An integrated molecular biology and computational approach to CYP1A1 expression in human brain

The cytochromes P450 comprise a superfamily of heme-containing mono-oxygenases. These enzymes metabolize numerous xenobiotics, but also play a role in metabolism of endogenous compounds. The P450 1A1 enzyme generally metabolizes polycyclic aromatic hydrocarbons, and its expression can be induced by aryl hydrocarbon receptor (AhR) activation. CYP1A1 is an exception to the generality that the majority of CYPs demonstrate highest expression in liver; CYP1Al is present in numerous extrahepatic tissues, including brain. This P450 has been observed in two forms, wildtype (WT) and brain variant (BV), arising from alternatively spliced mRNA transcripts. The CYP1A1 BV mRNA presented an exon deletion and was detected in human brain but not liver tissue of the same individuals. ^ Quantitative PCR analyses were performed to determine CYP1A1 WT and BV transcript expression levels in normal, bipolar disorder or schizophrenic groups. In our samples, we show that CYP1A1 BV mRNA, when present, is found alongside the full-length form. Furthermore, we demonstrate a significant decrease in expression of CYP1A1 in patients with bipolar disorder or schizophrenia. The expression level was not influenced by post-mortem interval, tissue pH, age, tobacco use, or lifetime antipsychotic medication load. ^ There is no indication of increased brain CYP1A1 expression in normal smokers versus non-smokers in these samples. We observed slightly increased CYP1A1 expression only in bipolar and schizophrenic smokers versus non-smokers. This may be indicative of complex interactions between neuronal chemical environments and AhR-mediated CYP1A1 induction in brain. ^ Structural homology modeling demonstrated that P450 1A1 BV has several alterations to positions/orientations of substrate recognition site residues compared to the WT isoform. Automated substrate docking was employed to investigate the potential binding of neurological signaling molecules and neurotropic drugs, as well as to differentiate specificities of the two P450 1A1 isoforms. We consistently observed that the BV isoform produced energetically favorable substrate dockings in orientations not observed for the same substrate in the WT isoform. These results demonstrated that structural differences, namely an expanded substrate access channel and active site, confer greater capacity for unique compound docking positions suggesting a metabolic profile distinct from the wildtype form for these test compounds. ^

Integrated assessment of policy interventions for promoting sustainable irrigation in semi-arid environments: A hydro-economic modeling approach

Sustaining irrigated agriculture to meet food production needs while maintaining aquatic ecosystems is at the heart of many policy debates in various parts of the world, especially in arid and semi-arid areas. Researchers and practitioners are increasingly calling for integrated approaches, and policy-makers are progressively supporting the inclusion of ecological and social aspects in water management programs. This paper contributes to this policy debate by providing an integrated economic-hydrologic modeling framework that captures the socio-economic and environmental effects of various policy initiatives and climate variability. This modeling integration includes a risk-based economic optimization model and a hydrologic water management simulation model that have been specified for the Middle Guadiana basin, a vulnerable drought-prone agro-ecological area with highly regulated river systems in southwest Spain. Namely, two key water policy interventions were investigated: the implementation of minimum environmental flows (supported by the European Water Framework Directive, EU WFD), and a reduction in the legal amount of water delivered for irrigation (planned measure included in the new Guadiana River Basin Management Plan, GRBMP, still under discussion). Results indicate that current patterns of excessive water use for irrigation in the basin may put environmental flow demands at risk, jeopardizing the WFD s goal of restoring the ?good ecological status? of water bodies by 2015. Conflicts between environmental and agricultural water uses will be stressed during prolonged dry episodes, and particularly in summer low-flow periods, when there is an important increase of crop irrigation water requirements. Securing minimum stream flows would entail a substantial reduction in irrigation water use for rice cultivation, which might affect the profitability and economic viability of small rice-growing farms located upstream in the river. The new GRBMP could contribute to balance competing water demands in the basin and to increase economic water productivity, but might not be sufficient to ensure the provision of environmental flows as required by the WFD. A thoroughly revision of the basin s water use concession system for irrigation seems to be needed in order to bring the GRBMP in line with the WFD objectives. Furthermore, the study illustrates that social, economic, institutional, and technological factors, in addition to bio-physical conditions, are important issues to be considered for designing and developing water management strategies. The research initiative presented in this paper demonstrates that hydro-economic models can explicitly integrate all these issues, constituting a valuable tool that could assist policy makers for implementing sustainable irrigation policies.

An integrated modeling approach to assess the impact on road freight transport demand of allowing longer and heavier vehicles (LHVs) in Spain

The assessment on introducing Longer and Heavier Vehicles (LHVs) on the road freight transport demand is performed in this paper by applying an integrated modeling approach composed of a Random Utility-Based Multiregional Input-Output model (RUBMRIO) and a road transport network model. The approach strongly supports the concept that changes in transport costs derived from the LHVs allowance as well as the economic structure of regions have both direct and indirect effects on the road freight transport system. In addition, we estimate the magnitude and extent of demand changes in the road freight transportation system by using the commodity-based structure of the approach to identify the effect on traffic flows and on pollutant emissions over the whole network of Spain by considering a sensitivity analysis of the main parameters which determine the share of Heavy-Goods Vehicles (HGVs) and LHVs. The results show that the introduction of LHVs will strengthen the competitiveness of the road haulage sector by reducing costs, emissions, and the total freight vehicles required.

