bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Quantitative Method for Identification of Failure due to Fatigue Damage
Authors: Al-Khateeb Ghazi , Shenoy Aroon
Published: August 2009

A simple quantitative method is presented which is applicable to any type of fatigue testing that uses sinusoidal strain/stress input and which will work for experimentally identifying points of failure due to fatigue damage of any kind of material being tested. The present work utilizes strain-controlled bending beam fatigue test on asphalt mixtures to demonstrate the efficacy of this method. Distortions in the hysteresis loop or waveform are tracked to pinpoint the appearance of initial microcracks and final point of complete failure due to fatigue damage. Relationship between output signals for consecutive cycles with reference to initial stable cycle is used for computing ‘R 2’. The ‘R2’ drops sharply from initial stable value of 1 to less than 0.5 and eventually to almost 0 with increasing loading cycles. The number of cycles determined from the fitted equation at ‘R2’ = 1 marks the point of first fatigue failure N fff and ‘R2’ = 0 marks the point of complete fatigue failure Ncff.
Manifestations of Power and Control: Training as the Catalyst for Scandal at the United States Air Force Academy
Authors: Callahan Jamie L.
Published: August 2009

This article explores the role of training practices at the United States Air Force Academy (USAFA) in perpetuating power and control issues and the potential consequences of those practices. This article also includes an overview of the training practices at the USAFA, issues of power and control manifested in the training process, and gendered reactions to the loss of personal control experienced during the initial socialization training.The author argues that cadet responses to control deprivation may have resulted in the (alleged) sexual assaults by male cadets and the eating disorders manifested by female cadets, both of which ultimately represent violence against women. The article concludes with implications for research and practice, including a call for recognizing the strategic role of training in forming organizational culture.
The Effect of Tax and Expenditure Limitations on Public Education Resources: A Meta-Regression Analysis
Authors: Ballal Sonali , Rubenstein Ross
Published: August 2009

While tax and expenditure limitations (TELs) are intended to restrain government taxing and spending, empirical research has arrived at different, sometimes contradictory, conclusions on their impact. In this article, we use meta-regression analysis (MRA) to sort out these differences and to draw conclusions regarding the effect of TELs on one of the largest areas of state and local spending, education. We find evidence that TELs are associated with increases in state funding for education, relative to local or combined state and local funding. The results also suggest that some methodological factors may affect study results and that study publication is associated with findings of negative TEL effects on education resources.
Licence to Think
Authors: Grey Christopher
Published: August 2009

In this reflection on the 40th volume of Management Learning I offer some thoughts about its special character. This, I suggest, consists in part in the provision of a forum for relatively unconventional work, including speculative essays. To create and sustain such a forum requires not only intellectual courage but also a willingness to confront the proliferation of ranking systems for journals, which tend to promote conformity. Given that the pressure of such systems is increasing, the ‘thought leadership’ that can come from less conventional writing is ever more difficult to sustain, and it is to the credit of the journal that it continues to provide a home for such work.
Historical Roots and Future Directions: New Challenges for Management Learning
Authors: Turnbull James Kim , Denyer David
Published: August 2009

This article explores the development of Management Learning from nascent publication for a trade association focusing on applied research to an esteemed international and learned journal. Since the mid 1970s editors and contributors have dedicated themselves to the publication of scholarly, theoretical and critical approaches. They have achieved considerable success. On the whole a much more scholarly approach has been developed in understanding management learning and has helped to legitimize it as an acceptable and appropriate field of study. Conversely there have been costs associated with this mission. We reveal a relative decline of practical, user led and collaborative research papers and contributions directly addressing the concerns of executive education and development, particularly in terms of design, delivery and evaluation. The article concludes with a plea for rigorous, scholarly contributions that are also contextual and accessible to practitioners.
Impact and Scholarship: Unlearning and Practising to Co-create Actionable Knowledge
Authors: Antonacopoulou Elena P.
Published: August 2009

