bluuebunny/crossref_metadata_2025 huggingface dataset:
Disaster preparedness measures: a test case development and application
Authors: Simpson David M.
Published: November 2008

Purpose

This paper sets out to develop disaster preparedness measurement methodology using a small test case of two communities. It is aimed at furthering discussion of the issues and complexities of developing measurement of preparedness indicators for application and utilization.

Design/methodology/approach

The study used a multi‐modal approach, utilizing several data sources, including: a survey of essential facility managers in the two communities; document data extracted from the two city's Comprehensive Plans, Budgets, and the Emergency Operation Plans; and key informant interviews. Data collected from these sources formed the basis of the model construction and testing.

Findings

The primary conclusion is that a preparedness measurement model, while inherently difficult to construct and execute, has the potential to assist in the comparison and evaluation of community preparedness. Further such development requires additional refinement, calibration, and applied testing.

Research limitations/implications

In terms of future research, this type of effort is preliminary, and needs to be tested across a larger number of communities to gauge its accuracy, and would most benefit from the creation of consistent baseline scores for a larger cross‐section of communities. Baseline scores could be examined for disasters that affect multiple communities, and comparison and evaluations of the preparedness measures can be applied. Future research should calibrate the model using expert and community feedback.

Practical implications

Should a standardized measurement and indicator system be developed with wide application, there would be effects in the insurance, regulatory and management sectors.

Originality/value

The paper creates a measurement and indexing process for discussion and evaluation in the hazards research community.
Disaster preparedness for sustainable development in Bangladesh
Authors: Shah Alam Khan M.
Published: November 2008

Purpose

Bangladesh is one of the most disaster‐prone countries in the world. Natural disasters adversely affect the country's economy and deter its development. Thus preparedness for the disasters, along with effective prevention and mitigation measures, is imperative for sustainable development of the country. The purpose of this paper is to examine the present state of disaster preparedness in the country with special attention to the more frequent and damaging disasters – flood and cyclone.

Design/methodology/approach

A detailed study of the effects of natural disasters, disaster prevention and mitigation measures, and institutional setting for disaster preparedness was undertaken.

Findings

Plans and programs have been formulated to manage natural disasters. In a “Cyclone Preparedness Program”, trained volunteers facilitate emergency response and proper use of the multi‐purpose shelters. Within an institutional framework for disaster management, several Non‐Government Organizations (NGOs) work for disaster preparedness alongside the government organizations. Their formal and nonformal education programs on disaster preparedness have a common objective of promoting resilient and sustainable communities.

Practical implications

Planning and design of structural interventions for prevention and mitigation of natural disasters should be done more carefully to avoid adverse impacts on the environment. A participatory approach is essential in this process. Education and awareness‐building programs need wider and easier access to the people.

Originality/value

The paper concludes that the institutional arrangement for cyclone preparedness and response is unique and efficient, and that participation of NGOs in the preparedness program contributes significantly toward sustainable development. These lessons will be important for development planning in other sectors.
Mass fatality management after the Indian Ocean tsunami
Authors: Phillips Brenda , Neal Dave , Wikle Thomas , Subanthore Aswin , Hyrapiet Shireen
Published: November 2008

Purpose

This study aims to conduct the first original research on mass fatality management in nearly 30 years.

Design/methodology/approach

A qualitative research design captured local perspectives within a culturally‐appropriate context to examine roles and responsibilities of government officials within the State of Tamil Nadu and District of Naggapattinam (spellings reflect the most commonly‐used local choice), India. Research data were gathered in the context of the Indian Ocean Tsunami that claimed nearly 300,000 lives across approximately 13 nations.

Findings

Local officials and residents faced unprecedented challenges during the hours immediately following the tsunami. These included removing debris that covered bodies, body identification, health and sanitation issues, and the necessity of creating mass graves. The findings identify prior experience with disasters, familiarity with the local area, the quality of pre‐existing networks among officials, a strong desire to rescue those yet living and the presence of linkages between government and non‐governmental organizations as critical factors affecting an expedited management process.

Practical implications

Practical implications include the value of general disaster training that can transcend specific circumstances, the pre‐establishment of mutual aid agreements, strong lines of horizontal and vertical cooperation and inter‐organizational coordination and an understanding of local culture and customs.

Originality/value

The paper contributes to scant social science understanding of mass fatality management processes and furthers a line of inquiry applicable to a wide variety of hazards such as pandemics, terrorism and natural events.
US corporate public relations in the progressive era
Authors: Gower Karla
Published: November 2008

Purpose

This paper aims to explore the concept of public relations in the progressive era to gain a greater understanding of the historical development of corporate public relations in the USA.

Design/methodology/approach

The paper provides historical analysis of 87 magazine articles dating from 1900 to 1917, which discussed press agentry, publicity, and public relations.

