cadherin-mediated cell-cell contact.

Best Alternatives to Cronbach's Alpha Reliability in Realistic Conditions: Congeneric and Asymmetrical Measurements

The Cronbach's alpha is the most widely used method for estimating internal consistency reliability. This procedure has proved very resistant to the passage of time, even if its limitations are well documented and although there are better options as omega coefficient or the different versions of glb, with obvious advantages especially for applied research in which the ítems differ in quality or have skewed distributions. In this paper, using Monte Carlo simulation, the performance of these reliability coefficients under a one-dimensional model is evaluated in terms of skewness and no tau-equivalence. The results show that omega coefficient is always better choice than alpha and in the presence of skew items is preferable to use omega and glb coefficients even in small samples.

Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning

Caveolae are an abundant feature of many animal cells. However, the exact function of caveolae remains unclear. We have used the zebrafish, Danio rerio, as a system to understand caveolae function focusing on the muscle-specific caveolar protein, caveolin-3 (Cav3). We have identified caveolin-1 (alpha and beta), caveolin-2 and Cav3 in the zebrafish. Zebrafish Cav3 has 72% identity to human CAV3, and the amino acids altered in human muscle diseases are conserved in the zebrafish protein. During embryonic development, cav3 expression is apparent by early segmentation stages in the first differentiating muscle precursors, the adaxial cells and slightly later in the notochord. cav3 expression appears in the somites during mid-segmentation stages and then later in the pectoral fins and facial muscles. Cav3 and caveolae are located along the entire sarcolemma of late stage embryonic muscle fibers, whereas beta-dystroglycan is restricted to the muscle fiber ends. Down-regulation of Cav3 expression causes gross muscle abnormalities and uncoordinated movement. Ultrastructural analysis of isolated muscle fibers reveals defects in myoblast fusion and disorganized myofibril and membrane systems. Expression of the zebrafish equivalent to a human muscular dystrophy mutant, CAV3P104L, causes severe disruption of muscle differentiation. In addition, knockdown of Cav3 resulted in a dramatic up-regulation of eng1a expression resulting in an increase in the number of muscle pioneer-like cells adjacent to the notochord. These studies provide new insights into the role of Cav3 in muscle development and demonstrate its requirement for correct intracellular organization and myoblast fusion.

Fast and slowly evolving vector solitons in mode-locked fibre lasers

We report on a new vector model of an erbium-doped fibre laser mode locked with carbon nanotubes. This model goes beyond the limitations of the previously used models based on either coupled nonlinear Schrödinger or Ginzburg-Landau equations. Unlike the previous models, it accounts for the vector nature of the interaction between an optical field and an erbium-doped active medium, slow relaxation dynamics of erbium ions, linear birefringence in a fibre, linear and circular birefringence of a laser cavity caused by in-cavity polarization controller and light-induced anisotropy caused by elliptically polarized pump field. Interplay of aforementioned factors changes coherent coupling of two polarization modes at a long time scale and so results in a new family of vector solitons (VSs) with fast and slowly evolving states of polarization. The observed VSs can be of interest in secure communications, trapping and manipulation of atoms and nanoparticles, control of magnetization in data storage devices and many other areas.

Quark model with chiral-symmetry breaking and confinement in the Covariant Spectator Theory

We propose a model for the quark-antiquark interaction in Minkowski space using the Covariant Spectator Theory. We show that with an equal-weighted scalar-pseudoscalar structure for the confining part of our interaction kernel the axial-vector Ward-Takahashi identity is preserved and our model complies with the Adler-zero constraint for π-π-scattering imposed by chiral symmetry.

Theorising a model for teaching and assessing reflective learning in higher education

The importance of reflection in higher education, and across disciplinary fields is widely recognised; it is generally included in university graduate attributes, professional standards and program objectives. Furthermore, reflection is commonly embedded into assessment requirements in higher education subjects, often without necessary scaffolding or clear expectations for students. Despite the rhetoric around the importance of reflection for ongoing learning, there is scant literature on any systematic, developmental approach to teaching reflective learning across higher education programs/courses. Given that professional or academic reflection is not intuitive, and requires specific pedagogic intervention to do well, a program/course-wide approach is essential. This paper draws on current literature to theorise a new, transferable and customisable model for teaching and assessing reflective learning across higher education, which foregrounds and explains the pedagogic field of higher education as a multi-dimensional space. We argue that explicit and strategic pedagogic intervention, supported by dynamic resources, is necessary for successful, broad-scale approaches to reflection in higher education.

