bluuebunny/crossref_metadata_2025 huggingface dataset:
Selecting managers for transformational change
Authors: Doyle Mike
Published: August 2006

This article draws on the findings of a recent empirical study into the experience of managing change in ‘high velocity’, transformational change contexts. It argues that, with increasing empowerment, notions of the singular, mandated change agent may have to be juxtaposed with the idea of change being managed by a more diverse, multifarious ‘cast of characters’. If this is the case, effectiveness in change management may increasingly rest on the development and application of a systematic methodology for assessing the suitability and capabilities to perform in a change role. However, on the basis of the evidence presented, it would appear that selection decisions are being made on a largely subjective and arbitrary basis, and this may be creating wrong or misguided assumptions about an individual's suitability to perform in a change agent role. Additionally, the initial evidence suggests that the process of selection may be open to manipulation by some individuals whose personal aims and goals in the change process are not necessarily congruent with those of the organisation. This in turn may pose an element of strategic risk to the overall change process. The article then discusses some of the theoretical and practical implications facing those with a responsibility for selecting and managing the change managers.
Reconciling traditional Chinese management with high‐tech Taiwan
Authors: Hempel Paul S. , Chang Ching‐Yen Daphne
Published: August 2006

The traditional view of management culture among the overseas Chinese is that of an autocratic, paternalistic and centralised organisation with low levels of trust of ‘outside’ professional managers and employees. By contrast, the organisational culture associated with successful innovation and/or high technology is that of a decentralised organisation with high levels of employee autonomy. Existing research indicates that the overseas Chinese have become successful by sticking to the business sectors compatible with their preferred management culture, and that this holds true for Taiwan. What, then, explains the Taiwanese success in high‐technology ventures? This article offers initial evidence that management culture in Taiwan is adapting in order to enable industrial development in new areas. In‐depth interviews with 20 Taiwanese companies indicated that the change is being led by the high‐technology businesses. However, while many of these business culture changes are in a direction towards the organisational culture associated with high‐technology companies, it is also clear that a strong Chinese influence remains.
Communicating the psychological contract: an employer perspective
Authors: Guest David E. , Conway Neil
Published: August 2006

The concept of the psychological contract, with its focus on the exchange of perceived promises and commitments, is increasingly used as a framework to study the employment relationship. Yet research has predominantly focused on employee views and has largely neglected the organisational perspective and the management of the psychological contract. This article begins to redress the balance by reporting a study, based on a survey of 1,306 senior HR managers, that explores the management of the psychological contract and in particular the role of organisational communication. Three distinct and relevant aspects of organisational communication are identified, concerned with initial entry, day‐to‐day work and more future‐oriented, top‐down communication. Effective use of these forms of communication is associated with what managers judge to be a clearer and less frequently breached set of organisational promises and commitments, as well as with a fairer exchange and a more positive impact of policies and practices on employee attitudes and behaviour. The findings are discussed within the context of the wider literature on psychological contracts, organisational culture and HRM. The study confirms that the psychological contract offers managers a useful framework within which to consider and manage the employment relationship.
Paying the piper: choice and constraint in changing HR functional roles
Authors: Truss Catherine , Gratton Lynda , Hope‐Hailey Veronica , Stiles Philip , Zaleska Joanna
Published: August 2006

HR directors are often exhorted to play a more ‘strategic’ role in their organisations. However, it is not necessarily clear what is meant by this, or whether it is possible for departments to change their role at a whim. In this article we examine the changing role of the HR function within two contrasting organisations – an NHS trust and a bank – over a period of seven years. Drawing on role‐set theory and concepts of negotiated order, we illustrate how HR functional roles are located within a complex and dynamic social setting, and present a model that seeks to map these interrelationships.
Training and development deficiencies in ‘high skill’ sectors
Authors: Lloyd Caroline
Published: August 2006

Policy debates across advanced industrial economies are stressing the centrality of skills and training to compete in the new ‘knowledge economy’. In the UK increasing importance is being placed on improving workplace learning, yet policy has so far failed to confront the issue of employers' lack of investment in training and development. This article examines whether the high skill sectors that exist within the UK can provide a model of workplace learning for other such sectors to emulate. By using case study research from the aerospace and pharmaceutical industries, training and development practices are examined in relation to the requirements of the business and individual employees. The article will argue that the companies in question, despite their favourable product market position, remain constrained by the broader institutional environment.
Absence management and the issues of job retention and return to work
Authors: James Philip , Cunningham Ian , Dibben Pauline
Published: August 2006

Strategies aimed at facilitating the job retention and return to work of sick and injured workers are currently the subject of growing attention. In this article the authors examine the nature and potential significance of such strategies to absence management and utilise interview findings to shed light on current employer policies and practices relating to the management of long‐term absences. They conclude that at the national level a large proportion of working days lost through sickness absence stem from relatively long spells of absence and that the adoption of a proactive approach to supporting the return to work of ill and injured workers can have beneficial consequences. However, they further conclude that few organisations appear to have comprehensive arrangements in place to handle cases of long‐term absence. A number of areas where present employer arrangements could usefully be reviewed are therefore identified.
The legal aspects of teleworking
Authors: Baruch Yehuda , Smith Ian
Published: August 2006

