bluuebunny/crossref_metadata_2025 huggingface dataset:
The Deployment of Untried Technology: British Naval Tactics in the Ironclad Era
Authors: Allen Matthew
Published: June 2008

In the ironclad navy there was powerful support for simplified systems of command and control in battle. Nonetheless, the complexity of the formations advocated for the simultaneous deployment of the gun, ram, and torpedo from ironclad battleships prevented a consensus on the appropriate system. So, while tactical doctrine remained a subject of dispute, seagoing admirals retained responsibility for their choice of tactics. Admiralty guidance was used only for training newly mobilized fleets. Tryon subsequently worked within this framework but was able to simplify his action signals because of the re-establishment of the primacy of the gun after the ironclad era.
Britain, the Middle East, and the `Northern Front', 1941—1942
Authors: Tamkin Nicholas
Published: June 2008

This article explores British plans for the defence of the `Northern Front' of the Middle Eastern theatre of war — Turkey, Syria, Iraq, and Iran — in the event of a German defeat of the Soviet Union in 1941—42. It demonstrates that, despite a traditional emphasis on the war in Libya and Egypt, the Northern Front mattered enormously to the British. Rather than undertaking to defend their ally Turkey against a German invasion, the British instead relied on Turkey to `defend us' while British armed forces prepared a fighting defence of the Middle East proper.
Baseline assessment of organizational capacity for health promotion within regional health authorities in Alberta, Canada
Authors: Anderson Donna , Raine Kim D. , Plotnikoff Ronald C. , Cook Kay , Barrett Linda , Smith Cynthia
Published: June 2008

This paper provides a baseline profile of organizational capacity for (heart) health promotion in Alberta's regional health authorities (RHAs); and examines differences in perceived organizational health promotion capacity specific to modifiable risk factors across three levels of staff and across capacity levels. Baseline data were collected from a purposive sample of 144 board members, senior/middle managers and service providers from 17 RHAs participating in a five-year time-series repeated survey design assessing RHA capacity for (heart) health promotion. Results indicate low levels of capacity to take health promotion action on the broader determinants of health and risk conditions like poverty and social support. In contrast, capacity for health promotion action specific to physiological and behavioural risk factors is considerably higher. Organizational “will” to do health promotion is noticeably more present than is both infrastructure and leadership. Both position held within an organization as well as overall level of organizational capacity appear to influence perceptions of organizational capacity. Overall, results suggest that organizational “will”, while necessary, is inadequate on its own for health promotion implementation to occur, especially in regard to addressing the broader determinants of health. A combination of low infrastructure and limited leadership may help explain a lack of health promotion action. (Promot Educ 2008;15(2): 6—14)
The health benefits of social mobilization: experiences with community-based Integrated Management of Childhood Illness in Chao, Peru and San Luis, Honduras
Authors: Harkins Thomas , Drasbek Christopher , Arroyo Juan , McQuestion Michael
Published: June 2008

This article reviews the implementation of the community component of the Integrated Management of Childhood Illness (IMCI) strategy in Chao, Peru (2001 to 2004) and San Luis, Honduras (2003 to 2005). An evaluation was conducted in 2005 and included a project documentation review, key-informant interviews, and a household level baseline and follow-up survey of the WHO/UNICEF key family practices in each intervention site. The promotion of the key family practices in Chao and San Luís demonstrated measurable success. In comparison with the initial survey in 2002, the percentage of participant mothers ( N = 78) in Chao in 2004 who knew that they should breastfeed exclusively for at least six months increased from 33% to 94%; the presentation of complete vaccination records for one-year-old children increased by 19%; the recognition of danger signs for pneumonia increased 18% and for diarrhea by 8%; and the percentage of mothers who received four or more prenatal check-ups increased by 25%. A dramatic reduction in malaria cases was also attributed to the intervention in Chao. In San Luis, a quasi-experimental, random household sample ( N = 300) showed that the incidence of diarrheal disease among children under five years old declined by 18% between survey rounds (from 44% in August 2004 to 26% in December 2005). Social mobilization has promoted inter-sector consensus-building around community health issues, especially those related to maternal and child health. The promotion of the participation of representatives from various organizations via the community IMCI social-actor methodology has led to increased civic cooperation. Positive changes in health behaviors have been documented through an increase in preventive health practices, greater demand for primary health care services, and concrete community actions to improve public health. (Promot Educ 2008;15(2): 15—20)
Health promotion competencies for Australia 2001—5: trends and their implications
Authors: Shilton Trevor , Howat Peter , James Ray , Burke Linda , Hutchins Cheryl , Woodman Richard
Published: June 2008

