Challenges in mass spectrometry-based quantification of bioactive peptides: A case study exploring the neuropeptide Y family

The study of biologically active peptides is critical to the understanding of physiological pathways, especially those involved in the development of disease. Historically, the measurement of biologically active endogenous peptides has been undertaken by radioimmunoassay, a highly sensitive and robust technique that permits the detection of physiological concentrations in different biofluid and tissue extracts. Over recent years, a range of mass spectrometric approaches have been applied to peptide quantification with limited degrees of success. Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) belong to the NPY family exhibiting regulatory effects on appetite and feeding behavior. The physiological significance of these peptides depends on their molecular forms and in vivo concentrations systemically and at local sites within tissues. In this report, we describe an approach for quantification of individual peptides within mixtures using high-performance liquid chromatography electrospray ionization tandem mass spectrometry analysis of the NPY family peptides. Aspects of quantification including sample preparation, the use of matrix-matched calibration curves, and internal standards will be discussed. This method for the simultaneous determination of NPY, PYY, and PP was accurate and reproducible but lacks the sensitivity required for measurement of their endogenous concentration in plasma. The advantages of mass spectrometric quantification will be discussed alongside the current obstacles and challenges. © 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 357–366, 2012.

Tampere region under the microscope : a critical analysis from the knowledge perspective

Purpose – In the context of global knowledge economy, knowledge-based urban development (KBUD) is seen as an effective development strategy for city-regions to survive, flourish and become highly competitive urban agglomerations – i.e., a knowledge city-region. This paper aims to evaluate the KBUD dynamics, capacity and potentials of a rapidly emerging knowledge city-region of Finland – Tampere region. Design/methodology/approach – The paper undertakes a review of the literature on regional development in the knowledge economy era. It adopts a qualitative analysis technique to scrutinize the dynamics, capacity and potentials of Tampere region. The semi-structured interview process starts with the pre-determined key actors of the city-region with an aim of determining the other key players. Next, with the participation of all key players to the interviews, the research reveals the principal issues, assets and mechanisms that relate to KBUD, and portrays the strengths, weaknesses, opportunities and threats of the city-region. A critical analysis of the findings along with the previous studies is undertaken to provide a clear picture of the dynamics, capacity and potentials of the emerging knowledge city-region. Originality/value – This paper reports the findings of a pioneering study focusing on the investigation of the KBUD dynamics, capacity and potentials of Tampere region. The paper critically evaluates the city-region from the knowledge perspective with the lens of KBUD, and the lessons learned and the methodological approach of the paper shed light to other city-regions seeking such development. Practical implications – The paper discusses the findings of a study from Tampere region that critically scrutinizes the KBUD experience of the city-region. The research provides an invaluable opportunity to inform the regional decision-, policy- and plan-making mechanisms by determining key issues, actors, assets, processes and potential development directions for the KBUD of Tampere region.

Critical applied linguistics

This chapter provides a historical materialist review of the development of applied and critical linguistics and their extensions and applications to the fields of English Language studies. Following Bourdieu, we view intellectual fields and their affiliated discourses as constructed in relation to specific economic and political formations and sociocultural contexts. We therefore take ‘applied linguistics’, ‘critical language studies’ and ‘English language studies’ as fields in dynamic and contested formation and relationship. Our review focuses on three historical moments. In the postwar period, we describe the technologisation of linguistics – with the enlistment of linguistics in the applied fields of language planning, literacy education and second/foreign language teaching. We then turn to document the multinationalisation of English, which, we argue entails a rationalisation of English as a universal form of economic capital in globalised economic and cultural flows. We conclude by exploring scenarios for the displacement of English language studies as a major field by other emergent economic lingua franca (e.g., Mandarin, Spanish) and shifts in the economic and cultural nexus of control over English from an Anglo/American centre to East and West Asia.

Teaching and assessing critical thinking : the interaction of student approaches to learning and teaching approaches

This study explored the relationship among student approaches to learning and teaching methods on critical thinking in two business units. Key findings included differences in critical thinking scores between student approaches to learning and some evidence of an interaction between student approaches to learning and critical thinking teach method (immersion vs. infusion). Possible explanations for the results are examined and implications for developing critical thinking skills across a degree discussed. What is apparent is that as Universities move towards program-wide level assessment of critical thinking, further work is required in terms of the design of critical thinking teaching interventions and assessment at the unit, school, and degree level. The session will discuss the challenges in developing critical thinking programs in individual units and at the Faculty level.

Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer

Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.

School-community engagement : a critical approach to involving young people in an urban planning project

This study examines the participation of a group of high school students in designing a Heritage Journey as part of an urban redevelopment project in their community. School-community engagement offers young people an opportunity to engage in community life and influence decisions that affect them. Forging links between community and school is becoming more important for teachers as they attempt to create new authentic learning opportunities for young people within a changing world. Increasingly, researchers and urban planners are including children and young people as active decision makers and participants in community engagement projects. However, models of participation tend to be adult-focussed, conceive participation in terms of low to high graduated levels and lack a clearly articulated theoretical basis. The research problem in this study focuses on investigating whether the inclusion of young people in school-community engagement results in value adding to urban planning and is an example of genuine participation. The aim of the study is to provide a theoretically informed, empirically rich understanding of the inclusion of young people in a community engagement strategy for an urban planning project. Theories of space developed by Henri Lefebvre and Edward Soja are drawn upon for understanding how space is understood, used, and redeveloped by the students and other stakeholders. The study also draws on David Harvey’s notion of utopia and space to consider the imaginative possibilities of the students’ designs and ideas. The study uses a participatory research approach and documents the opportunities and challenges of this methodology. The thesis argues that school-community engagement within a "Thirdspace" offers many new opportunities for the emergence of authentic learning situations. Key findings from the study show young people’s participation in an urban planning project can achieve successful results when young people are given opportunities for full participation in decision-making processes; multiple pathways for active engagement are incorporated into the research design; opportunities for mentoring are provided; realistic timelines are communicated to all stakeholders and the needs and social practices of the local community are acknowledged. A new spatial model of community engagement is proposed as an outcome of the study. Unlike previous models of participation, this model demonstrates how exclusion and inclusion can be conceived visually, and may prove effective for conceptualising future community engagement projects that involve young people.

Ownership structure and concentration and the timeliness of corporate earnings : Malaysian evidence

This thesis provides the first evidence on how ownership concentration and structure relate to the timeliness of price discovery and reporting lags in Malaysia. Based on a sample of 1,276 Malaysian firms from 1996 to 2009, the results show that ownership concentration and the identity of the largest shareholder matter to the timeliness of price discovery and reporting lags. Specifically, closely-held firms are more timely in their price discovery and have shorter reporting lags, particularly if the largest shareholder is a foreigner or a financial institution. Government-owned firms have longer reporting lags, as expected, but we find no evidence that family-owned firms have significantly different timeliness of price discovery and reporting lags than other firms. Additional analysis shows that prior to the implementation of the Malaysian Code of Corporate Governance, firms were more timely in their price discovery but longer in their reporting lag.

Contractual relationships for better stewardship of privatised critical infrastructures

Governments increasingly rely on forms of privatisation to provide critical public infrastructure yet when those infrastructures fail to meet community expectations government bears the political and economic risks, being held accountable by the public as steward for those infrastructures. Reconfiguration of the contractual relationships may achieve better stewardship. Many of the forms of privatization rely on Agency theory prescriptions, conceptualizing organisations and individuals as motivated solely by self-interest. Stewardship theory (Van Slyke 2007) has developed as a complement to Agency theory offering the possibility of contractual relationships which maximize stewardship outcome. Stewardship theory asserts that pro-stewardship factors cause the agent/steward to act in the interests of the principal. This research has interrogated the literature finding that of the pro-stewardship factors, sense of responsibility is pre-eminent and has a significant link to the agent acting as a steward. The research has explored how important it is that the steward feel sense of responsibility and the actions that sense of responsibility. Case studies of privatized core elements of urban water systems infrastructure were explored. Data has been gathered primarily from archival sources and individual interviews of government and private sector executives key to those systems. This paper reports the findings as to the extent of stewardship, how important it is that the steward acts in the interests of the principal, even to the steward’s detriment and the importance of the steward feeling a sense of responsibility. The actions which increase that sense of responsibility will be assembled to position the research to better proceed with the analysis of the data as to these actions.