This article discusses teleworking from a legal perspective. Although spreading rapidly, the many legal aspects of teleworking are under‐represented in the literature. The main issues covered in this article are the definition of teleworking, employment relationships and employment contracts, civil liability, and other legal considerations. Lastly, implications are discussed for both the management of organisations and the legal establishment.
Co‐determination and strategic integration in German firms
Authors: Wächter Hartmut , Muller‐Camen Michael
Published: August 2006

Looking at the economic development and importance of German companies in Europe, one might expect that an important aspect of a good economic performance is a well‐functioning HR system. Although a number of scholars claim this, the empirical evidence seems to point to the opposite. Several comparative studies have found that HRM in German companies is less strategically integrated and proactive than that of comparable firms in other countries. This article argues that the empirical results reported fail to grasp the essence of HRM in German firms. This lacuna is partly due to the co‐determination structure. HRM in large German firms has to be evaluated within the co‐determination structure, with the Betriebsrat (works council) being an important actor. For German firms co‐determination might even be a strategic resource. By examining this issue within such a framework, a more favourable picture of HR integration in German firms emerges.
Employee wellbeing in call centres
Authors: Holman David
Published: August 2006

Call centres are often perceived to have a negative impact on employee wellbeing, mainly attributed to four factors: job design, performance monitoring, HR practices and team leader support. This article reports on a survey of 557 customer service representatives that examined the relationship of these factors to four measures of wellbeing: anxiety, depression and intrinsic and extrinsic job satisfaction. One distinctive feature of this article is its focus on anxiety and depression, two major dimensions of wellbeing not addressed in call centre research to date. Results demonstrated that the factors most highly associated with wellbeing were high control over work methods and procedures, a low level of monitoring and a supportive team leader. Evidence also indicates that the level of wellbeing in some call centres is similar to that in other comparable forms of work.
New or traditional careers? A study of UK graduates' preferences
Authors: King Zella
Published: August 2006

Due to extensive changes to higher education in Britain, it is possible that graduates entering the labour market will have work experiences approximating to the ‘new’ career. We know little about whether this is a situation graduates are prepared for, or whether they welcome it. This article argues that a view about the changing nature of careers from the employee's perspective is needed. It describes some research investigating the career preferences and career self‐management of UK graduates in different organisational contexts, and provides evidence to suggest that graduates' endorsement of the ‘new’ career is limited. Employability is a key concern, but graduates expect to be able to develop that employability within the context of a traditional career. The article concludes by considering the implications for organisational career management, arguing that the traditional career still has considerable value for both employers and employees.
Too old or too young? The impact of perceived age discrimination
Authors: Snape Ed , Redman Tom
Published: August 2006

This article examines the impact on employee attitudes of perceived age discrimination, drawing on a study of a local authority. Survey respondents report that discrimination on the grounds of being ‘too young’ is at least as common as discrimination on the grounds of being ‘too old’. Findings suggest that perceived age discrimination, whether for being too old or too young, has negative consequences for affective commitment to the organisation. Those who feel that they have been discriminated against because they are considered too old have higher levels of continuance commitment. There is partial support for the hypothesis that older workers who feel that they have been discriminated against have a stronger intention to retire early.
The impact of HR practices on the performance of business units
Authors: Wright Patrick M. , Gardner Timothy M. , Moynihan Lisa M.
Published: August 2006

This article examines the impact of HR practices and organisational commitment on the operating performance and profitability of business units. Using a predictive design with a sample of 50 autonomous business units within the same corporation, the article reveals that both organisational commitment and HR practices are significantly related to operational measures of performance, as well as operating expenses and pre‐tax profits.
Challenging ‘strategic HRM’ and the relevance of the institutional setting
Authors: Paauwe Jaap , Boselie Paul
Published: August 2006

One of the more fundamental aspects of the ongoing debate about the added value of HRM relates to ‘best’ practice versus ‘best‐fit’. Best practice suggests the universal success of certain HR practices, while best‐fit acknowledges the relevant impact of contextual factors. We argue that differences in embeddedness and in institutional settings between, for example, countries affect the nature of HRM. To understand this phenomenon, we are in need of additional theory. In this article we will use the theory of new institutionalism as a better way to understand the shaping of HR policies and practices in different settings. After a concise review of the latest debates in the area of strategic HRM, in which the resource‐based view is the dominant perspective, we turn to an analysis of HRM in different institutional settings, which suggests the need for additional theory: ie new institutionalism. We offer propositions to explain the impact of different institutional mechanisms, including coercive, normative and mimetic ones, on the shaping of HR policies and practices in organisations. The remainder of the article then focuses on possible implications for practitioners, theoretical implications for future research, and challenges for strategic HRM.
Managing functional flexibility in a passenger transport firm
Authors: van der Velde Mandy , van den Berg Peter
Published: August 2006