This important research builds on past projects in Australia and internationally that have sought to define and clarify competencies required to work in health promotion. The paper briefly explains the process undertaken in 2005 to update the Australian health promotion competencies as a collaboration of several leading health promotion agencies. The article reports findings from research undertaken in 2001 and 2005 and compares trends in perceptions of health promotion competencies across time. This dialogue among researchers, health promotion academics and practitioners can help to further the impact of competencies research on professional practice in health promotion globally. This project placed a priority on methodology that engaged the health promotion workforce in Australia. A two-stage process was employed including expert consultation with 39 senior health promotion professionals, followed by a modified Delphi process to engage 400 practitioners. Space was allowed for comment on the competencies including suggested word changes, and respondents were also invited to add additional competencies. The research involved a modified Delphi study where participants were invited to rate each competency as “essential”, “desirable” or “not relevant”, and to suggest changes to wording, as well as additions to the list. Responses were received from 400 practitioners and the results were presented and compared with the 2001 survey results. Results indicate a substantial shift in perceptions about health promotion practice in Australia during the initial years of the 21st century.The overall significant changes in perceptions indicate that by 2005 the Australian health promotion workforce had substantially moved away from an individual behaviour-dominated perception of health promotion practice. Increasing recognition was given to competencies that reflect environmental, economic and policy influences on health, and increased recognition that these processes are legitimate and essential components of the health promotion process. (Promot Educ 2008;15(2): 21—26)
The Ottawa Charter and acute health care
Authors: Munster Francesca
Published: June 2008

The Ottawa Charter is a significant document in relation to health promotion and the priorities for action needed to facilitate health for all people. The relevance of this document to an intensive care setting and the extent to which it may be translated into meaningful practice is examined in this paper. Acute care is an area lying at the extreme end of tertiary health, and at first glance it may be difficult to reconcile the significance of health promotion and the Ottawa Charter with this particular area of health care practice. On closer inspection, however, the relevance of the Charter lies in its impact on the number and type of patients seen in the Intensive Care Unit, and on the effect that the implementation of the health promotion action areas has on the client base. Even at the extreme end of tertiary care it is equally important to be aware of public health issues and to advocate, enable and mediate, where necessary, on behalf of and alongside patients, particularly as we care for them when they are most vulnerable. A commitment to both action and meaningful practice must continue to be pursued while equity in health remains a goal to be achieved. (Promot Educ 2008;15(2): 35—36)
The IUHPE Student and Early Career Network (ISECN): an update
Authors: Bull Torill , Corbin J. Hope
Published: June 2008

The year 2007 saw the birth of a new IUHPE baby: ISECN — the IUHPE Student and Early Career Network. This commentary presents some of the work that has been undertaken by ISECN this past year. We have appointed regional contacts, presented a poster about our network in a conference in Osaka, Japan, initiated a working group for communication with a specific focus on increasing equity in the way ISECN communicates with its members, launched a website (www.isecn.org), and held two global conference call meetings, connecting members from almost every corner of the planet. Also addressed in this Commentary is our role as Stream Managers for the IUHPE's new online offering, “Views on Health Promotion Online” and the formation of a working group to start developing a Code of Ethics for health promotion. These new projects will benefit ISECN, and contribute to the betterment of health promotion generally. All IUHPE members who are at the early stages of their careers are urged to join us. (Promot Educ 2008;15(2): 44-45)
Masculinité et lutte contre le sida en Afrique de l'Ouest: un modèle de formation
Authors: Vonarx Nicolas
Published: June 2008

Les liens qui existent entre l'identité masculine et l'épidémie du VIH sont de plus en plus reconnus. Qu'il s'agisse d'une identité de genre qui s'exprime à travers une multiplication des conquêtes sexuelles, à travers le manque de recours aux soins des hommes ou la gestion des rapports sexuels dominée par les hommes, ces liens obligent les organismes qui luttent contre le VIH à planifier des interventions avec les hommes. Davantage, pour être pertinentes, leurs interventions doivent aussi agir sur les hommes afin d'atteindre des modèles de masculinité, de changer des façons d'être héritées socialement et des comportements typiquement masculins. Inscrit dans ce processus d'intervention complexe qui est sensible aux rapports de genre et complémentaire des interventions classiques de santé publique, nous rappelons ici l'importance d'aborder le sujet de la masculinité dans la lutte contre le sida si on veut atteindre un fléau enraciné dans des réalités socioculturelles. À ce sujet, nous nous concentrons sur trois caractéristiques de masculinité problématiques dans l'épidémie du sida, soit: la domination masculine; une représentation des femmes véhiculée par les hommes; et la violence des hommes vis-à-vis des femmes. Dans un second temps, et à partir de travaux réalisés en Afrique de l'Ouest dans le cadre d'un projet de lutte contre le sida, nous partageons le contenu d'une formation dispensée à des intervenants locaux en précisant qu'il s'agit d'une étape préalable indispensable à la planification d'interventions avec et sur les hommes. Cette formation offre non seulement aux participants les moyens de comprendre les liens qui existent entre la masculinité et le sida, mais elle leur permet encore de situer cette problématique dans leur contexte de vie, de définir des priorités d'action et de commencer à élaborer des interventions sur le sujet. (Promot Educ 2008;15(2): 50-55)
Determinants of Home Death in Palliative Home Care: Using the interRAI Palliative Care to Assess End-of-Life Care
Authors: Brink Peter , Frise Smith Trevor
Published: June 2008