A hybrid simulation-optimization approach for the design of internally heat-integrated distillation columns

Paper submitted to AIChE 2012 Annual Meeting: Energy Efficiency by Process Intensification, Pittsburgh, PA, October 28-November 2, 2012.

An integrated biopsychosocial approach to understanding awareness deficits in Alzheimer's disease and brain injury

Considerable emphasis has been placed upon cognitive neuropsychological explanations of awareness disorders in brain injury and Alzheimer's disease (AD), with relatively few models acknowledging the role of psychosocial factors. The present paper explores clinical presentations of unawareness in brain injury and AD, reviews the evidence for the influence of psychosocial factors alongside neuropsychological changes, and considers a number of key issues that theoretical models need to address, before going on to discuss some recently-developed models that offer the potential for developing a comprehensive biopsychosocial account. Building on these developments, we present a framework designed to assist clinicians to identify the specific factors contributing to an individual's presentation of unawareness, and illustrate its application with a case example.

An integrated multiple criteria decision making approach for resource allocation in higher education

Resource allocation is one of the major decision problems arising in higher education. Resources must be allocated optimally in such a way that the performance of universities can be improved. This paper applies an integrated multiple criteria decision making approach to the resource allocation problem. In the approach, the Analytic Hierarchy Process (AHP) is first used to determine the priority or relative importance of proposed projects with respect to the goals of the universities. Then, the Goal Programming (GP) model incorporating the constraints of AHP priority, system, and resource is formulated for selecting the best set of projects without exceeding the limited available resources. The projects include 'hardware' (tangible university's infrastructures), and 'software' (intangible effects that can be beneficial to the university, its members, and its students). In this paper, two commercial packages are used: Expert Choice for determining the AHP priority ranking of the projects, and LINDO for solving the GP model. Copyright © 2007 Inderscience Enterprises Ltd.

Strategic logistics outsourcing:an integrated QFD and fuzzy AHP approach

This paper develops an integratedapproach, combining quality function deployment (QFD), fuzzy set theory, and analytic hierarchy process (AHP) approach, to evaluate and select the optimal third-party logistics service providers (3PLs). In the approach, multiple evaluating criteria are derived from the requirements of company stakeholders using a series of house of quality (HOQ). The importance of evaluating criteria is prioritized with respect to the degree of achieving the stakeholder requirements using fuzzyAHP. Based on the ranked criteria, alternative 3PLs are evaluated and compared with each other using fuzzyAHP again to make an optimal selection. The effectiveness of proposed approach is demonstrated by applying it to a Hong Kong based enterprise that supplies hard disk components. The proposed integratedapproach outperforms the existing approaches because the outsourcing strategy and 3PLs selection are derived from the corporate/business strategy.

Risk management in organizations:an integrated case study approach

In any organization, risk plays a huge role in the success or failure of any business endeavour. Measuring and managing risk is a difficult and often complicated task and the global financial crisis of the late noughties can be traced to a worldwide deficiency in risk management regimes. One of the problems in understanding how best to manage risk is a lack of detailed examples of real world practice. In this accessible textbook the author sets the world of risk management in the context of the broader corporate governance agenda, as well as explaining the core elements of a risk management system. Material on the differences between risk management and internal auditing is supplemented by a section on the professionalization of risk – a relatively contemporary evolution. Enterprise risk management is also fully covered. With a detailed array of risk management cases – including Tesco, RBS and the UK government – lecturers will find this a uniquely well researched resource, supplemented by materials that enable the cases to be easily integrated into the classroom. Risk managers will be delighted with the case materials made available for the first time with the publication of this book.

Maximizing Hospitality Learning Outcomes: An Integrated Experiential In-Class Approach

This study explored the influence of an experiential, in-class approach to the hospitality curriculum as a means of increasing its efficiency and effectiveness. Specifically, the study provides an example of how hospitality faculty might utilize an experiential, in-class approach to integrate additional hospitality-specific content along with process and content issues for working in teams and team decision-making. The results of this study support the efficient and effective use of an experiential inclass teaching method. The value of this study is twofold: (1) it provides an initial test of this approach’s usefulness and (2) it provides a forum for continued conversations of how experiential approaches can be utilized to enhance and reinforce other hospitality content and managerial skills and to bridge the gap between vocational and liberal education outcomes.

Linking the ecosystem service approach to social preferences and needs in integrated coastal land use management - a planning approach

Coastal zones with their natural and societal subsystems are exposed to rapid changes and pressures on resources. Scarcity of space and impacts of climate change are prominent drivers of land use and adaptation management today. Necessary modifications to present land use management strategies and schemes influence both the structures of coastal communities and the ecosystems involved. Approaches to identify the impacts and account for (i) the linkages between social references and needs and (ii) ecosystem services in coastal zones have been largely absent. The presented method focuses on improving the inclusion of ecosystem services in planning processes and clarifies the linkages with social impacts. In this study, fourteen stakeholders in decisionmaking on land use planning in the region of Krummhörn (northwestern Germany, southern North Sea coastal region) conducted a regional participative and informal process for local planning capable to adapt to climate driven changes. It is argued that scientific and practical implications of this integrated assessment focus on multifunctional options and contribute to more sustainable practices in future land use planning. The method operationalizes the ecosystem service approach and social impact analysis and demonstrates that social demands and provision of ecosystem services are inherently connected.