In this study we focus on how a Dutch passenger transport firm managed the functional flexibility of employees when it had to become more flexible due to increased competition. Specifically, we examine the relationships between the personal characteristics of employees and their work perceptions on the one hand and their functional flexibility on the other. Our results show that functional flexibility consists of two dimensions, willingness and ability to be flexible, and that work perceptions are more closely related to the willingness, rather than the ability, to be flexible. Willingness to be flexible was positively related to need for growth, tendency for innovation, organisational support and negatively to task formalisation. Ability to be flexible was related to need for growth, tendency for innovation and general self‐efficacy. The implications for management are then discussed.
Survivors' reactions to downsizing: the importance of contextual factors
Authors: Sahdev Kusum
Published: August 2006

Downsizing has been a recurrent theme in corporate life for the last 20 years. Literature in this area has evolved sporadically and covers many aspects of it. Although this has resulted in rich data, there is a lack of robust research that integrates the strategic and operational elements of downsizing. Furthermore, downsizing results in negative outcomes such as loss of skills, learning and innovation. It can also result in negative emotions including anger, frustration and guilt. However, there is insufficient data about the specific conditions or contextual factors that influence survivors reactions. This article presents the findings of a study conducted in four large organisations in the UK that have undergone downsizing. It proposes a theoretical model encapsulating the organisational context, and argues that the two key factors that determine the context are frequency of downsizing and the degree of control that the organisation exercises in making the decision to downsize. A broad set of propositions is presented as to the likely reactions of ‘survivors’ in the various organisational contexts of downsizing.
Collectivism versus individualism in Dutch employment relations
Authors: De Leede Jan , Looise Jan Kees , Van Riemsdijk Maarten
Published: August 2006

From a very centralistic and collectivistic tradition after World War Two, Dutch employment relations now show a trend towards radical decentralisation and individualisation. What might be the consequences of this trend for labour relations? Do developments still fit within a movement towards ‘organised decentralisation’ or will the existing system of labour relations be hollowed out and destroyed? And what will be the consequences for ER management at company level? We present empirical data on how companies deal with their decentralised and individualised employment relations. It appears that, in the main areas such as labour contracts, working time arrangements, reward systems and development plans, decentralisation and individualisation are taking place. It has also become clear that management as well as workers support this and that a new form of negotiation between them is developing at workplace level, resulting in what we call ‘third contracts’ that are additional to the initial labour contract and the collective agreement. Our results also highlight the pragmatic way in which companies deal with these decentralised and individualised employment relations, which, nevertheless, remain linked to the national and collective levels of bargaining. Within the multilevel system of Dutch employment relations a new balance between collectivism and individualism is emerging.
Social embeddedness and job performance of tenured and non‐tenured professionals
Authors: Van Emmerik Hetty , Sanders Karin
Published: August 2006

This study examines how different employment relationships in academic settings, ie tenured versus non‐tenured appointments, are associated with different types of job performance efforts. The social embeddedness model contends that employees' efforts to perform well depend on embeddedness in the social environment. Adopting this perspective, we ask what types of embeddedness are likely to improve job performance efforts, namely compliance and contextual performance, under the condition of different employment relationships. Regression analyses on the responses of both tenured and non‐tenured faculty members show that employees' efforts to perform well can be explained by social embeddedness. Temporal embeddedness appears to be important in explaining the job performance efforts of tenured faculty members, while, in contrast, network embeddedness seems important in explaining the efforts of nontenured faculty members; and institutional embeddedness explained the efforts of both groups of faculty members.
Working to live or living to work? Work/life balance early in the career
Authors: Sturges Jane , Guest David
Published: August 2006

This article reports the findings of research that explored relationships between work/life balance, work/non‐work conflict, hours worked and organisational commitment among a sample of graduates in the early years of their career. It concludes that, although graduates seek work/life balance, their concern for career success draws them into a situation where they work increasingly long hours and experience an increasingly unsatisfactory relationship between home and work. The article discusses the causes and potential consequences of this predicament and in particular how work/non‐work conflict is linked to hours worked, the state of the psychological contract and organisational commitment. It highlights the role of organisations' policy and practice in helping to manage the relationship between work and non‐work and the development of organisational commitment through support for younger employees' lives out‐of‐work and effective management of aspects of the psychological contract.
The Perceived Value of College Physics Textbooks: Students and Instructors May Not See Eye to Eye
Authors: Podolefsky Noah , Finkelstein Noah
Published: August 2006