Many terminally ill patients are given the choice to die at home. This study identified determinants of home death among patients receiving palliative home care. Health information was collected using the interRAI palliative care assessment tool. The sample included health information from 536 patients receiving home health care from one community care access centre in Ontario, Canada. Patients who died at home were more likely to be functionally impaired and less likely to live alone. The patients' wish to die at home and the family's ability to cope were strong determinants of home death. This study suggests that the presence of a supportive family that is able to work with the health care team to implement a plan of care is important to the patients' ability to die at home. This study highlights the need to treat the patient and the caregiver(s) as a unit of care.
High-Dose Propofol Drip for Palliative Sedation: A Case Report
Authors: Herndon Christopher M. , Zimmerman Ethan
Published: June 2008

Oftentimes, patients at the end of life may present with challenging symptoms refractory to conventional therapies. Agitation and terminal restlessness, 2 common symptoms encountered in the hospice population, are frequently managed using benzodiazepines or typical antipsychotics. In clinical scenarios that either preclude their use or in which they prove ineffective, alternative pharmacotherapy must be considered. Propofol, a sedative-hypnotic unrelated to any other class of drug, may provide palliation of agitation and terminal restlessness refractory to benzodiazepines or antipsychotics. Here, the authors present a hospice patient admitted to the general medical floor of a small community hospital for pain and symptom management. A history of polysubstance abuse contributes to rapidly escalating doses of opioids and midazolam. Failure to control her symptoms resulted in the initiation and successful titration of propofol.
Preparing Head Start Personnel to Use a Curriculum-Based Assessment
Authors: Grisham-Brown Jennifer , Hallam Rena A. , Pretti-Frontczak Kristie
Published: June 2008

The purpose of this investigation was to evaluate technical assistance and training of Head Start teachers and assistant teachers on the use of a contemporary curriculum-based assessment. A description of the technical assistance process used and the procedures for determining interrater agreement and assessment fidelity are presented. During the study, participating practitioners reliably scored assessment protocols and administered the curriculum-based assessment with fidelity within their classrooms.
A Strategy-as-Practice Approach to Strategy Research and Education
Authors: Jarzabkowski Paula , Whittington Richard
Published: June 2008

This conclusion to the Dialog proposes a strategy-as-practice based approach to bringing strategy research and education closer to practice. Strategy-as-practice rejects the choice, proposed in the previous articles, between theory and practice. The authors argue for strategy research based rigorously on sociological theories of practice. Such research complements the parsimony and generalizability of economics-driven theory, extending strategy research to incorporate the messy realities of doing strategy in practice, with a view to developing theory that is high in accuracy. The authors suggest that practice-based research can also inform strategy teaching by providing students with rich case studies of strategy work as actually practiced, analyzed through such sociological lenses as ethnomethodology, dramaturgy, and institutional theory. Strategy-as-practice research does not aim to give students parsimonious models for analysis or expose them to cases of best practice but rather to help them develop practical wisdom through a better understanding of strategy in practice.
Why Strategy Teaching Should be Theory Based
Authors: Grant Robert M.
Published: June 2008

The rivalry between business policy and strategy analysis that played out at Harvard Business School during the 1980s remains an unresolved debate in strategic management teaching. I argue that developing managers with the knowledge and insight needed to make sound strategic decisions and guide the development of their organizations is best served by strategy teaching that is rooted in theory. My argument is based on my observations of how complex business situations are understood by the actors involved and the basis on which they form their judgments. To the extent that complex strategic situations are perceived through a cognitive framework, it is better such frameworks are derived from empirically validated theory than from folk wisdom, the gospel according to Warren Buffett, or an atheoretic classificatory system (such as SWOT analysis).
A Model for Selecting Product Ideas in Fuzzy Front End
Authors: Chang Houn-Wen , Wei Chiu-Chi , Lin Ru-Jen
Published: June 2008

The most decisive determinant that can create an enterprise's competitive advantage and core strength is the development of new products, and the extraction of the most potential product ideas in the fuzzy front end that can generate significant profits has become the vital concerns of research and development managers. However, the front end of the new product development project is composed of uncertainties, fuzziness, and complexities, which greatly hinder the success of product development and commercialization. This study proposes a rational and effective fuzzy multiple attribute group decision-making approach called product idea screening model for selecting new product ideas in the fuzzy front end, and aims to increase the possibility of successful product launch within limited resources and time pressure, especially, in this dramatic global changing environment.
Mapping Engineering Design Processes onto a Service-grid: Turbine Design Optimization
Authors: Goel Sanjay , Talya Shashishekara S. , Sobolewski Michael
Published: June 2008

This study presents an application of a distributed service-oriented architecture (FIPER) for the preliminary design of gas turbines. The FIPER architecture is based on the concept of registration and discovery of services in real time. It uses a service catalog that registers the services started on the network. These services are then discovered in real time from the grid and used in the design process. The turbine preliminary design process involves changing the configuration of the turbine incrementally and evaluating its performance using analysis (simulation) code. During the design process a one-dimensional analysis code is wrapped into a service using a standard interface developed in FIPER and launched on the network. Several such services were distributed across a grid of workstations. These services were then used to support the turbine configuration optimization process. The study presents the results of the optimization as well as the scalability characteristics of the service-grid.
Assessment Procedures for Narcissistic Personality Disorder
Authors: Miller Joshua D. , Campbell W. Keith , Pilkonis Paul A. , Morse Jennifer Q.
Published: June 2008