Findings

In the early 1900s, publicity meant both legal requirements of corporate disclosure and press exposure of secret corporate activities. The purpose of publicity was to reveal excess and corruption. The term press agent was used in two ways. First, it was used to refer to literary and theatrical press agents, and second, it was used interchangeably with publicity agent to signify individuals hired by corporations to respond to the publicity and explain corporate policies to the public. By the second decade of the twentieth century, corporations, specifically the railroads, were using the term public relations to refer to the practice of developing relationships with the public.

Originality/value

Most historical studies of public relations in the USA have described the development of the field as a linear progression or evolution from press agentry, to public information or publicity, to two‐way communication. This study suggests that that linear evolutionary model is only partially accurate. At least some corporations in the progressive era had a greater understanding of the two‐way street than corporations in this period normally are given credit for.
Writing PR history: issues, methods and politics
Authors: L'Etang Jacquie
Published: November 2008

Purpose

The purpose of this paper is to argue that public relations (PR) history‐writing has profoundly shaped the discipline and that its US bias may have limited theoretical developments. The author aims to explore the challenges in writing PR history and to consider some of the strategic philosophical issues and challenges that face historians.

Design/methodology/approach

Historical interpretations are shaped by authors' social constructions and thus the paper is written reflexively. The author discusses the way in which histories are structured and patterned by their authors' assumptions and values about the nature of time; human civilisation, progressivism, situationalism, inevitability, human agency, cultural change, flux and transformation.

Findings

Existing (largely US) PR historical writing is analysed in terms of its theoretical impact through the “four models” and it is argued that this typology is not appropriately applied to other cultures with different paths of historical evolution. As a way of demonstrating this point, key aspects of British developments in the twentieth century are drawn out to reveal a dozen “models” of PR practice that could potentially form the basis of theoretical research.

Originality/value

Overall, the paper contributes a discussion of historical methodology in relation to PR; shows the connection between history and theory‐building in PR; and demonstrates that history from other cultures can reveal alternative models for theoretical development.
Howard Chase: the man who invented issue management
Authors: Jaques Tony
Published: November 2008

Purpose

The purpose of this paper is to assess the work of Howard Chase within the history of public relations, his role in the birth and development of issue management, and his relevance for contemporary practice.

Design/methodology/approach

Research for this paper draws heavily on the speeches and writings of Chase himself, both before and after the formal establishment of issue management, as well as commentary from key writers.

Findings

While Chase is widely acknowledged as the founder of issue management in 1976, his writings reveal that he saw this “new science” as only one part of a much broader restructuring of management design in which he positioned public policy and profit as corporate objectives of equal importance. Analysis confirms his work was innovative and of historical significance, but it has been increasingly outdated by evolution of the discipline he created.

Originality/value

Despite Chase's pioneering role, modern writing in the field usually cites little more than his definitions and his process model. This paper revisits his original concepts in their contemporary context, providing a fresh framework against which to properly assess his contribution.
Fred Harvey Company public relations and publicity (1876‐1933)
Authors: Curtin Patricia A.
Published: November 2008

Purpose

This paper aims to examine the entrepreneurial Fred Harvey Company's early public relations and publicity efforts to determine what they add to our knowledge of the development of public relations in the USA.

Design/methodology/approach

This historical analysis uses mainly data gleaned from an in‐depth examination of the two archival sources available: the Fred Harvey Company photographs and papers at the Heard Museum in Phoenix, AZ (at about ten linear feet, the most complete collection of Harvey materials), and the Fred Harvey Collection at the University of Arizona (photographs, correspondence, and miscellaneous records).

Findings

Although the dominant historical perspective has labeled this era the “Seedbed Years” and characterized them as “a day of business arrogance toward employee and citizen alike”, this case suggests that other models of practice were in use that developed out of differing cultural milieux. To the dominant view of public relations developing in the USA as a result of business pressures, then, should be added the perspective of organizational culture and the role it played in the development and professionalism of the field.

Research limitations/implications

This one case study cannot be generalized to the whole field; however, the findings support those of a growing number of other scholars (Sullivan, Piasecki), suggesting that the dominant evolutionary paradigm of US public relations history artificially constricts our understanding of the field.

Practical implications

The insider's perspective gained through this study has implications for professionalism, integrated communications, and ethical practice.

Originality/value

This paper examines a previously unknown case in US public relations history and sheds light on early public relations and publicity methods that challenge the dominant paradigm in US scholarship. The notion of press agentry as the dominant practice is explored and challenged.
An assessment of the potential returns of energy certificates for the UK household sector
Authors: McGilligan C. , de Wilde P. , Goodhew S.
Published: November 2008

Purpose

This article seeks to investigate the interconnections between the expectations of the impact of energy certificates issued within the UK domestic building sector through the Energy Performance of Buildings Directive (EPBD) and the actual number and financial implications of the energy saving measures (ESMs) achieved.