Physics instructors generally tell their students to read the textbook assignments before coming to lecture. While the textbook is a part of nearly every physics course, it is not clear how students use it. Only a small number of previous studies have asked how students actually use their textbooks. One such study measured the amount students read a particular introductory physics textbook at two institutions. This study showed that at one institution less than 40% of students in introductory physics regularly read the textbook assignments, but that at an institution where students were required to submit reading exercises, 55% of students regularly read the textbook.1 However, this study did not explore the effects of reading or whether different courses or different textbooks affected student reading habits. Another study, in chemistry, reported a significant correlation between the time spent reading and course grades for general chemistry students; lower performing students actually read more. This study, however, also reported that for organic chemistry students there was no correlation between time spent reading and course grades.2
Phylogenetic Analysis of Polyomavirus BK Sequences
Authors: Sharma Preety M. , Gupta Gaurav , Vats Abhay , Shapiro Ron , Randhawa Parmjeet
Published: August 2006

Polyomavirus BK (BKV) has emerged as an important pathogen in kidney transplant patients. Existing taxonomic classifications of BKV come from conventional DNA sequence alignments based on limited data derived from the VP1 gene. We have used a phylogenetic whole-genome approach to examine the pattern of diversity and evolutionary relationships between 45 BKV strains isolated from multiple clinical settings. This analysis supports the classification of BKV into six genotypes, of which types V and VI have not been previously recognized. BKV strains hitherto classified as type I are, in fact, quite heterogeneous, and several cluster with our newly defined genotypes V and VI. The sequence information needed for assigning genotypes can be captured by VP1, VP2, VP3, or large T-gene sequencing. The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific. Type-specific amino acid changes within the VP1 region are predicted to map to the BC and DE loops. The number of taxonomically informative amino acid changes in the large T antigen exceeds even that of the VP1 region. Viral strains isolated from healthy subjects and from patients with human immunodeficiency virus infection, Wiskott-Aldrich syndrome, and vasculopathy with capillary leak syndrome formed distinct subclusters. However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy.
An Immunoreceptor Tyrosine Activation Motif in the Mouse Mammary Tumor Virus Envelope Protein Plays a Role in Virus-Induced Mammary Tumors
Authors: Ross Susan R. , Schmidt John W. , Katz Elad , Cappelli Laura , Hultine Stacy , Gimotty Phyllis , Monroe John G.
Published: August 2006

Mouse mammary tumor virus (MMTV) induces breast cancer with almost 100% efficiency in susceptible strains through insertional activation of protooncogenes, such as members of thewntand fibroblast growth factor (fgf) families. We previously showed that expression of the MMTV envelope protein (Env) in normal immortalized mammary epithelial cells grown in three-dimensional cultures caused their morphological transformation, and that this phenotype depended on an immunoreceptor tyrosine-based activation motif (ITAM) present in Env and signaling through the Syk tyrosine kinase (E. Katz, M. H. Lareef, J. C. Rassa, S. M. Grande, L. B. King, J. Russo, S. R. Ross, and J. G. Monroe, J. Exp. Med.201:431-439, 2005). Here, we examined the role of the Env protein in virus-induced mammary tumorigenesis in vivo. Similar to the effect seen in vitro, Env expression in the mammary glands of transgenic mice bearing either full-length wild-type provirus or only Env transgenes showed increased lobuloalveolar budding. Introduction of the ITAM mutation into theenvof an infectious, replication-competent MMTV or into MMTV/murine leukemia virus pseudotypes had no effect on incorporation of Env into virus particles or on in vitro infectivity. Moreover, replication-competent MMTV bearing the ITAM mutation in Env infected lymphoid and mammary tissue at the same level as wild-type MMTV and was transmitted through milk. However, mammary tumor induction was greatly attenuated, and the pattern of oncogene activation was altered. Taken together, these studies indicate that the MMTV Env protein participates in mammary epithelial cell transformation in vivo and that this requires a functional ITAM in the envelope protein.
Histatin 5-Derived Peptide with Improved Fungicidal Properties Enhances Human Immunodeficiency Virus Type 1 Replication by Promoting Viral Entry
Authors: Groot Fedde , Sanders Rogier W. , ter Brake Olivier , Nazmi Kamran , Veerman Enno C. I. , Bolscher Jan G. M. , Berkhout Ben
Published: August 2006

Antimicrobial peptides are found in a number of body compartments and are secreted at mucosal surfaces, where they form part of the innate immune system. Many of these small peptides have a broad spectrum of inhibitory activity against bacteria, fungi, parasites, and viruses. Generally, the peptide's mode of action is binding and disruption of membranes due to its amphipathic properties. Histatin 5 is a salivary peptide that inhibits
Candida albicans
, an opportunistic fungus that causes oropharyngeal candidiasis in a majority of human immunodeficiency virus type 1 (HIV-1)-infected patients progressing towards AIDS. Previously, we increased the fungicidal properties of histatin 5 by replacing amino acids in the active domain of histatin 5 (Dh-5) (A. L. Ruissen, J. Groenink, E. J. Helmerhorst, E. Walgreen-Weterings, W. van’t Hof, E. C. Veerman, and A. V. Nieuw Amerongen, Biochem. J.
356:
361-368, 2001). In the current study, we tested the anti-HIV-1 activity of Dh-5 and its derivatives. Although Dh-5 inhibited HIV-1 replication, none of the peptide variants were more effective in this respect. In contrast, one of the derivatives, Dhvar2, significantly increased HIV-1 replication by promoting the envelope-mediated cell entry process. Most likely, Dhvar2 affects membranes, thereby facilitating fusion of viral and cellular membranes. This study shows that modification of antimicrobial peptides in order to improve their activity against a pathogen may have unpredictable and unwanted side effects on other pathogens.
Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and
vif
Genetic Variation
Authors: Pace Craig , Keller Jean , Nolan David , James Ian , Gaudieri Silvana , Moore Corey , Mallal Simon
Published: August 2006