This study examined the degree of correspondence between two assessments for narcissistic personality disorder (NPD) in a mixed clinical and community sample—one using a self-report measure (Personality Diagnostic Questionnaire-4) and the other using clinical judgments derived from an assessment based on the longitudinal, expert, all data (LEAD) methodology. NPD scores demonstrated moderate convergence for the total scores but weak convergence for the individual criteria. The authors also examined the correlates created by each set of NPD scores using Cloninger's Temperament and Character Inventory (TCI). The NPD scores demonstrated areas of convergence (e.g., Cooperativeness, Self-directedness) and divergence (i.e., Harm Avoidance, Novelty Seeking) with these personality scores. These divergences may be due to the wording of certain items on the Personality Diagnostic Questionnaire-4 NPD scale, which may require rewriting if it is to provide an assessment that is more highly convergent with the Diagnostic and Statistical Manual of Mental Disorders NPD construct.
Idiopathic Factor VIII Inhibitor Autoantibody in a Man Presented After Accident
Authors: Mansouritorghabeh Hassan , Lak Manijeh , van Heerde Waander L.
Published: June 2008

Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of death from all causes of acquired hemophilia reaches up to 22%. In this article, the authors describe the case of a 55-year-old man who presented with unusual bleeding after an accident and the fluctuation of his hemostatic parameters during 13 months of follow-up. Initially he had 43 Bethesda unit (BU) inhibitor to factor VIII and <1% of factor VIII activity. The patient was given prednisone and azathioprine therapy (30 and 100 mg/day, respectively) for 4 months, but his hemostatic parameters did not improved during this phase. Then, 2 g cyclophosphamide was injected every 2 days, but no remarkable improvement was observed. Nine months later his inhibitor titers were high. The inhibitor and factor VIII concentrations were assessed 11 times during these 13 months, and the mean level of factor VIII inhibitor was 44 BU (with a minimum of 2 BU and a maximum of 103 BU); the minimum and maximum factor VIII concentrations were <1% and 20%, respectively. The patient experienced hemarthroses, severe epistaxis, hematoma, and gastrointestinal bleeding episodes during this phase. His factor VIII concentration spontaneously and gradually improved and increased to 51.5% 8 months after stopping the treatment with undetectable factor VIII inhibitor.
Diffuse Cerebral Infarct Associated With Factor V Leiden and Prothrombin 20210A Mutations in a Patient With Tetralogy of Fallot
Authors: Sipahi Tansu , Karademir Selmin , Kuybulu Ayça , Akar Nejat
Published: June 2008

A 2-year-old girl with tetralogy of Fallot presented with diffuse cranial infarct after cardiac angiography. Heterozygosity for factor V Leiden and prothrombin 20210A mutations were detected. The authors suggest that if thrombosis develops in patients with congenital heart disease, genetic risk factors should be evaluated.
An Analysis of the Impact of Diverse Forms of Childhood Psychological Maltreatment on Emotional Adjustment in Early Adulthood
Authors: Allen Brian
Published: June 2008

Recent research has documented the long-term mental health consequences of childhood psychological maltreatment; however, this research is limited in that it typically fails to recognize the qualitative differences of the various behaviors labeled as psychological maltreatment. This study examines the predictive ability of caregiver terrorizing, degradation, ignoring, and isolating during childhood on the self-reported occurrence of anxiety, depression, somatic complaints, and features of borderline personality disorder (BPD) in a sample of 256 university students between the ages of 18 and 22. Witnessing violence and childhood physical abuse are included in the analyses. Simultaneous regression analyses reveal that different forms of maltreatment emerge as predictors of the variables of emotional adjustment. Terrorizing predicted anxiety and somatic concerns, ignoring predicted scores of depression and features of BPD, and degradation predicted BPD features only. Findings suggest psychological maltreatment is a multifaceted construct requiring further research to investigate the long-term impact of various subtypes.
Screening Cases Within a Statewide Autism Registry
Authors: Goin-Kochel Robin P. , Cohen Robert
Published: June 2008

Parents and caregivers of 70 children enrolled in a university-based, statewide autism registry ( M age = 9.5 years) completed two questionnaires, one generated from criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition—Text Revision ( DSM-IV-TR) and the other the Social Communication Questionnaire (SCQ), to determine the number of cases likely to have autism. Based on DSM-IV-TR questionnaire ( DSM-Q) results, 94.3% met criteria for probable autism. In contrast, 88.6% met criteria for possible autism with the SCQ. The two instruments agreed on 89% of the cases, and the frequencies of cases meeting criteria on each measure were not statistically different ( p > .05). Results are discussed in terms of their application to the creation of local autism registries.
The Missing Child in Consumption Theory
Authors: Cook Daniel Thomas
Published: June 2008

Children are essentially invisible in theories of consumer society and culture, despite their presence and centrality in everyday life. In this article, I argue that children and childhood, and thus mothers and motherhood, must be acknowledged and investigated as constitutive of — rather than derivative of or exceptional to — commercial, consumer culture generally. The focus here is not on how to better accommodate children and childhood (and mothers and motherhood) within extant notions of consumption and consumer culture, but to begin to open up the field of consumption studies to the essential and non-negotiable presence of children and childhood throughout social life.
Marketing blackness
Authors: Crockett David
Published: June 2008