Design/methodology/approach

The methodology uses two previously published surveys and compares these with a third independent survey by the authors focusing upon the discrepancies between planned action and implemented action, introducing the term human factor element (hfe).

Findings

The article concludes that annual carbon savings arising from implementation of the Energy Performance Certificate (EPC) may be as low as 73.4 ktC over the five year term of the Kyoto Protocol even though 44 per cent of energy saving measure costs of £200 million are recouped within the same time period and savings will continue for up to 40 years. Achieving annual savings of only 14.7 ktC by 2010, such a figure represents a mere 0.3 per cent of the annual domestic 4.8 MtC savings announced by the government in its 2006 Climate Change Programme.

Practical implications

Since the principal determinant in the uptake of ESMs is initial cost, it is considered that the EPBD is likely to remain an under‐performing instrument in the promotion of energy sufficiency until such time as other complementary provisions are introduced.

Originality/value

Sheds light upon the likely financial impact upon energy efficiency in domestic buildings by energy certificates.
An appraisal of the factors affecting production of cost estimate for electrical services in Nigeria
Authors: Babalola Olubola , Abiodun Adesanya David
Published: November 2008

Purpose

Electrical services contribute a substantial percentage of total construction cost of any particular project. It is essential for estimators to have a detailed knowledge of the factors that affect the incorporation of electrical services cost into the overall building project cost. The overall aim of the study that formed the basis for this paper therefore was to investigate the factors that influence cost estimating of electrical services project.

Design/methodology/approach

The study was carried out based on questionnaire survey of 225 organizations that are involved in cost estimating of electrical services projects in Nigeria. A total of 158 questionnaires out of the 163 retrieved were appropriate for analysis. A list of factors potentially influencing cost estimate for electrical services was identified for the respondents to rate. The data collected were analyzed using factor analysis based on principal component analysis and varimax orthogonal rotation.

Findings

The results shows that the factors affecting production of cost estimate for electrical services could be grouped into four principal factors: the most important factor grouping being estimator competence followed by project technicality, economic requirements and contract requirements.

Practical implications

Many factors are considered by practitioners in the preparation of cost estimate for electrical work in construction project development. The paper has listed about 23 factors that are relevant. However, this paper has shown that four principal factors need to be considered as they explain 64 percent of the factors affect cost estimate production for building project's electrical service works.

Originality/value

Review of literature has shown that there is limited empirical research on the factors influencing cost estimate production for electrical services work. The paper has produced an empirical research on the crucial factors that must be taken into account when producing cost estimate for the electrical service projects.
Why did management and auditors fail to identify ineffective internal controls in their initial SOX 404 reviews?
Authors: Chan Kam C. , Lee Picheng , Seow Gim S.
Published: November 2008

Purpose

The purpose of this paper is to investigate the rationale for the failure of management and auditors to identify material internal control weaknesses (ICWs) in their initial Sarbanes‐Oxley Act of 2002 (SOX) 404 reviews, resulting in subsequent restatement of their opinions.

Design/methodology/approach

The paper focuses on the factors associated with the failure of management and auditor to identify material internal controls weaknesses in their initial SOX 404 reports. Logistic regression is run on a sample of 56 firms that reported material internal controls weaknesses in their amended internal control reports and a control group of 344 firms that reported material internal controls weaknesses (i.e. ineffective internal controls) in their initial internal control reports for 2004.

Findings

The results show that firm size, the use of a Big 4 auditor, the ratio of non‐audit to total fees, and the need for accounting restatements are positively associated with the probability to file an amended internal control report. The number of ICWs and the number of audit committee meetings are negatively associated with the probability to file an amended internal control report.

Practical implications

The paper's findings suggest that regulators and corporate boards should consider providing more guidelines on audit committee practices in addition to the audit committee structure. For example, more guidance by the board is needed to ensure that the audit committee is active in overseeing the company's auditor–client relationship and its internal audit function.

Originality/value

Empirical findings on factors associated with the failure of management and auditor to identify material ICWs in their SOX 404 review can contribute to an understanding of factors affecting the efficiency of the SOX 404 review by attributing such failure to either inherent factors such as operational complexity and industry membership or to managerial choices in auditor‐client relationship and corporate governance issues. An understanding of these factors can help companies and the Public Company Accounting Oversight Board and the Securities and Exchange Commission in their efforts to improve the effectiveness and the efficiency of the current SOX 404 process.
Antecedents and consequences of financial analyst turnover
Authors: Mohammad Emad , Nathan Siva
Published: November 2008

Purpose

The purpose of this paper is to examine the factors leading to turnover among sell‐side financial analysts and the consequences of turnover.