APOBEC3G and APOBEC3F restrict human immunodeficiency virus type 1 (HIV-1) replication in vitro through the induction of G→A hypermutation; however, the relevance of this host antiviral strategy to clinical HIV-1 is currently not known. Here, we describe a population level analysis of HIV-1 hypermutation in near-full-length clade B proviral DNA sequences (
n
= 127). G→A hypermutation conforming to expected APOBEC3G polynucleotide sequence preferences was inferred in 9.4% (
n
= 12) of the HIV-1 sequences, with a further 2.4% (
n
= 3) conforming to APOBEC3F, and was independently associated with reduced pretreatment viremia (reduction of 0.7 log
10
copies/ml;
P
= 0.001). Defective
vif
was strongly associated with HIV-1 hypermutation, with additional evidence for a contribution of
vif
amino acid polymorphism at residues important for APOBEC3G-
vif
interactions. A concurrent analysis of APOBEC3G polymorphism revealed this gene to be highly conserved at the amino acid level, although an intronic allele (6,892 C) was marginally associated with HIV-1 hypermutation. These data indicate that APOBEC3G-induced HIV-1 hypermutation represents a potent host antiviral factor in vivo and that the APOBEC3G-
vif
interaction may represent a valuable therapeutic target.
Cross-Interaction between JC Virus Agnoprotein and Human Immunodeficiency Virus Type 1 (HIV-1) Tat Modulates Transcription of the HIV-1 Long Terminal Repeat in Glial Cells
Authors: Kaniowska Dorota , Kaminski Rafal , Amini Shohreh , Radhakrishnan Sujatha , Rappaport Jay , Johnson Edward , Khalili Kamel , Del Valle Luis , Darbinyan Armine
Published: August 2006

The human polyomavirus JC virus (JCV) is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), which is commonly seen in AIDS patients. The bicistronic viral RNA, which is transcribed at the late phase of infection, is responsible for expressing the viral capsid proteins and a small regulatory protein, agnoprotein. Immunohistochemical analysis of brain tissue from subjects with AIDS/PML revealed colocalization of the human immunodeficiency virus type 1 (HIV-1) transactivator, Tat, and JCV agnoprotein in nucleus and cytoplasm of “bizarre” astrocytes. In accord with this observation, we detected the copresence of agnoprotein and Tat in human astrocytes upon infection with JCV and HIV-1 or in astrocytic cells expressing these proteins after transfection. Interestingly, results from infection of human astrocytes with HIV-1 and JCV showed a decrease in the level of HIV-1 replication in cells that are coinfected with JCV. Conversely, a slight increase in the level of JCV replication was observed in the presence of HIV-1. The copresence of JCV and HIV-1 in astrocytes prompted us to investigate the possible cross-interaction of agnoprotein with Tat and its impact on HIV-1 gene transcription. Our results demonstrate that agnoprotein through its N-terminal domain associates with Tat and the interaction causes the suppression of Tat-mediated enhancement of HIV-1 promoter activity in these cells. Results from RNA and protein binding assays showed that agnoprotein can inhibit the association of Tat with its target RNA sequence, TAR, and with cyclin T1. Furthermore, agnoprotein is able to interfere with cross-interaction of Tat with the p65 subunit of NF-κB and Sp1, whose functions are critical for Tat activation of the long terminal repeat. These observations unravel a new pathway for the molecular interaction of these two viruses in biologically relevant cells in the brains of AIDS/PML patients.
Does stretching increase ankle dorsiflexion range of motion? A systematic review
Authors: Radford J A , Burns J , Buchbinder R , Landorf K B , Cook C
Published: August 2006

Background:Many lower limb disorders are related to calf muscle tightness and reduced dorsiflexion of the ankle. To treat such disorders, stretches of the calf muscles are commonly prescribed to increase available dorsiflexion of the ankle joint.

Hypothesis:To determine the effect of static calf muscle stretching on ankle joint dorsiflexion range of motion.

Study design:A systematic review with meta-analyses.

Methods:A systematic review of randomised trials examining static calf muscle stretches compared with no stretching. Trials were identified by searching Cinahl, Embase, Medline, SportDiscus, and Central and by recursive checking of bibliographies. Data were extracted from trial publications, and meta-analyses performed that calculated a weighted mean difference (WMD) for the continuous outcome of ankle dorsiflexion. Sensitivity analyses excluded poorer quality trials. Statistical heterogeneity was assessed using the quantityI2.