Quantification of particle emission characteristics and development of an emission model for use in transport microenvironments affected by traffic emissions

Vehicle emitted particles are of significant concern based on their potential to influence local air quality and human health. Transport microenvironments usually contain higher vehicle emission concentrations compared to other environments, and people spend a substantial amount of time in these microenvironments when commuting. Currently there is limited scientific knowledge on particle concentration, passenger exposure and the distribution of vehicle emissions in transport microenvironments, partially due to the fact that the instrumentation required to conduct such measurements is not available in many research centres. Information on passenger waiting time and location in such microenvironments has also not been investigated, which makes it difficult to evaluate a passenger’s spatial-temporal exposure to vehicle emissions. Furthermore, current emission models are incapable of rapidly predicting emission distribution, given the complexity of variations in emission rates that result from changes in driving conditions, as well as the time spent in driving condition within the transport microenvironment. In order to address these scientific gaps in knowledge, this work conducted, for the first time, a comprehensive statistical analysis of experimental data, along with multi-parameter assessment, exposure evaluation and comparison, and emission model development and application, in relation to traffic interrupted transport microenvironments. The work aimed to quantify and characterise particle emissions and human exposure in the transport microenvironments, with bus stations and a pedestrian crossing identified as suitable research locations representing a typical transport microenvironment. Firstly, two bus stations in Brisbane, Australia, with different designs, were selected to conduct measurements of particle number size distributions, particle number and PM2.5 concentrations during two different seasons. Simultaneous traffic and meteorological parameters were also monitored, aiming to quantify particle characteristics and investigate the impact of bus flow rate, station design and meteorological conditions on particle characteristics at stations. The results showed higher concentrations of PN20-30 at the station situated in an open area (open station), which is likely to be attributed to the lower average daily temperature compared to the station with a canyon structure (canyon station). During precipitation events, it was found that particle number concentration in the size range 25-250 nm decreased greatly, and that the average daily reduction in PM2.5 concentration on rainy days compared to fine days was 44.2 % and 22.6 % at the open and canyon station, respectively. The effect of ambient wind speeds on particle number concentrations was also examined, and no relationship was found between particle number concentration and wind speed for the entire measurement period. In addition, 33 pairs of average half-hourly PN7-3000 concentrations were calculated and identified at the two stations, during the same time of a day, and with the same ambient wind speeds and precipitation conditions. The results of a paired t-test showed that the average half-hourly PN7-3000 concentrations at the two stations were not significantly different at the 5% confidence level (t = 0.06, p = 0.96), which indicates that the different station designs were not a crucial factor for influencing PN7-3000 concentrations. A further assessment of passenger exposure to bus emissions on a platform was evaluated at another bus station in Brisbane, Australia. The sampling was conducted over seven weekdays to investigate spatial-temporal variations in size-fractionated particle number and PM2.5 concentrations, as well as human exposure on the platform. For the whole day, the average PN13-800 concentration was 1.3 x 104 and 1.0 x 104 particle/cm3 at the centre and end of the platform, respectively, of which PN50-100 accounted for the largest proportion to the total count. Furthermore, the contribution of exposure at the bus station to the overall daily exposure was assessed using two assumed scenarios of a school student and an office worker. It was found that, although the daily time fraction (the percentage of time spend at a location in a whole day) at the station was only 0.8 %, the daily exposure fractions (the percentage of exposures at a location accounting for the daily exposure) at the station were 2.7% and 2.8 % for exposure to PN13-800 and 2.7% and 3.5% for exposure to PM2.5 for the school student and the office worker, respectively. A new parameter, “exposure intensity” (the ratio of daily exposure fraction and the daily time fraction) was also defined and calculated at the station, with values of 3.3 and 3.4 for exposure to PN13-880, and 3.3 and 4.2 for exposure to PM2.5, for the school student and the office worker, respectively. In order to quantify the enhanced emissions at critical locations and define the emission distribution in further dispersion models for traffic interrupted transport microenvironments, a composite line source emission (CLSE) model was developed to specifically quantify exposure levels and describe the spatial variability of vehicle emissions in traffic interrupted microenvironments. This model took into account the complexity of vehicle movements in the queue, as well as different emission rates relevant to various driving conditions (cruise, decelerate, idle and accelerate), and it utilised multi-representative segments to capture the accurate emission distribution for real vehicle flow. This model does not only helped to quantify the enhanced emissions at critical locations, but it also helped to define the emission source distribution of the disrupted steady flow for further dispersion modelling. The model then was applied to estimate particle number emissions at a bidirectional bus station used by diesel and compressed natural gas fuelled buses. It was found that the acceleration distance was of critical importance when estimating particle number emission, since the highest emissions occurred in sections where most of the buses were accelerating and no significant increases were observed at locations where they idled. It was also shown that emissions at the front end of the platform were 43 times greater than at the rear of the platform. The CLSE model was also applied at a signalled pedestrian crossing, in order to assess increased particle number emissions from motor vehicles when forced to stop and accelerate from rest. The CLSE model was used to calculate the total emissions produced by a specific number and mix of light petrol cars and diesel passenger buses including 1 car travelling in 1 direction (/1 direction), 14 cars / 1 direction, 1 bus / 1 direction, 28 cars / 2 directions, 24 cars and 2 buses / 2 directions, and 20 cars and 4 buses / 2 directions. It was found that the total emissions produced during stopping on a red signal were significantly higher than when the traffic moved at a steady speed. Overall, total emissions due to the interruption of the traffic increased by a factor of 13, 11, 45, 11, 41, and 43 for the above 6 cases, respectively. In summary, this PhD thesis presents the results of a comprehensive study on particle number and mass concentration, together with particle size distribution, in a bus station transport microenvironment, influenced by bus flow rates, meteorological conditions and station design. Passenger spatial-temporal exposure to bus emitted particles was also assessed according to waiting time and location along the platform, as well as the contribution of exposure at the bus station to overall daily exposure. Due to the complexity of the interrupted traffic flow within the transport microenvironments, a unique CLSE model was also developed, which is capable of quantifying emission levels at critical locations within the transport microenvironment, for the purpose of evaluating passenger exposure and conducting simulations of vehicle emission dispersion. The application of the CLSE model at a pedestrian crossing also proved its applicability and simplicity for use in a real-world transport microenvironment.

