Roles of proteolysis in regulation of G protein-coupled receptor function

The enzymatic activity of peptidases must be tightly regulated to prevent uncontrolled hydrolysis of peptide bonds, which could have devastating effects in biological systems. Peptidases are often generated as inactive propeptidases, secreted with endogenous inhibitors or they are compartmentalized. Propeptidases become active after proteolytic removal of N-terminal activation peptides by other peptidases. Some peptidases only become active towards substrates only at certain pHs, thus confining activity to specific compartments or conditions. This review discusses the different roles proteolysis plays in regulating G protein-coupled receptors (GPCRs). At the cell-surface, certain GPCRs are regulated by the hydrolytic inactivation of bioactive peptides by membrane-anchored peptidases, which prevents signaling. Conversely, cell-surface peptidases can also generate bioactive peptides that directly activate GPCRs. Alternatively, cell-surface peptidases activated by GPCRs, can generate bioactive peptides to cause transactivation of receptor tyrosine kinases, thereby promoting signaling. Certain peptidases can signals directly to cells, by cleaving GPCR to initiate intracellular signaling cascades. Intracellular peptidases also regulate GPCRs; lysosomal peptidases destroy GPCRs in lysosomes to permanently terminate signaling and mediate downregulation; endosomal peptidases cleave internalized peptide agonists to regulate GPCR recycling, resensitization and signaling; and soluble intracellular peptidases also participate in GPCR function by regulating the ubiquitination state of GPCRs, thereby altering GPCR signaling and fate. Although the use of peptidase inhibitors has already brought success in the treatment of diseases such as hypertension, the discovery of new regulatory mechanisms involving proteolysis that control GPCRs may provide additional targets to modulate dysregulated GPCR signaling in disease.

A normative method to analyse workarounds in a healthcare environment: motivations, consequences, and constraints

Healthcare information systems have the potential to enhance productivity, lower costs, and reduce medication errors by automating business processes. However, various issues such as system complexity and system abilities in a relation to user requirements as well as rapid changes in business needs have an impact on the use of these systems. In many cases failure of a system to meet business process needs has pushed users to develop alternative work processes (workarounds) to fill this gap. Some research has been undertaken on why users are motivated to perform and create workarounds. However, very little research has assessed the consequences on patient safety. Moreover, the impact of performing these workarounds on the organisation and how to quantify risks and benefits is not well analysed. Generally, there is a lack of rigorous understanding and qualitative and quantitative studies on healthcare IS workarounds and their outcomes. This project applies A Normative Approach for Modelling Workarounds to develop A Model of Motivation, Constraints, and Consequences. It aims to understand the phenomenon in-depth and provide guidelines to organisations on how to deal with workarounds. Finally the method is demonstrated on a case study example and its relative merits discussed.

Control of flowering time in temperate cereals: genes, domestication, and sustainable productivity

The control of flowering is central to reproductive success in plants, and has a major impact on grain yield in crop species. The global importance of temperate cereal crops such as wheat and barley has meant emphasis has long been placed on understanding the genetics of flowering in order to enhance yield. Leads gained from the dissection of the molecular genetics of model species have combined with comparative genetic approaches, recently resulting in the isolation of the first flowering time genes in wheat and barley. This paper reviews the genetics and genes involved in cereal flowering pathways and the current understanding of how two of the principal genes, Vrn and Ppd, have been involved in domestication and adaptation to local environments, and the implications for future breeding programmes are discussed.

Post-occupancy evaluation studies in recently refurbished office building: energy performance and employees' satisfaction

Existing buildings contribute greatly to global energy use and greenhouse gas emissions. In the UK, about 18% of carbon emissions are generated by non-domestic buildings; sustainable building refurbishment can play an important role in reducing carbon emissions. This paper looks at the performance of a recently refurbished 5-storey office building in London, in terms of energy consumption as well as occupants’ satisfaction. Pre- and post-occupancy evaluation studies were conducted using online questionnaire surveys and energy consumption evaluation. Results from pre-occupancy and post-occupancy evaluation studies showed that employees, in general, were more satisfied with their work environment at the refurbished building than with that of their previous office. Employees’ self-reported productivity improved after the move to Elms House. These surveys showed a positive relationship between employees’ satisfaction with their work environment and their self-reported productivity, well-being and enjoyment at work. The factor that contributed to increasing employee satisfaction the most was: better use of interior space. Although the refurbishment was a success in terms of reducing energy consumption per m2, the performance gap was almost 3 times greater than that estimated. Unregulated loads, problems with building control, ineffective use of space and occupants’ behaviour are argued to be reasons for this gap.