Results:Five trials met inclusion criteria and reported sufficient data on ankle dorsiflexion to be included in the meta-analyses. The meta-analyses showed that calf muscle stretching increases ankle dorsiflexion after stretching for ⩽15 minutes (WMD 2.07°; 95% confidence interval 0.86 to 3.27), >15–30 minutes (WMD 3.03°; 95% confidence interval 0.31 to 5.75), and >30 minutes (WMD 2.49°; 95% confidence interval 0.16 to 4.82). There was a very low to moderate statistical heterogeneity between trials. The meta-analysis results for ⩽15 minutes and >15–30 minutes of stretching were considered robust when compared with sensitivity analyses that excluded lower quality trials.

Conclusions:Calf muscle stretching provides a small and statistically significant increase in ankle dorsiflexion. However, it is unclear whether the change is clinically important.
ON THE CASIMIR EFFECT FOR PARALLEL PLATES IN THE SPACETIME WITH ONE EXTRA COMPACTIFIED DIMENSION
Authors: CHENG HONGBO
Published: August 2006

In this paper, the Casimir effect for parallel plates in the presence of one compactified universal extra dimension is re-examined in detail. Having regularized the expressions of Casimir force, we show that the nature of Casimir force is repulsive if the distance between the plates is large enough, which does not agree with the experimental phenomena.
NEUTRINO MASS MATRIX FROM Δ(27) SYMMETRY
Authors: MA ERNEST
Published: August 2006

The discrete subgroup Δ(27) of SU(3) has some interesting properties which may be useful for understanding charged-lepton and neutrino mass matrices. Assigning leptons to the 3 and [Formula: see text] representations of Δ(27), a simple form of the Majorana neutrino mass matrix is obtained and compared to present data.
QUANTUM MONTE CARLO SIMULATIONS OF FERMIONS: A MATHEMATICAL ANALYSIS OF THE FIXED-NODE APPROXIMATION
Authors: CANCÈS ERIC , JOURDAIN BENJAMIN , LELIÈVRE TONY
Published: August 2006

The Diffusion Monte Carlo (DMC) method is a powerful strategy to estimate the ground state energy E0 of an N-body Schrödinger Hamiltonian H = -½Δ + V with high accuracy. It consists of writing E0 as the long-time limit of an expectation value of a drift-diffusion process with a source term, and numerically simulating this process by means of a collection of random walkers. As for a number of stochastic methods, a DMC calculation makes use of an importance sampling function ψI which hopefully approximates some ground state ψ0 of H. In the fermionic case, it has been observed that the DMC method is biased, except in the special case when the nodal surfaces of ψI coincide with those of a ground state of H. The approximation due to the fact that, in practice, the nodal surfaces of ψI differ from those of the ground states of H, is referred to as the Fixed Node Approximation (FNA). Our purpose in this paper is to provide a mathematical analysis of the FNA. We prove that, under convenient hypotheses, a DMC calculation performed with the importance sampling function ψI, provides an estimation of the infimum of the energy 〈ψ, Hψ〉 on the set of the fermionic test functions ψ that exactly vanish on the nodal surfaces of ψI.
IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3β pathways and inhibition of atrogin-1 mRNA
Authors: Dehoux Mischaël , Gobier Catherine , Lause Pascale , Bertrand Luc , Ketelslegers Jean-Marie , Thissen Jean-Paul
Published: August 2006

Myofibrillar protein loss occurring in catabolic situations is considered to be mediated by the release of proinflammatory cytokines and associated with a decrease in circulating and muscle levels of insulin-like growth factor I (IGF-I). In this paper, we investigated whether the C2C12 myotube atrophy caused in vitro by TNF-α/IFN-γ cytokines might be reversed by exogenous IGF-I. Our results showed that, despite the presence of TNF-α/IFN-γ, IGF-I retained its full ability to induce the phosphorylation of Akt, Foxo3a, and GSK-3β (respectively, 16-fold, 9-fold, and 2-fold) together with a decrease in atrogin-1 mRNA (−39%, P < 0.001). Although this ubiquitin ligase has been reported to accelerate the degradation of MyoD, a myogenic transcription factor driving the transcription of myosin heavy chain (MHC), IGF-I failed to blunt the reduction of MyoD and MHC caused by TNF-α/IFN-γ. Moreover, IGF-I only very slightly attenuated the myotube atrophy induced by TNF-α/IFN-γ (TNF-α/IFN-γ 15.48 μm alone vs. TNF-α/IFN-γ/IGF-I 16.97 μm, P < 0.001). In conclusion, our data show that IGF-I does not reverse the myotube atrophy induced by TNF-α/IFN-γ despite the phosphorylation of Foxo and GSK-3β and the downregulation of atrogin-1 mRNA. Our study suggests therefore that factors other than IGF-I decrease are responsible for the muscle atrophy caused by proinflammatory cytokines.
A retroviral expression system based on tetracycline-regulated tricistronic transactivator/repressor vectors for functional analyses of antiproliferative and toxic genes
Authors: Ausserlechner Michael J. , Obexer Petra , Deutschmann Andrea , Geiger Kathrin , Kofler Reinhard
Published: August 2006