This essay explores what is impact, why it matters and how it may be demonstrated through management scholarship that integrates both rigour and relevance. Attention is drawn to the importance of understanding the dynamic nature of practice and practising as critical processes that set important foundations for extending both the questions we ask and the ways in which we ask the questions that shape scholarship. A central message from this analysis is the importance of unlearning asking questions with research users so that the knowledge co-created can be actionable. The author illustrates how these issues can support management scholarship to deliver the impact it can have and highlights the importance of capturing the process of co-creating knowledge and facilitating knowledge integration as two areas for future Management and Organizational Learning scholarship. Possible avenues in which Management Learning can support the demonstration of impactful scholarship are also proposed.
Research Methods for Organizational Learning: The Transatlantic Gap
Authors: Li Shenxue , Easterby-Smith Mark , Bartunek Jean
Published: August 2009

Research design has a notable impact on the nature of management and organizational research, and there have been numerous mentions, largely anecdotal, of differences in research design between journals published in the UK and USA. This article describes a systematic study of these supposed differences through content-analysis of 295 articles about organizational learning published in eight leading British- and US-based journals over the past 20 years. The results demonstrate substantial differences in data sources, data collection, and the scale of investigations. We discuss their impact on gaps in the study o f organizational learning and o f fer our own thoughts on possible solutions (as well as challenges) for bridging these gaps.
Improvisation and Learning in Organizations— An Opportunity for Future Empirical Research
Authors: Vendelø Morten Thanning
Published: August 2009

Since the mid 1990s improvisation in organizations has attracted increasingly more attention from scholars of organizations, but in Management Learning, articles investigating learning and improvisation in organizations are absent, even if reviews of the literature on organizational improvisation suggest close links between the two concepts. Hence, there appears to be room for scholars to pursue empirical studies of connections between improvisation and learning in organizations, and thus, the purpose of this article is to provide inspiration for production and publication of such studies in Management Learning. First, the article presents a commonly accepted definition of improvisation. Thereafter, it looks at connections between improvisation and learning in organizations, and it describes recent empirical research investigating relationships between learning and improvisation in organizations. It then addresses challenges facing scholars of improvisation and learning in organization, and finally, it identifies interesting organizational contexts for empirical studies of improvisation and learning in organizations.
Coping with the Concept of Knowledge: Toward a Discursive Understanding of Knowledge
Authors: Geiger Daniel , Schreyögg Georg
Published: August 2009

The present paper is a response to a paper published by Ursula Schneider in Management Learning (Vol. 38, No.5) in which we try to clarify our position and illustrate how a discursive understanding of knowledge, as developed in our essay, can enrich the management learning debate. In building on Habermas’ theory of communicative action we suggest an understanding of knowledge which is based on intersubjective reasoning processes.
Quod erat demonstrandum? A Reaction to Geiger and Schreyögg: ‘Coping with the Concept of Knowledge: Toward a Discursive Understanding of Knowledge’
Authors: Schneider Ursula
Published: August 2009

This short essay is a reply to Geiger and Schreyögg’s reaction to the author’s article and was inspired by the editors and all authors alike. As we agree on the discursive character of (academic) knowledge, dialogue is the silver bullet to clarify meanings and thereby one’s own thinking. I thank the editors for the opportunity to respond and my colleagues for their reply (Geiger and Schreyögg, this issue). The response will be structured in three steps. First, it will delineate the ideas and concepts on which all authors seem to agree. This will be followed by the attempt to elaborate distinctly, on which concepts and/or interpretations the authors seem to disagree. In a third step some consequences of the consensus on concepts as well as on dissent for theories of knowledge and learning will be deduced.
The specificity of post-concussive symptoms in the pediatric population
Authors: Falk Ann-Charlotte , Von Wendt Lennart , Söderkvist Birgitta Klang
Published: August 2009

The study compared patterns of reported symptoms between a mild head injury group and a group of children with abdominal complaints visiting an emergency department. Children (0—15 years) admitted to an emergency department during a three-month period with a history of head injury and a comparison group of children were included. Medical records at the time of injury were reviewed and follow-up questionnaires focused on presumed symptoms related to concussion at three months post-visit. The comparison group reported significantly more change in behaviour than the head injury group. However, for the older children, higher intensity of symptoms was reported by the comparison group compared to the head injury group. Initial differences in the amount and presence of symptoms between the two groups did not reflect the findings at three months; both groups reported symptoms or changes at three months after the event. Evaluating children aged under five, their symptoms and recovery patterns after a head injury is recommended.
A self-harm training needs assessment of school nurses
Authors: Cooke Emma , James Veronica
Published: August 2009