Marketing blackness, or black cultural identity, involves promotional strategies reliant on persons and other symbolic and material representations socially and historically constructed as black (e.g. speech and phonetic conventions, folklore, style, fashion, music, usage of the body, and the black physical form). This research presents a framework that assesses the strategic role blackness representations play in US advertising. The framework addresses the fundamental question of how advertisers use blackness representations to deliver promises about their products' benefits, a necessary first step in ultimately understanding their effectiveness and their impact on blackness itself. The framework orders blackness representations along two dimensions of meaning based on the central claims made in advertisements: (1) claims about the product/brand as a cultural resource, and (2) claims about the viewer that emphasize themes of similarity or difference. The framework also specifies a range of advertising strategies reliant on blackness representations located along the two dimensions. I suggest that the time has come to change the focus of research on blackness representations from numeric representation and role status to understanding their role in promotional strategy more broadly, particularly in branding.
The Meaning of Holiday Consumption
Authors: Therkelsen Anette , Gram Malene
Published: June 2008

Consumption objects are consumed not only for what they do but also for what they communicate and mean to oneself and one's surroundings, and hence they become part of consumers' identity formation processes. This article sets out to explore the meaning production and the identity construction taking place among mature tourists in connection with their holiday consumption. Identity construction is particularly interesting to study in the context of holidays as the physical crossing of borders also marks a mental crossing of borders, away from routines, obligations and scheduled time towards pleasure, free time and `the good life', and hence holidays are an obvious means of expressing `who I am'. Mature couples, who are in a phase of transition from full nester to empty nester and from employed individual to retired individual, are the focus. It is investigated in what way mature tourists use holidays as a vehicle of identity construction in their new life situation. In the existing literature, a strong focus is on individual consumers in relation to their creation of identity, and less on the role of identity creation in the gap between individual identity and the larger social groups with which people identify or from which they distinguish themselves. This article examines the locus of identity creation between `I' and `they': the `we'. The study is explorative in its approach.

The study shows that mature people use holidays for expressing who they are and, often just as importantly, who they are not. The couple is the central identifying unit and in the process of understanding their couple identity, the mature tourists use other couples and larger sociocultural entities to differentiate themselves from and affiliate with. Individual interests are also identified, but they are often staged as being in the interest of the couple and not just of the individual. Hence, the study demonstrates that the couple is a salient identifying unit in relation to holiday consumption among mature tourists.
A Comparison of Cognitive and Psychosocial Function for Males Within the ADHD Continuum
Authors: Padolsky Ilean
Published: June 2008

Two case studies are presented illustrating neurophysiological dysfunction suggesting input or output deficits in ADHD assessed across multiple domains. Data included child and family history, behavior ratings, information processing, speed, cognitive, neurophysiological, and academic function. Pretreatment data indicated impaired processing speed, excessive slow to fast wave ratios indicative of attentional disregulation, and poor psychosocial function evident in both children. Posttreatment assessment indicated improvement in slow to fast wave ratios and psychosocial functioning for both children. Additional improvement was also noted in cognitive and academic function in MH, the child with learning disabilities, and in processing speed for CX, the child with elevated cognitive function. Neurophysiological disregulation in ADHD may result in input or output impairment differentially affecting cognitive, academic, and psychosocial functioning. Heterogeneity within the ADHD continuum underscores the need for multifaceted assessment to guide diagnosis and treatment. In ADHD children nonresponsive to stimulants, neurofeedback can be a viable treatment to enhance attentional focus and on-task behavior.
Atomic number contrast in high angle annular dark field imaging of crystals
Authors: Findlay S. D. , Klenov D. O. , Stemmer S. , Allen L. J.
Published: June 2008

Quantitative comparisons between experimental and simulated high angle annular dark field (HAADF) images of SrTiO3, PbTiO3, InP and In0·53Ga0·47As in the scanning transmission electron microscope (STEM) are presented. Significant discrepancies are found in the signal to background ratios. For these strongly scattering samples, spatial incoherence and instabilities cannot account for the bulk of this discrepancy, as they could in previous explorations on silicon. The authors discuss where additional experiments and theoretical studies are needed for developing a quantitative understanding of HAADF image contrast.
Spectrum imaging and three-dimensional atom probe studies of fine particles in a vanadium micro-alloyed steel
Authors: Craven A. J. , MacKenzie M. , Cerezo A. , Godfrey T. , Clifton P. H.
Published: June 2008

Sub-15 nm vanadium based particles are one of the strengthening mechanisms in vanadium microalloyed high strength low alloy steel. Two analytical methods, spectrum imaging using electron energy loss spectroscopy (EELS) and three-dimensional atom probe, have been used to characterise such particles in the matrix, confirming the results of an earlier EELS study using extraction replicas where the particles were found to be N rich (V,Cr)(C,N). The present study also showed that the extraction efficiency of particles <4 nm is low. The three-dimensional atom probe showed an ‘atmosphere’ of segregated atoms around the cores of the particles and this was supported by the EELS results. In addition, it showed that the C concentration in the matrix was close to the equilibrium concentration at 600°C, supporting the explanation that the low C content of the particles was the result of Fe3C formation. Areas where the techniques can be further improved are identified.
Cross-correlative TEM and atom probe analysis of partial crystallisation in NiNbSn metallic glasses
Authors: Gorman B. P. , Puthucode A. , Diercks D. R. , Kaufman M. J.
Published: June 2008