Establishment of stably transfected mammalian cells with conditional expression of antiproliferative or proapoptotic proteins is often hampered by varying expression within bulk-selected cells and high background in the absence of the inducing drug. To overcome such limitations, we designed a gene expression system that transcribes the tetracycline-dependent rtTA2-M2-activator, TRSID-silencer, and selection marker as a tricistronic mRNA from a single retroviral vector. More than 92% of bulk-selected cells expressed enhanced green fluorescent protein or luciferase over more than three orders of magnitude in an almost linear, dose-dependent manner. To functionally test this system, we studied how dose-dependent expression of p27Kip1 affects proliferation and viability of SH-EP neuroblastoma cells. Low to moderate p27Kip1 expression caused transient G0-G1 accumulation without reduced viability, whereas high p27Kip1 levels induced significant apoptosis after 72 hours. This proves that this expression system allows concentration-dependent analysis of gene function and implicates p27Kip1 as a critical regulator of both proliferation and apoptosis in SH-EP neuroblastoma cells. [Mol Cancer Ther 2006;5(8):1927–34]
A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity
Authors: Law Benedict , Quinti Luisa , Choi Yongdoo , Weissleder Ralph , Tung Ching-Hsuan
Published: August 2006

A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC50 of r7-kla (3.54 ± 0.11 μmol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems. [Mol Cancer Ther 2006;5(8):1944–9]
Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity
Authors: Buck Elizabeth , Eyzaguirre Alexandra , Haley John D. , Gibson Neil W. , Cagnoni Pablo , Iwata Kenneth K.
Published: August 2006

Signaling through the receptor for epidermal growth factor receptor (EGFR) is frequently deregulated in solid tumors. Erlotinib (Tarceva, OSI-774, OSI Pharmaceuticals, Inc., Melville, NY) is a low molecular weight, orally bioavailable inhibitor of the EGFR that has been approved for both non–small cell lung cancer and pancreatic cancers. Previous studies have indicated that sensitivity to EGFR antagonists correlated with HER-3 signaling for non–small cell lung cancer. Herein, we have sought to understand the signaling pathways that mediate erlotinib sensitivity for pancreatic and colorectal cancers. In a panel of 12 pancreatic tumor cell lines, we find that EGFR is coexpressed with HER-3 in all cell lines sensitive to erlotinib but not in insensitive cell lines. Erlotinib can block HER-3 phosphorylation in these sensitive cell lines, suggesting that HER-3 is transactivated by EGFR. Knockdown of HER-3 in BxPC3, an erlotinib-sensitive pancreatic tumor cell line, results in inhibition of the phosphorylation for both Akt and S6 and is associated with a decrease in cell proliferation and reduced sensitivity to erlotinib. Therefore, EGFR transactivation of HER-3 mediates Akt signaling and can contribute to erlotinib sensitivity for pancreatic tumors. We extended our analysis to a panel of 13 colorectal tumor cell lines and find that, like pancreatic, HER-3 is coexpressed with EGFR in the most erlotinib-sensitive cell lines but not in erlotinib-insensitive cell lines. These studies suggest that HER-3 could be used as a biomarker to select patients who are most likely to respond to erlotinib therapy. [Mol Cancer Ther 2006;5(8):2051–9]
Preclinical evaluation of tumor microvascular response to a novel antiangiogenic/antitumor agent RO0281501 by dynamic contrast-enhanced MRI at 1.5 T
Authors: Muruganandham Manickam , Lupu Mihaela , Dyke Jonathan P. , Matei Cornelia , Linn Michael , Packman Kathryn , Kolinsky Kenneth , Higgins Brian , Koutcher Jason A.
Published: August 2006

Inhibition of tumor angiogenesis is a promising approach in cancer treatment. The purpose of this study was to evaluate the vascular response of human lung tumor xenografts in vivo to RO0281501, an inhibitor of tyrosine kinase receptors, including vascular endothelial growth factor receptor 2, fibroblast growth factor receptor, and platelet-derived growth factor receptor, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Human non–small cell lung carcinoma (H460a) xenografts grown s.c. in athymic nu/nu mice were treated p.o. with the antiangiogenic agent RO0281501. Treatment-induced changes in tumor volume, epiphyseal growth plate thickness, and microvessel density assessed by CD31 immunohistochemistry were analyzed. Tumor vascular permeability and perfusion were measured in tumors using DCE-MRI with gadopentetate dimeglumine on a 1.5 T clinical scanner to assess vascular function. Treatment with RO0281501 resulted in significant growth retardation of H460a tumors. RO0281501-treated tumors showed histologic evidence of growth plate thickening and relatively lower microvessel density compared with the controls. Regarding DCE-MRI variables, the initial slope of contrast uptake and Akep were significantly decreased on day 7 of treatment. RO0281501 is a novel antiangiogenic/antitumor agent, which is active in the H460a xenograft model. Its effects on tumor vasculature can be monitored and assessed by DCE-MRI on a 1.5 T human MR scanner with clinically available gadopentetate dimeglumine contrast, which will facilitate clinical trials with this or similar agents. [Mol Cancer Ther 2006;5(8):1950–7]
Antitumor immune response induced by i.t. injection of vector-activated dendritic cells and chemotherapy suppresses metastatic breast cancer
Authors: Akbulut Hakan , Tang Yucheng , Akbulut K. Gonca , Maynard Jonathan , Zhang Lixin , Deisseroth Albert
Published: August 2006