Spot the differences in traditional and social entrepreneurial intention : highlighting the role of human and social capital

There is general agreement in the scientific community that entrepreneurship plays a central role in the growth and development of an economy in rapidly changing environments (Acs & Virgill 2010). In particular, when business activities are regarded as a vehicle for sustainable growth at large, that goes beyond mere economic returns of singular entities, encompassing also social problems and heavily relying on collaborative actions, then we more precisely fall into the domain of ‘social entrepreneurship’(Robinson et al. 2009). In the entrepreneurship literature, prior studies demonstrated the role of intentionality as the best predictor of planned behavior (Ajzen 1991), and assumed that the intention to start a business derives from the perception of desirability and feasibility and from a propensity to act upon an opportunity (Fishbein & Ajzen 1975). Recognizing that starting a business is an intentional act (Krueger et al. 2000) and entrepreneurship is a planned behaviour (Katz & Gartner 1988), models of entrepreneurial intentions have substantial implications for intentionality research in entrepreneurship. The purpose of this paper is to explore the emerging practice of social entrepreneurship by comparing the determinants of entrepreneurial intention in general versus those leading to startups with a social mission. Social entrepreneurial intentions clearly merit to be investigated given that the opportunity identification process is an intentional process not only typical of for profit start-ups, and yet there is a lack of research examining opportunity recognition in social entrepreneurship (Haugh 2005). The key argument is that intentionality in both traditional and social entrepreneurs during the decision-making process of new venture creation is influenced by an individual's perceptions toward opportunities (Fishbein & Ajzen 1975). Besides opportunity recognition, at least two other aspects can substantially influence intentionality: human and social capital (Davidsson, 2003). This paper is set to establish if and to what extent the social intentions of potential entrepreneurs, at the cognitive level, are influenced by opportunities recognition, human capital, and social capital. By applying established theoretical constructs, the paper draws comparisons between ‘for-profit’ and ‘social’ intentionality using two samples of students enrolled in Economy and Business Administration at the University G. d’Annunzio in Pescara, Italy. A questionnaire was submitted to 310 potential entrepreneurs to test the robustness of the model. The collected data were used to measure the theoretical constructs of the paper. Reliability of the multi-item scale for each dimension was measured using Cronbach alpha, and for all the dimensions measures of reliability are above 0.70. We empirically tested the model using structural equation modeling with AMOS. The results allow us to empirically contribute to the argument regarding the influence of human and social cognitive capital on social and non-social entrepreneurial intentions. Moreover, we highlight the importance for further researchers to look deeper into the determinants of traditional and social entrepreneurial intention so that governments can one day define better polices and regulations that promote sustainable businesses with a social imprint, rather than inhibit their formation and growth.