Devitrification in a Ni60Nb35Sn5 bulk metallic glass alloy is investigated below the glass transition temperature using cross-correlative TEM and atom probe tomography. As cast and post-anneal (500°C for 2 h) specimens were analysed in both the TEM and the atom probe to determine the extent and nature of any phase separation in the as cast material or devitrification in the annealed material. Furthermore, it was of interest to determine the accuracy of the atom probe reconstructions of both types of material. No significant compositional partitioning was observed in the as cast state, suggesting an amorphous material, and the atom probe reconstructions of these specimens were found to be consistent with the TEM data. The annealed specimens contained Nb and Nb oxide rich regions, Ni3Sn nanocrystals, and a significant build-up of oxygen at the boundaries between these nanocrystals and the remaining amorphous matrix regions. These oxygen enriched regions are shown to result in anomalous atom probe reconstructions that are inconsistent with the TEM analyses. It is theorised that the initial crystallisation of Nb and Nb oxide rich regions results in NiSn rich regions, thereby resulting in the formation of Ni and Ni3Sn crystalline precipitates.
Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell–mediated effects on regulatory T cells
Authors: Hauben Ehud , Gregori Silvia , Draghici Elena , Migliavacca Barbara , Olivieri Stefano , Woisetschläger Maximilian , Roncarolo Maria Grazia
Published: June 2008

VAF347 is a low-molecular-weight compound, which activates the aryl hydrocarbon receptor (AhR). Herein, we report that oral administration of a water-soluble derivative of VAF347 (VAG539) promotes long-term graft acceptance and active tolerance in Balb/c mice that receive a transplant of MHC-mismatched pancreatic islet allografts. In vivo VAG539 treatment results in increased frequency of splenic CD4+ T cells expressing CD25 and Foxp3, markers associated with regulatory T (Tr) cells, and in vitro VAF347 treatment of splenic CD4+ T cells improved CD4+CD25+Foxp3+ T-cell survival. Interestingly, transfer of CD11c+ dendritic cells (DCs), but not of CD4+ T or CD19+ B cells, from VAG539-treated long-term tolerant hosts into mice that recently underwent transplantation resulted in donor (C57Bl/6)–specific graft acceptance and in a significantly higher frequency of splenic CD4+CD25+Foxp3+ Tr cells. Furthermore, the transfer of CD4+CD25+ T cells from these mice into mice that recently underwent transplantation promoted graft acceptance. Similarly, cell therapy with in vitro VAF347-treated bone marrow–derived mature DCs prevented islet graft rejection, and reduced OVA-specific T-cell responses in OVA-immunized mice. Collectively, our data indicate that AhR activation induces islet allograft–specific tolerance through direct as well as DC-mediated effects on Tr-cell survival and function.
The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes
Authors: Veldurthy Aditya , Patz Michaela , Hagist Susanne , Pallasch Christian P. , Wendtner Clemens-Martin , Hallek Michael , Krause Günter
Published: June 2008

Src family kinases (SFKs) were described to be overexpressed in chronic lymphocytic leukemia (CLL). We wished to examine the effects of the Src and Abl kinase inhibitor dasatinib on the intracellular signaling and survival of CLL cells. Dasa-tinib showed a dose- and time-dependent reduction of global tyrosine phosphorylation and of activating phosphotyrosine levels of SFKs. Treatment with 100 nM dasatinib led to decreased levels of the activated, phosphorylated forms of Akt, Erk1/2, and p38, and induced PARP cleavage through caspase activity. In Mec1 and JVM-3 cell lines, dasatinib increased p53 protein levels and inhibited proliferation. In freshly isolated CLL cells, dasatinib reduced the expression of Mcl-1 and Bcl-xL. Combination of 5 μM dasatinib and fludarabine increased the apoptosis induction of each by approximately 50%. In 15 primary CLL samples, cells with unmutated immunoglobulin variable heavy chain (IgVH) genes were more sensitive to dasatinib than those with mutated IgVH genes (P = .002). In summary, dasatinib shows potent inhibitory effects on the survival of CLL cells in vitro, most prominently in samples obtained from patients with unfavorable prognostic features.
β2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding
Authors: Takala Heikki , Nurminen Elisa , Nurmi Susanna M. , Aatonen Maria , Strandin Tomas , Takatalo Maarit , Kiema Tiila , Gahmberg Carl G. , Ylänne Jari , Fagerholm Susanna C.
Published: June 2008