S.c. injection of the Ad-sig-tumor-associated antigen (TAA)/ecdCD40L vector vaccine has been shown to induce a CD8 immune response against TAA for up to 1 year. The first goal of this article is to test if the injection of autologous dendritic cells infected ex vivo with the Ad-sig-TAA/ecdCD40L can increase the immune response induced against TAA. The second goal is to test the effect of adding local chemotherapy in the form of i.t. injection of the AdCDIRESE1A vector-directed chemotherapy on the immune response induced by i.t. injection of adenoviral vector-activated dendritic cells. The results show that the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector, which encodes the cytosine deaminase chemotherapy sensitization transcription unit, to the i.t. injection of Ad-sig-ecdCD40L vector-infected dendritic cells increased the level of suppression of the growth of the CCL-51 breast cancer cells. The combination of i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector and Ad-sig-ecdCD40L vector-infected dendritic cells into s.c. CCL-51 breast cancer nodules suppressed the growth of uninjected metastatic tumor nodules in the lung. Finally, adding the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector to the i.t. administration of dendritic cells infected with a rat HER-2/neu (rH2N)–expressing vector (Ad-sig-rH2N/ecdCD40L) led to the induction of rH2N-specific antitumoral immunity in rH2N transgenic mice (which are anergic to the rH2N antigen). This anti-rH2N immune response suppressed the growth of established H2N-positive NT2 breast cancer more efficiently than did the vector-targeted chemotherapy or Ad-sig-rH2N/ecdCD40L-infected dendritic cell vaccine alone. [Mol Cancer Ther 2006;5(8):1975–85]
Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia
Authors: Efferth Thomas , Gillet Jean-Pierre , Sauerbrey Axel , Zintl Felix , Bertholet Vincent , de Longueville Françoise , Remacle Jose , Steinbach Daniel
Published: August 2006

A major issue in the treatment of T-cell acute lymphoblastic leukemia (T-ALL) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters. The majority of these proteins have not yet been examined in T-ALL. Using a newly developed microarray for the simultaneous quantification of 38 ABC transporter genes, we observed a consistent overexpression of ABCA2/ABCA3 in clinical samples of ALL. Therefore, we analyzed the association of these two genes with drug resistance. Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells. To study the causal relationship of ABCA2/A3 overexpression with drug resistance, we applied RNA interference (RNAi) technology. RNAi specific for ABCA2 or ABCA3 led to a partial decrease of expression in these two ABC transporters. Upon cotreatment of RNAi for ABCA2 with methotrexate and vinblastine, a partial decrease of ABCA2 expression as well as a simultaneous increase of ABCA3 expression was observed. Vice versa, ABCA3 RNAi plus drugs decreased ABCA3 and increased ABCA2 expression. This indicates that down-regulation of one ABC transporter was compensated by the up-regulation of the other. Application of RNAi for both ABCA2 and ABCA3 resulted in a more efficient reduction of the expression of both transporters. As a consequence, a significant sensitization of cells to cytostatic drugs was achieved. In conclusion, ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance. [Mol Cancer Ther 2006;5(8):1986–94]
Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin
Authors: Hamelers Irene H.L. , van Loenen Esther , Staffhorst Rutger W.H.M. , de Kruijff Ben , de Kroon Anton I.P.M.
Published: August 2006

Platinum-based drugs are widely used in cancer chemotherapy. However, their clinical use is limited by systemic toxicity, rapid blood clearance, and the occurrence of resistance. Our research is aimed at increasing the therapeutic index of these drugs by encapsulation in a lipid formulation. Previously, we developed a method for efficient encapsulation of cisplatin in a lipid formulation, yielding cisplatin nanocapsules. Here, we show that carboplatin, a cisplatin-derived anticancer drug with different chemical properties, can be efficiently encapsulated in a lipid formulation by a similar method. The carboplatin nanocapsules exhibit a very high cytotoxicity in vitro: the IC50 value of carboplatin nanocapsules is up to a 1,000-fold lower than that of conventional carboplatin when tested on a panel of carcinoma cell lines. Cellular platinum content analysis and confocal fluorescent imaging of the interaction of the carboplatin nanocapsules with IGROV-1 cells indicate that the improved cytotoxicity is due to increased platinum accumulation in the cells, resulting from uptake of the formulation by endocytosis. [Mol Cancer Ther 2006;5(8):2007–12]