Design/methodology/approach

The paper identifies two types of turnover, voluntary and involuntary, and defines voluntary (involuntary) as when analysts leave their employment at one brokerage firm and find (do not find) employment at another brokerage firm. Logistic models are estimated relating the probability of turnover to factors that explain turnover for both voluntary and involuntary turnover.

Findings

The paper finds that job performance is positively (negatively) related to voluntary (involuntary) turnover. This finding is consistent with Jackofsky's theory predicting U‐shaped relationship between performance and turnover. For voluntary turnover, analysts' performance and job conditions at the new brokerage firm are examined and related to the factors leading to turnover. It was found that turnover analysts move to smaller brokerage firms and become more accurate. They have lighter workload and enjoy more prestige at the new brokerage firm as they follow larger firms and fewer firms and industries.

Originality/value

This is the first study to apply Jackofsky's theory to the financial analysts' profession. Also, it is the first study to document the consequences to voluntary analyst turnover.
Regional economies and potentials of Northeast China
Authors: Yau Laurence Yuen Chin
Published: November 2008

Purpose

The purpose of this paper is to focus on the regional development of Northeast China and recommend certain alternatives to revive its economies.

Design/methodology/approach

The paper reviews and analyses the transitional situations of the major three constituent provinces of Northeast China, namely Liaoning, Jilin and Heilongjiang during the economic reform.

Findings

The paper finds that, in the initial couple of decades since the foundation of The People's Republic of China, a significant part of the northeast economy mirrored the economic model of the USSR, which ineffectively reacted to market economy. The transitional economy reformed the weaknesses of the economic systems of Northeast China but led to regional economic issues in unemployment, productivity, non‐recurrent resources, and duplicated investments.

Practical implications

With the state's northeast revitalization policy and the reform measures of provincial governments, the economic situation of the region has progressively improved over the years, reflected in a higher increase rate in added value of industrial output, international trade and investments. However, the northeast still has shortfalls compared with other economic poles in China.

Originality/value

The paper concludes that the Northeast should strengthen its regional comparative advantages and adopt industrial cluster development for its revival; and it is presumed that regional international trade and foreign direct investments will be further advanced through the more open policies implemented in recent years.
Trade and competition policies at the crossroads: conflicts and synergies on the long run
Authors: Mihaela Dima Alina , Muşetescu Radu , Păun Cristian
Published: November 2008

Purpose

The purpose of the paper is to prove that the abandonment of the issues of competition in the multilateral framework is not an ultimate verdict that strictly separates the two public policies: trade and competition policy.

Design/methodology/approach

The paper critically examines the conflicts between the two policies (competition and trade), through an insight analysis and case interpretation, evaluates different opinions and makes some suggestions to support the logical conclusion that these two fields cannot be separated.

Findings

The final consideration is the synergy between the two is an imperative; or in other words, any specific policy dealing with only one of the fields will be successful in the long term only by taking into consideration the effects in the other field.

Practical implications

The World Trade Organization had to make a choice not between the half full or the half empty glass but between a full glass – difficult to manage because of the danger to spill over – and a half‐full glass – easy to manage because of the large margin.

Originality/value

The paper critically examines the conflicts between the two policies (competition and trade), through an insight analysis and case interpretation.
Sensing or knowing?
Authors: Veale Roberta
Published: November 2008

Purpose

The study seeks to quantify the ability of consumer knowledge (both objective and subjective) and personal self‐confidence to moderate consumer reliance on price and country of origin (COO) when evaluating wine quality, when all intrinsic cues are experienced through sensory perceptions.

Design/methodology/approach

Taste testing experiments were conducted (N = 263) using unwooded chardonnay wine as stimulus, in a three (COO) × three (price) by three (acid level) conjoint analysis fractional factorial design. Specific measures were employed to quantify consumer objective knowledge, subjective knowledge and personal self‐confidence as clearly delineated constructs, in order to investigate the ability of each to moderate extrinsic cue usage.

Findings

Analysis revealed price and COO were both stronger contributors to perceptions of wine quality than taste, irrespective of knowledge (objective or subjective) or self‐confidence levels. Reliance was found to remain extremely consistent although objective product quality was manipulated to three differing levels in a controlled laboratory environment. The research clearly demonstrates that consumer belief in the price/value schema dominates quality assessment for consumers, with COO also found to be a strong influence. This is in spite of varying knowledge and self‐confidence levels.

Practical implications

Results show that marketers cannot assume that intrinsic product attributes, even when experienced, will be weighted and interpreted accurately by consumers – even those considered “knowledgeable”.