Self-harm is acknowledged to be increasing and is especially prevalent in young people. School nurses are central to adolescent mental health, delivering initial and sustained intervention. However, few studies have considered their experiences and training needs in fulfilling this role. This training needs assessment explored the self-harm training needs of school nurses within one UK primary care trust by utilizing questionnaires and interviews developed specifically for the study. School nurses felt frustrated and inadequate when working with young people who self-harm. The majority had attended self-harm training, yet felt that it only helped a little. Nurses desired training, particularly in practical approaches when working with young people who self-harm, however, analysis suggested that they also needed underpinning theoretical knowledge. Therefore, this study highlights the need for self-harm training for school nurses, incorporating both practical approaches and theoretical knowledge, to ensure that young people who self-harm receive an effective, high-standard service.
Risk-taking behaviour in adolescence: a literature review
Authors: Leather Nicola C.
Published: August 2009

This article gives a review of the literature outlining risk-taking behaviour in the adolescent population, linking this to developmental tasks. The review includes reference to health, peers, parenting, self-esteem and quality of life issues. A theoretical overview of the research area in general is presented and links to social and society issues. The possible causes of risk-taking, including alcohol, drugs and violence, are considered and factors reviewed.
Redesigning digital dictation for physicians: A user-centred approach
Authors: Viitanen Johanna
Published: August 2009

The user-centred approach has proven its success in software and product development. However, in the healthcare domain, user-centred research methodology has been applied less widely. This article reports a study that employs a contextual inquiry method to study the prevailing dictation procedures and solutions in a hospital from the physician’s perspective. The goal was to empirically evaluate digital dictation and the other three currently used methods for making dictations, thereby eliciting information for supporting the hospital administration in their decisions concerning the further development of a dictation solution. The research indicated a number of user requirements for a dictation solution. The main conclusions were: (1) the currently used information systems need extensive improvements and redesign; (2) the observed process of digital dictation does not seem applicable for its intended context of use; (3) for future solutions, it is important to understand that the dictation user interface cannot be standardized.
Electronic software significantly improves quality of handover in a London teaching hospital
Authors: Raptis Dimitri A. , Fernandes Carl , Weiliang Chua  , Boulos Paul B.
Published: August 2009

The study compared paper-based and electronic-based medical handover with respect to quality of information transfer during hospital out-of-hours shifts, and analysed the caseload burden of the hospital night team. The participants were 1645 hospital patients transferred from the day team to the out-of-hours team over four months in 2006. Quality of information transfer was determined by clinical data handed over within pre-set fields, and caseload burden by the frequency of tasks required at handover. Handover information fields comprised patient’s demographics and location, primary diagnosis, current problem, plan of action and primary care team details. Electronic handover achieved a significantly higher number of completed fields than paper-based handover. Blood collection, checking blood and X-ray results, and adjusting fluid balance and intravenous cannulation account for most of the workload during the nightshift. Electronic handover provides better continuity of care than paper-based handover, and redistribution of tasks during working hours would benefit night staff.
How does national culture affect citizens’ rights of access to personal health information and informed consent?
Authors: Cockcroft Sophie , Sandhu Neelam , Norris Anthony
Published: August 2009

Two widely discussed and debated aspects of health law literature are ‘informed’ consent to medical treatment and the right of access to personal health information. Both are tied to the larger subject of patients’ rights, including the right to privacy. This article looks at the issue of informed consent internationally, and goes further to explain some of the inequalities across the world with respect to informed consent and patients’ rights legislation via an analysis of the take-up of key legislative attributes in patient consent. Specifically, the effect that national culture, as defined by the GLOBE variables, has on the rate and pattern of adoption of these consent elements is analysed using binary logistic regression to provide evidence of the existence or otherwise of a cultural predicate of the legislative approach. The article concludes by outlining the challenges presented by these differences.
A strategic approach to m-health
Authors: Norris A.C. , Stockdale R.S. , Sharma S.
Published: August 2009

This article proposes a strategic framework or road map for sustainable m-health. The drivers and critical success factors of this framework are identified from the literature and a survey of the views of senior strategists in the New Zealand health sector. The success factors are associated with key tasks in the framework that identify suitable applications, channel development activity, and confirm activity by continued support of innovation whilst moving successful applications into the mainstream. The two most important outcomes from the research are that m-health has a crucial, even inevitable, role to play in future healthcare, and the development and exploitation of m-health demands a top-down strategy or framework to match and encourage bottom-up innovation by healthcare practioners. Without such a strategy to guide (but not direct) innovation, many otherwise valuable advances will not be sustainable and resources will be wasted on questionable applications that will slow development and reduce credibility.
Understanding business intelligence in the context of healthcare
Authors: Mettler Tobias , Vimarlund Vivian
Published: August 2009