Extending and validating the is-impact model in Saudi Arabia : accounting for computer network quality

Organizations from every industry sector seek to enhance their business performance and competitiveness through the deployment of contemporary information systems (IS), such as Enterprise Systems (ERP). Investments in ERP are complex and costly, attracting scrutiny and pressure to justify their cost. Thus, IS researchers highlight the need for systematic evaluation of information system success, or impact, which has resulted in the introduction of varied models for evaluating information systems. One of these systematic measurement approaches is the IS-Impact Model introduced by a team of researchers at Queensland University of technology (QUT) (Gable, Sedera, & Chan, 2008). The IS-Impact Model is conceptualized as a formative, multidimensional index that consists of four dimensions. Gable et al. (2008) define IS-Impact as "a measure at a point in time, of the stream of net benefits from the IS, to date and anticipated, as perceived by all key-user-groups" (p.381). The IT Evaluation Research Program (ITE-Program) at QUT has grown the IS-Impact Research Track with the central goal of conducting further studies to enhance and extend the IS-Impact Model. The overall goal of the IS-Impact research track at QUT is "to develop the most widely employed model for benchmarking information systems in organizations for the joint benefit of both research and practice" (Gable, 2009). In order to achieve that, the IS-Impact research track advocates programmatic research having the principles of tenacity, holism, and generalizability through extension research strategies. This study was conducted within the IS-Impact Research Track, to further generalize the IS-Impact Model by extending it to the Saudi Arabian context. According to Hofsted (2012), the national culture of Saudi Arabia is significantly different from the Australian national culture making the Saudi Arabian culture an interesting context for testing the external validity of the IS-Impact Model. The study re-visits the IS-Impact Model from the ground up. Rather than assume the existing instrument is valid in the new context, or simply assess its validity through quantitative data collection, the study takes a qualitative, inductive approach to re-assessing the necessity and completeness of existing dimensions and measures. This is done in two phases: Exploratory Phase and Confirmatory Phase. The exploratory phase addresses the first research question of the study "Is the IS-Impact Model complete and able to capture the impact of information systems in Saudi Arabian Organization?". The content analysis, used to analyze the Identification Survey data, indicated that 2 of the 37 measures of the IS-Impact Model are not applicable for the Saudi Arabian Context. Moreover, no new measures or dimensions were identified, evidencing the completeness and content validity of the IS-Impact Model. In addition, the Identification Survey data suggested several concepts related to IS-Impact, the most prominent of which was "Computer Network Quality" (CNQ). The literature supported the existence of a theoretical link between IS-Impact and CNQ (CNQ is viewed as an antecedent of IS-Impact). With the primary goal of validating the IS-Impact model within its extended nomological network, CNQ was introduced to the research model. The Confirmatory Phase addresses the second research question of the study "Is the Extended IS-Impact Model Valid as a Hierarchical Multidimensional Formative Measurement Model?". The objective of the Confirmatory Phase was to test the validity of IS-Impact Model and CNQ Model. To achieve that, IS-Impact, CNQ, and IS-Satisfaction were operationalized in a survey instrument, and then the research model was assessed by employing the Partial Least Squares (PLS) approach. The CNQ model was validated as a formative model. Similarly, the IS-Impact Model was validated as a hierarchical multidimensional formative construct. However, the analysis indicated that one of the IS-Impact Model indicators was insignificant and can be removed from the model. Thus, the resulting Extended IS-Impact Model consists of 4 dimensions and 34 measures. Finally, the structural model was also assessed against two aspects: explanatory and predictive power. The analysis revealed that the path coefficient between CNQ and IS-Impact is significant with t-value= (4.826) and relatively strong with â = (0.426) with CNQ explaining 18% of the variance in IS-Impact. These results supported the hypothesis that CNQ is antecedent of IS-Impact. The study demonstrates that the quality of Computer Network affects the quality of the Enterprise System (ERP) and consequently the impacts of the system. Therefore, practitioners should pay attention to the Computer Network quality. Similarly, the path coefficient between IS-Impact and IS-Satisfaction was significant t-value = (17.79) and strong â = (0.744), with IS-Impact alone explaining 55% of the variance in Satisfaction, consistent with results of the original IS-Impact study (Gable et al., 2008). The research contributions include: (a) supporting the completeness and validity of IS-Impact Model as a Hierarchical Multi-dimensional Formative Measurement Model in the Saudi Arabian context, (b) operationalizing Computer Network Quality as conceptualized in the ITU-T Recommendation E.800 (ITU-T, 1993), (c) validating CNQ as a formative measurement model and as an antecedent of IS Impact, and (d) conceptualizing and validating IS-Satisfaction as a reflective measurement model and as an immediate consequence of IS Impact. The CNQ model provides a framework to perceptually measure Computer Network Quality from multiple perspectives. The CNQ model features an easy-to-understand, easy-to-use, and economical survey instrument.