Originality/value

The research significantly advances our understanding of consumer knowledge (type and level) and their use of extrinsic cues (price and COO specifically), in relation to their respective influence in their determination of both expected and experienced quality.
The gap between wine expert ratings and consumer preferences
Authors: Schiefer Jan , Fischer Christian
Published: November 2008

Purpose

Expert wine awards are commonly used by consumers to reduce complexity in wine choice but little is known about expert vs non‐expert perceptions of sensory wine quality. This paper aims to examine if expert ratings are suitable quality indicators for consumers and whether there are certain groups of consumers that find expert awards more useful than others.

Design/methodology/approach

The paper compares German consumer ratings obtained in a sensory laboratory with German Agricultural Society's quality competition awards. it tests for the correspondence between expert and non‐expert ratings and for the concordance within the non‐expert group. Estimation of a linear mixed model serves to identify consumer‐side variables with an influence on individual rating distance.

Findings

Correspondence between expert and non‐experts and concordance within the non‐expert group were found to be insignificant. Experienced wine consumers with sufficient specific knowledge and superior self‐reported sensory skills better replicated expert ratings.

Research limitations/implications

With 216 wine ratings obtained from 36 German consumers, the number of observations is small. Future research should verify above findings by considering more consumers and the stability of ratings across time.

Practical implications

The findings suggest that although some consumer segments may find expert awards to be useful decision cues, for a large portion of the market, there is demand for a more consumer‐orientated system of sensory quality evaluation and labelling.

Originality/value

This paper is the first to address the usefulness of expert ratings to novice and experienced wine consumer populations. The statistical procedures employed (including linear mixed modelling) are shown to be useful techniques to handle the repeated measurement nature of the data.
Corporate governance in Europe: raising the bar
Authors: Albert‐Roulhac Catherine
Published: November 2008

Purpose

The purpose of this paper is to provide a comprehensive overview of European Boards. Analyzes Board composition, working style, remuneration and disclosure levels. Looks to the past and to the future as countries are placed in their local context while comparing their progress with each other.

Design/methodology/approach

The article is based on the research by Heidrick & Struggles for its biennial report on Corporate Governance in Europe. The article is based on the analysis of the annual report and official publications of the top companies by market capitalization from national indexes in 10 countries. Each of the 294 companies was rated individually to a maximum rating of 16, to produce a country average, from which we generate a European average. Rating criteria include the working style of the Board, its composition and disclosure levels. The full Report can be found on the Heidrick & Struggles' website: www.heidrick.com Findings – Empirical research highlights significant progress on corporate governance in all countries and increasing convergence both within countries and across Europe. Compliance has become a fact of life now for the Boards of most organizations. Emphasis has shifted towards performance. Nonetheless much remains to be done as corporate governance pressures remain at the forefront of Board agenda.

Originality/value

The paper is based on original empirical research. The objectivity and consistent methodology ensures that the paper is a useful reference for anyone tracking corporate governance practices in Europe.
Corporate social responsibility practices in the pharmaceutical industry
Authors: Smith Alan D.
Published: November 2008

Purpose – The purpose of this paper is to provide practitioners of management a sense of the importance of strategically leveraging social responsibility in the pharmaceutical industry, such that it provides a sustainable competitive advantage is that it requires a culture that can successfully execute a combination of activities. These firms should educate their employees towards the value‐added processes that accompany CSR‐based strategies. The internal as well as the external stakeholders of the pharmaceutical industry should also buy in the concepts of being socially responsible. CSR should be strongly supported in the company culture; thus including CSR in the training process of new employees and reinforcing the concepts to existing employees. Design/methodology/approach – A review of the applied literature on practices and actual examples of international firms with major headquarters in the Pittsburgh area have shown that innovative responsible strategy, exceeding government requirements and considering multiple stakeholders, as a long‐term objective. Findings – Case studies of GlaxoSmithKline and Bayer Corporation, which are two of the world's leading research‐based pharmaceutical companies, highlight the need and practice for sound corporate social responsibility. Historically, a concentration on improved operational effectiveness and overcapacity created a temporary economic advantage accompanied by increased profit and firm value. Such an advantage is short‐lived; investors may be satisfied, but competing companies will eventually mimic technological and material improvements. Practical implications – It is particularly difficult for pharmaceutical companies to allocate its strategic resources necessary to CSR strategies, due to so much of its funds are allocated for R&D and promotional activities, which are relatively risky in nature. The demand for its products is based on consumer motivation, which can vary greatly amongst different countries depending on the responsibilities of consumers, government and economies, and insurance companies or a mix of the three.. Originality/value – The pharmaceutical industry is under immense pressure by external and internal stakeholders with hopes of developing and distributing drugs efficiently. The pharmaceutical companies and their lobbyists command considerable influence on healthcare initiatives by governmental agencies and must continually emphasize effort and investments in R&D in order to compete in the industry on a global perspective. The pharmaceutical industry must take into account the ability to be socially responsible to the external stakeholders. The prolonged advantage of corporate social responsibility ensures sustainable economic advantage of any organization.
The end of shareholder value thinking
Authors: de Waal André
Published: November 2008

Purpose

The purpose of this paper is to discuss a trend in business strategy thinking which has been detrimental to the continuity of organizations, so that managers will reevaluate where they should aim their efforts at in respect to improving their organizations.