In today’s fast changing healthcare sector, decision makers are facing a growing demand for both clinical and administrative information in order to comply with legal and customer-specific requirements. The use of business intelligence (BI) is seen as a possible solution to this actual challenge. As the existing research about BI is primarily focused on the industrial sector, it is the aim of this contribution to translate and adapt the current findings for the healthcare context. For this purpose, different definitions of BI are examined and condensed in a framework. Furthermore, the sector-specific preconditions for the effective use and future role of BI are discussed.
Preliminary field-work: methodological reflections from northern Canadian research
Authors: Caine Ken J. , Davison Colleen M. , Stewart Emma J.
Published: August 2009

In the Canadian North researchers of all disciplines are increasingly finding that local communities are neither uninterested nor ignorant of the potential for research to benefit their communities. We propose preliminary field-work as the early stages of research in the field that allow for exploration, reflexivity, creativity, mutual exchange and interaction through the establishment of research relationships with local people often prior to the development of research protocols and ethics applications. Based on a review of field research literature combined with our own personal research narratives from northern Canadian community research, we initiate a much needed discussion on the topic of preliminary field-work in order to understand more clearly its functions and contributions. We reflect on and examine our own experiences providing methodological guidance to other researchers who are contemplating community-based field research. Preliminary fieldwork acknowledges the increasingly intertwined standards of research quality, integrity and broader research ethics.
Angiotensin II type 1 receptor gene polymorphism in myocardial infarction patients
Authors: Bhoomi Reddy Pullareddy  , Baddela Muni Venkata Srikanth Babu  , Kolla Venkata Karunakar  , Yasovanthi Jeedigunta , Potham Sampath Kumar  , Sharath Annam , Jyothy Akka
Published: August 2009

Introduction. Acute myocardial infarction is commonly known as heart attack. It is a multifactorial disease influenced by environmental and genetic factors.The objective of the present study was to investigate the association of the angiotensin II type 1 receptor gene A/C polymorphism in South Indian myocardial infarction patients.

Subjects and methods. The present study included a total number of 221 subjects (107 myocardial infarction patients and 114 age- and sex-matched controls). Demographic and clinical characteristics were collected. Lipid profiles were estimated. DNA was isolated and the angiotensin II type 1 receptor gene A/C polymorphism was determined by polymerase chain reaction.

Results. Comparison of the lipid profiles between patients and controls showed that patients had statistically highly significant values (p=0.0001).The CC genotype of the angiotensin II type 1 receptor was not associated with myocardial infarction patients when compared to controls. CC vs. AA was χ2= 2.08, odds ratio 2.30, 95% confidence interval 0.72 — 7.23, and p value was 0.14.

Conclusion. The angiotensin II type 1 receptor CC genotype is not a risk factor for myocardial infarction in patients in a South Indian population.
Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation
Authors: Tasatargil Arda , Tekcan Merih , Celik-Ozenci Ciler , Ece Gungor Nazli , Dalkiran Bedriniam
Published: August 2009

Introduction. The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could prevent endothelial dysfunction caused by aldosterone.

Methods. Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry.

Results. There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels.

Conclusion. Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration.
Four Scenes and an Epilogue
Authors: Krumer-Nevo Michal
Published: August 2009

‘Back and forth autoethnographers gaze . . . outward on social and cultural aspects of their personal experience; then ... inward, exposing a vulnerable self that is moved by and may move through, refract, and resist cultural interpretations’ (Ellis and Bochner, 2000: 739). The article presents an autoethnography in a format of four scenes and an epilogue. The scenes move from personal family memories, through memories of first professional encounters with a ‘poor’ woman client, and an encounter with volunteers from a human rights organization that fight to eradicate poverty, to an educational moment as a social work lecturer who guides her students in their search for their own way to work with people in poverty. The epilogue aims to connect the four scenes and to point at the personal, social, cultural, and political roots of a critical social work agenda regarding poverty.
A Bottom-up Definition of Self-sufficiency
Authors: Hong Philip Young P. , Sheriff Vamadu A. , Naeger Sandra R.
Published: August 2009