Buzz-words in international management education

Buzz words are used by professional academics to signal that the author or speaker is aware of current trends in the subject. Buzz worfds are usually introduced in a specific context, but as they become more popular they are used in other contexts where their meaning is less clear. This creates ambiguity, whhich can be deployed to advance spurious arguments that are difficult for opponents to refute. This thesis is illustrated by reference to the use of the 'strategy' concept in intermnational management education

Multilevel research in the field of organizational behavior: an empirical look at 10 years of theory and research

During the last 30 years, significant debate has taken place regarding multilevel research. However, the extent to which multilevel research is overtly practiced remains to be examined. This article analyzes 10 years of organizational research within a multilevel framework (from 2001 to 2011). The goals of this article are (a) to understand what has been done, during this decade, in the field of organizational multilevel research and (b) to suggest new arenas of research for the next decade. A total of 132 articles were selected for analysis through ISI Web of Knowledge. Through a broad-based literature review, results suggest that there is equilibrium between the amount of empirical and conceptual papers regarding multilevel research, with most studies addressing the cross-level dynamics between teams and individuals. In addition, this study also found that the time still has little presence in organizational multilevel research. Implications, limitations, and future directions are addressed in the end. Organizations are made of interacting layers. That is, between layers (such as divisions, departments, teams, and individuals) there is often some degree of interdependence that leads to bottom-up and top-down influence mechanisms. Teams and organizations are contexts for the development of individual cognitions, attitudes, and behaviors (top-down effects; Kozlowski & Klein, 2000). Conversely, individual cognitions, attitudes, and behaviors can also influence the functioning and outcomes of teams and organizations (bottom-up effects; Arrow, McGrath, & Berdahl, 2000). One example is when the rewards system of one organization may influence employees’ intention to quit and the existence or absence of extra role behaviors. At the same time, many studies have showed the importance of bottom-up emergent processes that yield higher level phenomena (Bashshur, Hernández, & González-Romá, 2011; Katz-Navon & Erez, 2005; Marques-Quinteiro, Curral, Passos, & Lewis, in press). For example, the affectivity of individual employees may influence their team’s interactions and outcomes (Costa, Passos, & Bakker, 2012). Several authors agree that organizations must be understood as multilevel systems, meaning that adopting a multilevel perspective is fundamental to understand real-world phenomena (Kozlowski & Klein, 2000). However, whether this agreement is reflected in practicing multilevel research seems to be less clear. In fact, how much is known about the quantity and quality of multilevel research done in the last decade? The aim of this study is to compare what has been proposed theoretically, concerning the importance of multilevel research, with what has really been empirically studied and published. First, this article outlines a review of the multilevel theory, followed by what has been theoretically “put forward” by researchers. Second, this article presents what has really been “practiced” based on the results of a review of multilevel studies published from 2001 to 2011 in business and management journals. Finally, some barriers and challenges to true multilevel research are suggested. This study contributes to multilevel research as it describes the last 10 years of research. It quantitatively depicts the type of articles being written, and where we can find the majority of the publications on empirical and conceptual work related to multilevel thinking.

Evaluating business value of IT towards optimisation of the application portfolio

Information technology has become heavily embedded in business operations. As business needs change over time, IT applications are expected to continue providing required support. Whether the existing IT applications are still fit for the business purpose they were intended or new IT applications should be introduced, is a strategic decision for business, IT and business-aligned IT. In this paper, we present a method which aims to analyse business functions and IT roles, and to evaluate business-aligned IT from both social and technical perspectives. The method introduces a set of techniques that systematically supports the evaluation of the existing IT applications in relation to their technical capabilities for maximising business value. Furthermore, we discuss the evaluation process and results which are illustrated and validated through a real-life case study of a UK borough council, and followed by discussion on implications for researchers and practitioners.

The agile governance of business IT projects

Organisations typically define and execute their selected strategy by developing and managing a portfolio of projects. The governance of this portfolio has proved to be a major challenge, particularly for large organisations. Executives and managers face even greater pressures when the nature of the strategic landscape is uncertain. This paper explores approaches for dealing with different levels of certainty in business IT projects and provides a contingent governance framework. Historically business IT projects have relied on a structured sequential approach, also referred to as a waterfall method. There is a distinction between the development stages of a solution and the management stages of a project that delivers the solution although these are often integrated in a business IT systems project. Prior research has demonstrated that the level of certainty varies between development projects. There can be uncertainty on what needs to be developed and also on how this solution should be developed. The move to agile development and management reflects a greater level of uncertainty often on both dimensions and this has led the adoption of more iterative approaches. What has been less well researched is the impact of uncertainty on the governance of the change portfolio and the corresponding implications for business executives. This paper poses this research question and proposes a govemance framework to address these aspects. The governance framework has been reviewed in the context of a major anonymous organisation, FinOrg. Findings are reported in this paper with a focus on the need to apply different approaches. In particular, the governance of uncertain business change is contrasted with the management approach for defined IT projects. Practical outputs from the paper include a consideration of some innovative approaches that can be used by executives. It also investigates the role of the business change portfolio group in evaluating and executing the appropriate level of governance. These results lead to recommendations for executives and also proposed further research.