Design/methodology/approach

The research is based on a literature study, the outcomes of the current debate between the Anglo‐American and the European strategy thinking movements, and numerous discussions during workshops with management teams.

Findings

In line with the findings of current high performance organizations research, a long term focus of management is one of the most important capabilities management has to develop in order to safeguard the continuity of the organization.

Practical implications

In lieu of the scandals that rocked the business world these last two decades and looking at the main task of management – safeguarding the continuity of the organization by making sure the organization earns its place in society, replacing shareholder value thinking with shareholder value thinking is highly recommended.

Originality/value

This paper contributes to the ongoing debate on how to make organizations more corporate responsible.
CD40 ligation restores type 1 polarizing capacity in TLR4‐activated dendritic cells that have ceased interleukin‐12 expression
Authors: Michael Dohnal Alexander , Luger Romana , Paul Petra , Fuchs Dietmar , Felzmann Thomas
Published: November 2008

Inflammation triggered by microbial lipopolysaccharide (LPS) through Toll‐like receptor (TLR) 4 in the presence of interferon (IFN)‐γ induces cytokine secretion in dendritic cells (DCs) tightly regulated by a defined differentiation program. This DC differentiation is characterized not only by a dynamic immune activating but also by tolerance‐inducing phenotype associated with down‐modulation of cytokines previously considered to be irreversible. CD40L on activated T cells further modifies DC differentiation. Using DNA micro‐arrays, we showed down‐regulated mRNA levels of TLR signalling molecules, whereas CD40/CD40L signalling molecules were up‐regulated at a time when LPS/IFN‐γ‐activated DCs had ceased cytokine expression. Accordingly, we demonstrated that CD40/CD40L but not TLR4 or TLR3 signalling mediated by LPS or poly (cytidylic‐inosinic) acid (poly I:C) and dsRNA re‐established the capacity for secreting interleukin (IL)‐12 in primarily LPS/IFN‐γ‐activated DCs, which have exhausted their potential for cytokine secretion. The resulting TH1 polarizing DC phenotype – which lacked accompanying secretion of the crucial immune suppressive factor IL‐10 – maintained the potential for activation of cytotoxic T lymphocytes (CTLs). We therefore conclude that immune modulation is restricted to a secondary T‐cell‐mediated stimulus at an exhausted DC state, which prevents an immune tolerant DC phenotype. These findings impact on the rational design of TLR‐activated DC‐based cancer vaccines for the induction of anti‐tumoural CTL responses.
MicroRNA‐223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells
Authors: Yuan Jin‐Yun , Wang Fang , Yu Jia , Yang Gui‐Hua , Liu Xiao‐Ling , Zhang Jun‐Wu
Published: November 2008

MicroRNAs (miRNAs) are thought to modulate a variety of cellular events. Several studies have revealed the functions of miR‐223 in granulopoiesis. Here we analysed miR‐223 expression in various human tissues, blood and leukaemia cells, and focused on its role in K562 erythroid and megakaryocytic differentiation. MiR‐223 was detected not only in granulocytes but also in erythroid cells. In K562 cells, expression of miR‐223 was down‐regulated during haemin‐induced erythroid differentiation but up‐regulated during phorbol myristate acetate (PMA)‐induced megakaryocytic differentiation. The overexpression of miR‐223 resulted in significant decrease of γ‐globin mRNA and the fraction of benzidine‐positive cells in K562 cells, suggesting a suppressive effect of miR‐223 on erythroid differentiation. Peaks corresponding to 4N cells in stable transfectants overexpressing miR‐223 were higher than that in control K562 cells during megakaryocytic differentiation, indicating that miR‐223 increases megakaryocytic differentiation. The expression of LIM domain only 2 (LMO2) reporter was suppressed in NIH‐3T3 when the expression of miR‐223 was enforced by both the luciferase and fluorescence system. Furthermore, LMO2 mRNA and protein levels were significantly decreased in stable K562 transfectants overexpressing miR‐223. These results indicate that LMO2 is a direct target of miR‐223. Thus, our results suggest that miR‐223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells via down‐modulation of LMO2.
Visualizing CTL/melanoma cell interactions: multiple hits must be delivered for tumour cell annihilation
Authors: Caramalho Íris , Faroudi Mustapha , Padovan Elisabetta , Müller Sabina , Valitutti Salvatore
Published: November 2008