Detection of mRNA levels for the estrogen alpha, estrogen beta and androgen nuclear receptor genes in archival breast cancer tissue

Previous studies in our laboratory have shown association of nuclear receptor expression and histological breast cancer grade. To further investigate these findings, it was the objective of this study to determine if expression levels of the estrogen alpha, estrogen beta and androgen nuclear receptor genes varied in different breast cancer grades. RNA extracted from paraffin embedded archival breast tumour tissue was converted into cDNA and cDNA underwent PCR to enable quantitation of mRNA expression. Expression data was normalised against the 18S ribosomal gene multiplex and analysed using ANOVA. Analysis indicated a significant alteration of expression for the androgen receptor in different cancer grades (P=0.014), as well as in tissues that no longer possess estrogen receptor alpha proteins (P=0.025). However, expression of estrogen receptors alpha and beta did not vary significantly with cancer grade (P=0.057 and 0.622, respectively). Also, the expression of estrogen receptor alpha or beta did not change, regardless of the presence of estrogen receptor alpha protein in the tissue (P=0.794 and 0.716, respectively). Post-hoc tests indicate that the expression of the androgen receptor is increased in estrogen receptor negative tissue as well as in grade 2 and grade 3 tumours, compared to control tissue. This increased expression in late stage breast tumours may have implications to the treatment of breast tumours, particularly those lacking expression of other nuclear receptor genes.

"You’ve modelled and now what?" : Exploring determinants of process model re-use

Business process modelling as a practice and research field has received great attention over recent years. Organizations invest significantly into process modelling in terms of training, tools, capabilities and resources. The return on this investment is a function of process model re-use, which we define as the recurring use of process models to support organizational work tasks. While prior research has examined re-use as a design principle, we explore re-use as a behaviour, because evidence suggest that analysts’ re-use of process models is indeed limited. In this paper we develop a two-stage conceptualization of the key object-, behaviour- and socioorganization-centric factors explaining process model re-use behaviour. We propose a theoretical model and detail implications for its operationalization and measurement. Our study can provide significant benefits to our understanding of process modelling and process model use as key practices in analysis and design.

Process model comprehension : the effects of cognitive abilities, learning style, and strategy

Process models are used to convey semantics about business operations that are to be supported by an information system. A wide variety of professionals is targeted to use such models, including people who have little modeling or domain expertise. We identify important user characteristics that influence the comprehension of process models. Through a free simulation experiment, we provide evidence that selected cognitive abilities, learning style, and learning strategy influence the development of process model comprehension. These insights draw attention to the importance of research that views process model comprehension as an emergent learning process rather than as an attribute of the models as objects. Based on our findings, we identify a set of organizational intervention strategies that can lead to more successful process modeling workshops.