Leukocyte integrins of the β2 family are essential for immune cell-cell adhesion. In activated cells, β2 integrins are phosphorylated on the cytoplasmic Thr758, leading to 14-3-3 protein recruitment to the β2 integrin. The mutation of this phosphorylation site impairs cell adhesion, actin reorganization, and cell spreading. Thr758 is contained in a Thr triplet of β2 that also mediates binding to filamin. Here, we investigated the binding of filamin, talin, and 14-3-3 proteins to phosphorylated and unphosphorylated β2 integrins by biochemical methods and x-ray crystallography. 14-3-3 proteins bound only to the phosphorylated integrin cytoplasmic peptide, with a high affinity (Kd, 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (Kd, 0.5 mM). Phosphorylation did not regulate talin binding to β2 directly, but 14-3-3 was able to outcompete talin for the binding to phosphorylated β2 integrin. X-ray crystallographic data clearly explained how phosphorylation eliminated filamin binding and induced 14-3-3 protein binding. Filamin knockdown in T cells led to an increase in stimulated cell adhesion to ICAM-1–coated surfaces. Our results suggest that the phosphorylation of β2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion.
PILAR is a novel modulator of human T-cell expansion
Authors: Huarte Eduardo , Cubillos-Ruiz Juan R. , Nesbeth Yolanda C. , Scarlett Uciane K. , Martinez Diana G. , Engle Xavier A. , Rigby William F. , Pioli Patricia A. , Guyre Paul M. , Conejo-Garcia Jose R.
Published: June 2008

Robust T-cell responses without autoimmunity are only possible through a fine balance between activating and inhibitory signals. We have identified a novel modulator of T-cell expansion named proliferation-induced lymphocyte-associated receptor (PILAR). Surface PILAR is markedly up-regulated on CD4 and, to a lesser extent, on CD8 T cells on T-cell receptor engagement. In absence of CD28 costimulation, PILAR signaling through CD161 supports CD3 antibody-dependent and antigen-specificT-cell proliferation by increasing the expression of antiapoptotic Bcl-xL and induces secretion of T helper type 1 cytokines. These effects are abrogated by PILAR blockade with specific antibodies, which decrease surface levels of CD28. In contrast, PILAR induces apoptotic death on naive and early activated T cells if CD161 engagement is blocked. PILAR is expressed by approximately 7% to 10% of CD4 T cells in 2 samples of inflammatory synovial fluid, suggesting a potential role in the pathogenesis of joint inflammation. In addition, in the ovarian cancer microenvironment, effector T cells express PILAR, but not CD161, although expression of both can be augmented ex vivo. Our results indicate that PILAR plays a central role in modulating the extent of T-cell expansion. Manipulation of PILAR signaling may be important for treatment of autoimmune diseases and cancer.
In vivo–activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease
Authors: Zhao Dongchang , Zhang Chunyan , Yi Tangsheng , Lin Chia-Lei , Todorov Ivan , Kandeel Fouad , Forman Stephen , Zeng Defu
Published: June 2008

CD103 (αEβ7) has been shown to be an excellent marker for identifying in vivo–activated FoxP3+CD4+ regulatory T (Treg) cells. It is unknown whether reinfusion of in vivo–activated donor-type CD103+ Treg cells from recipient can ameliorate ongoing chronic graft-versus-host disease (GVHD). Here, we showed that, in a chronic GVHD model of DBA/2 (H-2d) donor to BALB/c (H-2d) recipient, donor-type CD103+ Treg cells from recipients were much more potent than CD25hi natural Treg cells from donors in reversing clinical signs of GVHD and tissue damage. Furthermore, in contrast to CD25hi natural Treg cells, CD103+ Treg cells expressed high levels of CCR5 but low levels of CD62L and directly migrated to GVHD target tissues. In addition, the CD103+ Treg cells strongly suppressed donor CD4+ T-cell proliferation; they also induced apoptosis of in vivo–activated CD4+ T and B cells and significantly reduced pathogenic T and B cells in GVHD target tissues. These results indicate that CD103+ Treg cells from chronic GVHD recipients are functional, and reinfusion of the CD103+ Treg cells can shift the balance between Treg cells and pathogenic T cells in chronic GVHD recipients and ameliorate ongoing disease.
Src family tyrosine kinase Lyn mediates VWF/GPIb-IX–induced platelet activation via the cGMP signaling pathway
Authors: Yin Hong , Liu Junling , Li Zhenyu , Berndt Michael C. , Lowell Clifford A. , Du Xiaoping
Published: June 2008

The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib-IX, mediates initial platelet adhesion and transmits signals leading to platelet activation. Src family tyrosine kinases (SFKs) play an important role in VWF-induced GPIb-IX signaling. However, the SFK-dependent downstream signaling pathway is unclear but is thought to involve thromboxane A2 (TXA2) synthesis. Here we show that, although platelets deficient in SFK members, Lyn or Fyn, were defective in the TXA2-dependent second wave of platelet aggregation induced by botrocetin/VWF, only Lyn-knockout platelets were also defective in stable platelet adhesion to VWF under shear stress that is independent of the TXA2 pathway. Lyn-knockout platelets also spread poorly on VWF but spread normally on fibrinogen, indicating an important role for Lyn in VWF-mediated GPIb signaling but not in integrin outside-in signaling. Importantly, Lyn knockout abrogated VWF-induced cGMP elevation. Addition of low concentrations of 8-bromo-cGMP, however, corrected the defective stable adhesion of Lyn-knockout platelets or PP2-treated platelets on VWF. These results demonstrate an important role for Lyn in VWF/GPIb-IX–induced integrin activation mediated via the cGMP signaling pathway independently of TXA2 synthesis and also indicate that Lyn is critically important in GPIb-IX–mediated activation of the cGMP pathway.
In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1
Authors: Ahamed Jasimuddin , Burg Nathalie , Yoshinaga Keiji , Janczak Christin A. , Rifkin Daniel B. , Coller Barry S.
Published: June 2008