It is well established that cytotoxic T lymphocytes (CTL) can kill target cells offering a very small number of specific peptide/MHC complexes (pMHC). It is also known that lethal hit delivery is a very rapid response that occurs within a few minutes after cell–cell contact. Whether cytotoxicity is efficient and rapid in the context of CTL interaction with target cells derived from solid tumours is still elusive. We addressed this question by visualizing the dynamics of human CTL interaction with melanoma cells and their efficiency in eliciting cytotoxicity. Our results show that in spite of CTL activation to lethal hit delivery, killing of melanoma cells is not efficient. Time‐lapse microscopy experiments demonstrate that individual CTL rapidly polarize their lytic machinery towards target cells, yet the apoptotic process in melanoma cells is defective or ‘delayed’ as compared to conventional targets. These results indicate that although CTL activation to lethal hit delivery can be viewed as a ‘digital’ phenomenon rapidly triggered by a few ligands, melanoma cell annihilation is an ‘analogue’ response requiring multiple hits and prolonged contact time.
Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans
Authors: Van Der Loo Bernd , Schildknecht Stefan , Zee Rebecca , Bachschmid Markus M.
Published: November 2008

Ageing is an important risk factor for the development of cardiovascular diseases. Vascular ageing is mainly characterized by endothelial dysfunction, an alteration of endothelium‐dependent signalling processes and vascular remodelling. The underlying mechanisms comprise increased production of reactive oxygen species (ROS), inactivation of nitric oxide (·NO) and subsequent formation of peroxynitrite (ONOO−). Elevated ONOO− may exhibit new messenger functions by post‐translational oxidative modification of intracellular regulatory proteins. Mitochondria are a major source of age‐associated superoxide formation, as electrons are misdirected from the respiratory chain. Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is an integral part of the nucleoids and may protect mitochondrial DNA from ROS. A model linking ·NO, mitochondria, MnSOD and its acetylation/deacetylation by sirtuins (NAD+‐dependent class III histone deacetylases) may be the basis for a potentially new powerful therapeutic intervention in the ageing process.
Influence of prior sprint exercise on the parameters of the ‘all‐out critical power test’ in men
Authors: Vanhatalo Anni , Jones Andrew M.
Published: November 2008

We tested the hypothesis that a prior 30 s sprint exercise bout would significantly reduce the curvature constant (W′) but not the power‐asymptote (critical power, CP) of the power–duration relationship as assessed using a novel 3 min all‐out cycling test. Seven physically active male subjects completed the 3 min all‐out test on three occasions in random order: following no prior sprint exercise (control, C); following a 30 s sprint and a 2 min recovery (S2); and following a 30 s sprint and a 15 min recovery period (S15). The CP was estimated from the mean power output sustained over the final 30 s of the test and the W′ was estimated as the power–time integral above the end‐test power. There were no significant differences in the estimated CP between the control 3 min all‐out trial and the two prior sprint conditions (C, 235 ± 44 W; S2, 223 ± 46 W; and S15, 232 ± 50 W; P > 0.05; coefficients of variation 2, 3 and 6% for C–S2, C–S15 and S2–S15, respectively). However, the W′ in S2 (16.5 ± 3.3 kJ) was significantly lower than in C (20.8 ± 3.9 kJ) and S15 (21.2 ± 4.5 kJ; P < 0.05). The total work done was lower in S2 than in the other conditions (S2, 56.4 ± 7.2 kJ; C, 63.5 ± 6.6 kJ; and S15, 63.0 ± 6.0 kJ; P < 0.05). The W′, but not the CP, is sensitive to a bout of prior sprint exercise which would be expected to result in significant muscle phosphocreatine depletion. These findings support the fundamental principles of the power–duration relationship as applied to all‐out exercise.
F1C Fimbriae Play an Important Role in Biofilm Formation and Intestinal Colonization by the
Escherichia coli
Commensal Strain Nissle 1917
Authors: Lasaro Melissa A. , Salinger Nina , Zhang Jing , Wang Yantao , Zhong Zhengtao , Goulian Mark , Zhu Jun
Published: November 2008