A gestalt generated from grounded theory concerning intuition in IS research

Intuition is an important and under-researched concept in information systems. Prior exploratory research has shown that that there is potential to characterize the use of intuition in academic information systems research. This paper extends this research to all of the available issues of two leading IS journals with the aim of reaching an approximation of theoretical saturation. Specifically, the entire text of MISQ and ISR was reviewed for the years 1990 through 2009 using searchable PDF versions of these publications. All references to intuition were coded on a basis consistent with Grounded Theory, interpreted as a gestalt and represented as a mind-map. In the period 1990-2009, 681 incidents of the use of "intuition", and related terms were found in the articles reviewed, representing a greater range of codes than prior research. In addition, codes were assigned to all issues of MIS Quarterly from commencement of publication to the end of the 2012 publication year to support the conjecture that coding saturation has been approximated. The most prominent use of the term of "intuition" was coded as "Intuition as Authority" in which intuition was used to validate a statement, research objective or a finding; representing approximately 34 per cent of codes assigned. In research articles where mathematical analysis was presented, researchers not infrequently commented on the degree to which a mathematical formulation was "intuitive"; this was the second most common coding representing approximately 16 per cent of the codes. The possibly most impactful use of the term "intuition" was "Intuition as Outcome", representing approximately 7 per cent of all coding, which characterized research results as adding to the intuitive understanding of a research topic or phenomena.This research aims to contribute to a greater theoretical understanding of the use of intuition in academic IS research publications. It provides potential benefits to practitioners by providing insight into the use of intuition in IS management, for example, emphasizing the emerging importance of "intuitive technology". Research directions include the creation of reflective and/or formative constructs for intuition in information systems research and the expansion of this novel research method to additional IS academic publications and topics.

Engineering the electronic bandgaps and band edge positions in carbon-substituted 2D boron nitride: a first-principles investigation

Modification of graphene to open a robust gap in its electronic spectrum is essential for its use in field effect transistors and photochemistry applications. Inspired by recent experimental success in the preparation of homogeneous alloys of graphene and boron nitride (BN), we consider here engineering the electronic structure and bandgap of C2xB1−xN1−x alloys via both compositional and configurational modification. We start from the BN end-member, which already has a large bandgap, and then show that (a) the bandgap can in principle be reduced to about 2 eV with moderate substitution of C (x < 0.25); and (b) the electronic structure of C2xB1−xN1−x can be further tuned not only with composition x, but also with the configuration adopted by C substituents in the BN matrix. Our analysis, based on accurate screened hybrid functional calculations, provides a clear understanding of the correlation found between the bandgap and the level of aggregation of C atoms: the bandgap decreases most when the C atoms are maximally isolated, and increases with aggregation of C atoms due to the formation of bonding and anti-bonding bands associated with hybridization of occupied and empty defect states. We determine the location of valence and conduction band edges relative to vacuum and discuss the implications on the potential use of 2D C2xB1−xN1−x alloys in photocatalytic applications. Finally, we assess the thermodynamic limitations on the formation of these alloys using a cluster expansion model derived from first-principles.

The role of industry bodies in changing market practices through self-regulation: commercial property leasing in the UK

The UK government has sought to make changes to commercial property leasing practices. This has been the case since the recession of the 1990s. Industry self-regulation using an industry code of practice has been the vehicle for these changes. However, the code has had little direct success in changing practices. This is despite repeated threats of legislation as a constant backdrop to this initiative. The focus for this research is on the role of the industry bodies in the code initiative. They have been central to self-regulation in commercial leasing. Thus, the aim is to investigate the role of industry bodies in the process of institutional change. The context is industry self-regulation. The specific setting is commercial leasing. The main industry bodies in focus are the British Property Federation and Royal Institution of Chartered Surveyors. An existing model of institutional change forms the framework for the research. A chronological narrative is constructed from secondary data. This is analysed, identifying the actions of the industry bodies within the conceptual stages of the model. The analysis shows that the industry bodies had not acted as convincing agents of change for commercial leasing. In particular there was a lack of theorisation, a key stage in the process. The industry bodies did not develop a framework necessary to guide their members through the change process. These shortcomings of the industry bodies are likely to have contributed to the failure of the Code. However, the main conclusion is that, if industry self-regulation is led by government, then the state must work with industry bodies to harness their potential as champions and drivers of institutional change. This is particularly important in achieving change in institutionalised environments.

Intraspecific trait variation is correlated with establishment success of alien mammals

Many studies have aimed to identify common predictors of successful introductions of alien species, but the search has had limited success, particularly for animals. Past research focused primarily on mean trait values, even though genetic and phenotypic variation has been shown to play a role in establishment success in plants and some animals (mostly invertebrates). Using a global database describing 511 introduction events representing 97 mammalian species, we show that intraspecific variation in morphological traits is associated with establishment success, even when controlling for the positive effect of propagule pressure. In particular, greater establishment success is associated with more variation in adult body size but, surprisingly, less variation in neonate body size, potentially reflecting distinct trade-offs and constraints that influence population dynamics differently. We find no mean trait descriptors associated with establishment success, although species occupying wider native distribution ranges (which likely have larger niches) are more successful. Our results emphasize the importance of explicitly considering intraspecific variation to predict establishment success in animal species and generally to understand population dynamics. This understanding might improve management of alien species and increase the success of intentional releases, for example, for biocontrol or reintroductions.