Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

An examination of the development of LTL hub-and-spoke freight distribution systems

Over recent years, hub-and-spoke distribution techniques have attracted widespread research attention. Despite there being a growing body of literature in this area there is less focus on the spoke-terminal element of the hub-and-spoke system as being a key component in the overall service received by the end-user. Current literature is highly geared towards discussing bulk optimization of freight units rather than to the more discrete and individualistic profile characteristics of shared-user Less-than-truckload (LTL) freight. In this paper, a literature review is presented to review the role hub-and-spoke systems play in meeting multi-profile customer demands, particularly in developing sectors with more sophisticated needs, such as retail. The paper also looks at the use of simulation technology as a suitable tool for analyzing spoke-terminal operations within developing hub-and spoke systems.

A taxonomy of measures for consumer-based brand equity:drawing on the views of managers in Europe

Purpose: The purpose of this paper is to identify the components of consumer-based brand equity from the perspective of experts in brand management in the UK, Germany and Greece. Design/methodology/approach: Data were collected from semi-structured interviews with senior brand consultants and managers, five in the UK, five in Germany and five in Greece. Findings: The findings suggested four categories of measures which can be used to define brand equity. These are the consumers' understanding of brand characteristics; consumers' brand evaluation; consumers' affective response towards the brand; and consumers' behaviour towards the brand. Specific dimensions are identified as indicators of each category. Research limitations/implications: Although the focus of this study is Europe, data were only collected from the UK, Germany and Greece, countries representing three of the five European cultural clusters. The resultant taxonomy adds to the fragmented literature on brand equity measurement by proposing four categories to gauge brand equity. Practical implications: The suggested taxonomy provides indicators of a framework managers could use when assessing brand equity. Originality/value: There is little agreement on what constitutes brand equity and therefore measures of brand equity are fragmented. To date, the views of practicing managers have not been taken into account in research. This paper draws on the views of practitioners and academics to suggest a taxonomy of categories of measures for brand equity. © Emerald Group Publishing Limited.

A taxonomy of heterogeneity and dynamics in particle swarm optimisation

We propose a taxonomy for heterogeneity and dynamics of swarms in PSO, which separates the consideration of homogeneity and heterogeneity from the presence of adaptive and non-adaptive dynamics, both at the particle and swarm level. It thus supports research into the separate and combined contributions of each of these characteristics. An analysis of the literature shows that most recent work has focussed on only parts of the taxonomy. Our results agree with prior work that both heterogeneity and dynamics are useful. However while heterogeneity does typically improve PSO, this is often dominated by the improvement due to dynamics. Adaptive strategies used to generate heterogeneity may end up sacrificing the dynamics which provide the greatest performance increase. We evaluate exemplar strategies for each area of the taxonomy and conclude with recommendations.

The management of industrial development in Kuwait

Thesis was water damaged in store, retrieved for use but may still show signs of damage. Unable to scan to make available online.

Procedure of Formalization of the Indices of Banks’ Stable Functioning in Comparative Estimates of Their Development

The advisability of analyzing the banks liquidity and profitability as the key factor when building the comparative estimate of their functioning is considered. The procedure of formal description of the bank stable functioning indices is substantiated. Fuzzy interpretation of the bank management efficiency estimation is offered. The possibility to formalize the bank functioning estimates on the basis of the corresponding fuzzy set levels hierarchy is analyzed. The comparative estimate of different bank systems functioning is given.

Reluctant donors? The Europeanization of international development policies in the New Member States

The European Union (EU) played an instrumental role in re-starting the international development policies in central and eastern European Member States, but questions remain about how far this policy area has been Europeanized since accession. Focusing on the Czech Republic, Hungary, Poland and Slovakia, this article investigates why the new donors have been reluctant to adopt the EU's development acquis more fully. The article traces the socialization processes offered by the EU's development policy rule-making and subsequent national rule implementation. The conclusions reveal three reasons why socialization has been weak: perceptions among the new Member States on the procedural legitimacy of the development acquis; low domestic resonance with the development acquis; and inconsistencies in the activities of norm entrepreneurs. The article contributes to our understanding of development policy in the EU – particularly how decision-making takes place within the Council and its working groups post-enlargement.

Determinants of civil society influence:the case of international development and humanitarian NGOs in the Czech Republic and Hungary

Accession to the EU has had ambiguous effects on civil society organizations (CSOs) in the East Central European countries. A general observation is that accession has not led to the systematic empowerment of CSOs in terms of growing influence on national policy making. This article investigates the determinants of successful CSO advocacy by looking at international development and humanitarian NGOs (NGDOs) in the Czech Republic and Hungary. Reforms in the past decade in the Czech Republic have created an international development policy largely in line with NGDO interests, while Hungary’s ministry of foreign affairs seems to have been unresponsive to reform demands from civil society. The article argues that there is clear evidence of NGDO influence in the Czech Republic on international development policy, which is because of the fact that Czech NGDOs have been able solve problems of collective actions, while the Hungarian NGDO sector remains fragmented. They also have relatively stronger capacities, can rely on greater public support and can thus present more legitimate demands towards their government.

The Conception of Creation of Integrated Development Environment for Computer Training Systems

The various questions of creation of integrated development environment for computer training systems are considered in the given paper. The information technologies that can be used for creation of the integrated development environment are described. The different didactic aspects of realization of such systems are analyzed. The ways to improve the efficiency and quality of learning process with computer training systems for distance education are pointed.

Direct observation of morphological development during the spin-coating of polystyrene-poly(methyl methacrylate) polymer blends

We present results of the direct observation, in real-space, of the phase separation of high molecular weight polystyrene and poly(methyl methacrylate) from ortho-xylene using our newly developed technique of high speed stroboscopic interference microscopy. Taking a fixed concentration (3 wt % in o-xylene) at a fixed composition (1:4 by weight) and by varying the rotational rate during the spin-coating process, we are able to observe the formation of a range of phase separated bicontinuous morphologies of differing length-scales. Importantly, we are able to show that the mechanism by which the final phase separated structure is formed is through domain coarsening when rich in solvent, before vitrification occurs and fixes the phase separated structure. The ability to directly observe morphological development offers a route toward controlling the length-scale of the final morphology through process control and in situ feedback, from a single stock solution. © 2013 Wiley Periodicals, Inc.