Bacterial biofilm formation is thought to enhance survival in natural environments and during interaction with hosts. A robust colonizer of the human gastrointestinal tract,
Escherichia coli
Nissle 1917, is widely employed in probiotic therapy. In this study, we performed a genetic screen to identify genes that are involved in Nissle biofilm formation. We found that F1C fimbriae are required for biofilm formation on an inert surface. In addition, these structures are also important for adherence to epithelial cells and persistence in infant mouse colonization. The data suggest a possible connection between Nissle biofilm formation and the survival of this commensal within the host. Further study of the requirements for robust biofilm formation may improve the therapeutic efficacy of Nissle 1917.
Functional Analysis of MmeI from Methanol UtilizerMethylophilus methylotrophus, a Subtype IIC Restriction-Modification Enzyme Related to Type I Enzymes
Authors: Nakonieczna Joanna , Kaczorowski Tadeusz , Obarska-Kosinska Agnieszka , Bujnicki Janusz M.
Published: November 2008

MmeI fromMethylophilus methylotrophusbelongs to the type II restriction-modification enzymes. It recognizes an asymmetric DNA sequence, 5′-TCCRAC-3′ (R indicates G or A), and cuts both strands at fixed positions downstream of the specific site. This particular feature has been exploited in transcript profiling of complex genomes (using serial analysis of gene expression technology). We have shown previously that the endonucleolytic activity of MmeI is strongly dependent on the presence ofS-adenosyl-l-methionine (J. Nakonieczna, J. W. Zmijewski, B. Banecki, and A. J. Podhajska, Mol. Biotechnol. 37:127-135, 2007), which puts MmeI in subtype IIG. The same cofactor is used by MmeI as a methyl group donor for modification of an adenine in the upper strand of the recognition site toN6-methyladenine. Both enzymatic activities reside in a single polypeptide (919 amino acids [aa]), which puts MmeI also in subtype IIC of the restriction-modification systems. Based on a molecular model, generated with the use of bioinformatic tools and validated by site-directed mutagenesis, we were able to localize three functional domains in the structure of the MmeI enzyme: (i) the N-terminal portion containing the endonucleolytic domain with the catalytic Mg2+-binding motif D70-X9-EXK82, characteristic for the PD-(D/E)XK superfamily of nucleases; (ii) a central portion (aa 310 to 610) containing nine sequence motifs conserved amongN6-adenine γ-class DNA methyltransferases; (iii) the C-terminal portion (aa 610 to 919) containing a putative target recognition domain. Interestingly, all three domains showed highest similarity to the corresponding elements of type I enzymes rather than to classical type II enzymes. We have found that MmeI variants deficient in restriction activity (D70A, E80A, and K82A) can bind and methylate specific nucleotide sequence. This suggests that domains of MmeI responsible for DNA restriction and modification can act independently. Moreover, we have shown that a single amino acid residue substitution within the putative target recognition domain (S807A) resulted in a MmeI variant with a higher endonucleolytic activity than the wild-type enzyme.
Intestine and Environment of the Chicken as Reservoirs for Extraintestinal Pathogenic
Escherichia coli
Strains with Zoonotic Potential
Authors: Ewers Christa , Antão Esther-Maria , Diehl Ines , Philipp Hans-C. , Wieler Lothar H.
Published: November 2008

Although research has increasingly focused on the pathogenesis of avian pathogenic
Escherichia coli
(APEC) infections and the “APEC pathotype” itself, little is known about the reservoirs of these bacteria. We therefore compared outbreak strains isolated from diseased chickens (
n
= 121) with nonoutbreak strains, including fecal
E. coli
strains from clinically healthy chickens (
n
= 211) and strains from their environment (
n
= 35) by determining their virulence gene profiles, phylogenetic backgrounds, responses to chicken serum, and in vivo pathogenicities in a chicken infection model. In general, by examining 46 different virulence-associated genes we were able to distinguish the three groups of avian strains, but some specific fecal and environmental isolates had a virulence gene profile that was indistinguishable from that determined for outbreak strains. In addition, a substantial number of phylogenetic EcoR group B2 strains, which are known to include potent human and animal extraintestinal pathogenic
E. coli
(ExPEC) strains, were identified among the APEC strains (44.5%) as well as among the fecal
E. coli
strains from clinically healthy chickens (23.2%). Comparably high percentages (79.2 to 89.3%) of serum-resistant strains were identified for all three groups of strains tested, bringing into question the usefulness of this phenotype as a principal marker for extraintestinal virulence. Intratracheal infection of 5-week-old chickens corroborated the pathogenicity of a number of nonoutbreak strains. Multilocus sequence typing data revealed that most strains that were virulent in chicken infection experiments belonged to sequence types that are almost exclusively associated with extraintestinal diseases not only in birds but also in humans, like septicemia, urinary tract infection, and newborn meningitis, supporting the hypothesis that not the ecohabitat but the phylogeny of
E. coli
strains determines virulence. These data provide strong evidence for an avian intestinal reservoir hypothesis which could be used to develop intestinal intervention strategies. These strains pose a zoonotic risk because either they could be transferred directly from birds to humans or they could serve as a genetic pool for ExPEC strains.