Transforming growth factor-β1 (TGF-β1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations. Platelets contain 40 times as much TGF-β1 as other cells and secrete it as an inactive (latent) form in complex with latency-associated peptide (LAP), which is disulfide bonded via Cys33 to latent TGF-β binding protein 1 (LTBP-1). Little is known about how latent TGF-β1 becomes activated in vivo. Here we show that TGF-β1 released from platelets or fibroblasts undergoes dramatic activation when subjected to stirring or shear forces, providing a potential mechanism for physiologic control. Thiol-disulfide exchange appears to contribute to the process based on the effects of thiol-reactive reagents and differences in thiol labeling of TGF-β1 before and after stirring or shear. Activation required the presence of LTBP, as TGF-β1 contained in complex with only LAP could not be activated by stirring when studied as either a recombinant purified protein complex or in the platelet releasates or sera of mice engineered to contain an LAP C33S mutation. Release and activation of latent TGF-β1 in vivo was demonstrated in a mouse model 5 minutes after thrombus formation. These data potentially provide a novel mechanism for in vivo activation of TGF-β1.
Polymorphic variation in surfactant protein B is associated with COPD exacerbations
Authors: Foreman M. G. , DeMeo D. L. , Hersh C. P. , Carey V. J. , Fan V. S. , Reilly J. J. , Shapiro S. D. , Silverman E. K.
Published: June 2008

Exacerbations of chronic obstructive pulmonary disease (COPD) reduce quality of life and increase mortality. Genetic variation might explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. Polymorphisms in five candidate genes, previously associated with COPD susceptibility, were analysed in order to determine whether they demonstrated association with COPD exacerbations.

A total of 88 single nucleotide polymorphisms (SNPs) in the genes microsomal epoxide hydrolase (EPHX1), transforming growth factor, beta-1 (TGFB1), serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2), glutathione S-transferase pi (GSTP1) and surfactant protein B (SFTPB) were genotyped in 389 non-Hispanic white participants in the National Emphysema Treatment Trial. Exacerbations were defined as COPD-related emergency room visits or hospitalisations using the Centers for Medicare and Medicaid Services claims data.

One or more exacerbations were experienced by 216 (56%) subjects during the study period. AnSFTPBpromoter polymorphism, rs3024791, was associated with COPD exacerbations. Logistic regression models, analysing a binary outcome of presence or absence of exacerbations, confirmed the association of rs3024791 with COPD exacerbations. Negative binomial regression models demonstrated association of multipleSFTPBSNPs (rs2118177, rs2304566, rs1130866 and rs3024791) with exacerbation rates. Polymorphisms inEPHX1,GSTP1,TGFB1andSERPINE2did not demonstrate association with COPD exacerbations.

In conclusion, genetic variation in surfactant protein B is associated with chronic obstructive pulmonary disease susceptibility and exacerbation frequency.
Shroom expression is attenuated in pulmonary arterial hypertension
Authors: Sevilla-Pérez J. , Königshoff M. , Kwapiszewska G. , Amarie O. V. , Seeger W. , Weissmann N. , Schermuly R. T. , Morty R. E. , Eickelberg O.
Published: June 2008

Shroom is a PDZ-domain protein involved in the regulation and maintenance of cytoskeletal architecture by binding to actin. Hypertrophy and altered actin organisation of pulmonary arterial smooth muscle cells (PASMC) is a hallmark of pulmonary arterial hypertension (PAH). The aim of the present study was to localise and characterise Shroom expression in the lung in experimental and idiopathic PAH (IPAH).

Shroom expression and localisation in hypoxia-induced PAH in mice and IPAH in humans,in vivo, as well as in primary PASMC,in vitro, was assessed by quantitative RT-PCR, immunofluorescence, laser-assisted microdissection and immunohistochemistry.

Shroom localised exclusively to PASMC (both bronchial and vascular) in mouse and human lungs. Bothin vivoand in primary PASMC,in vitro, Shroom exhibited spatially similar expression with α-smooth muscle actin (α-SMA). Shroom expression was significantly reduced in the mouse model of PAH, in primary murine PASMC exposed to hypoxia, and in primary PASMC isolated from patients with IPAH. The ratio between Shroom and α-SMA RNA expression further confirmed Shroom downregulation in both mouse and human PASMC.

In summary, Shroom localises exclusively to pulmonary smooth muscle cells. Shroom downregulation in pulmonary arterial hypertension suggests a link between Shroom expression and pulmonary arterial smooth muscle cell hypertrophy in pulmonary arterial hypertension.