Self-sufficiency (SS) is the epitome of America’s ‘reluctant’ welfare state. It is generally accepted in social welfare policy circles as a concept related to independence and financial stability. Nevertheless, SS is not a term agreed upon in practice by policymakers, researchers, or service providers and is frequently used without a clear common definition. In this sense, the purpose of this study is to explore the extent to which the top-down definition of ‘economic’ SS as the social policy goal is consistent with how the clients of job training programs perceive the term. Using a grounded theory approach, a bottom-up definition of SS was derived from a focus group of low-income jobseekers. The focus group was transcribed for a content analysis from which a client-centered definition of SS was drawn. Findings suggest that SS is a process of developing psychological strength properties and a goal-oriented progression toward realistic financial outcomes. Implications for evidence-based community interventions for client empowerment and workforce development are suggested.
Engaging and Retaining Vulnerable Youth in a Short-term Longitudinal Qualitative Study
Authors: Taylor Sarah A.
Published: August 2009

This article focuses on five aspects of data collection that were effective for successfully engaging and retaining 11 vulnerable youth in a short-term longitudinal qualitative study of school and work transitions. Each youth in this study attended five meetings with the researcher over the course of three to four months, and there was no attrition. The five strategies discussed are: (1) use of self and researcher role; (2) screening procedures; (3) initial interview; (4) structure and process of participant stipends; and (5) frequency of contact. The article also reviews selected literature on retention of participants in longitudinal studies and highlights areas in which further research on engagement and retention is needed.
Visuomotor Training Improves Stroke-Related Ipsilesional Upper Extremity Impairments
Authors: Quaney Barbara M. , Jianghua He  , Timberlake George , Dodd Kevin , Carr Caitlin
Published: August 2009

Background. Unilateral middle cerebral artery infarction has been reported to impair bilateral hand grasp. Methods. Individuals (5 males and 5 females; age 33-86 years) with chronic unilateral middle cerebral artery stroke (4 right lesions and 6 left lesions) repeatedly lifted a 260-g object. Participants were then trained to lift the object using visuomotor feedback via an oscilloscope that displayed their actual grip force (GF) and a target GF, which roughly matched the physical properties of the object. Results.The subjects failed to accurately modulate the predictive GF when relying on somatosensory information from the previous lifts. Instead, for all the lifts, they programmed excessive GF equivalent to the force used for the first lift. The predictive GF was lowered for lifts following the removal of the visual feedback. The mean difference in predictive GF between the lifts before and after visual training was significant (4.35 ± 0.027 N; P ≤ .001; 95% confidence interval [CI] = 3.80-4.88). After removal of visual feedback, there was also a significant mean difference in the applied predictive GF between the “early” and “late” lifts (0.78 ± 0.029 N; P ≤ .006; 95% CI = 0.22-1.35), demonstrating continued increase in predictive GF accuracy. Conclusion. Predictive or feedforward fingertip force generation is impaired in the ipsilesional hand when lifting a novel object with precision grip. Reacquisition of the motor forces for the grasp of objects is possible after stroke. Potentially, retraining grasp control for the ipsilesional hand may translate to improved function and motor learning within the contralesional hand.
Moisture Convection Performance of External Walls and Roofs
Authors: Kalamees Targo , Kurnitski Jarek
Published: August 2009

Full-scale laboratory measurements were taken and 2D simulations were performed to determine the moisture convection performance of the joint of an external wall and an attic floor. Both the measured and simulated results showed that the building fabric is locally sensitive to exfiltration airflow as moisture convection could cause a remarkable increase in the moisture accumulation rate on the inner surface of the sheathing. The results prove that in modern houses with balanced ventilation, where the positive pressure caused by the stack effect cannot be easily controlled, it is essential to control moisture convection by good airtightness and the use of assembly solutions with improved hygrothermal performance, such as the case with mineral wool sheathing that was tested. The simulated results showed that the use of a constant moisture excess value instead of the profile did not cause any inaccuracy in the moisture content. At the same time, the use of the constant outdoor temperature over a long time period did change the hygrothermal performance, which became significantly more critical when simulated with variable outdoor temperatures. The laboratory measurement and simulation results show that in a cold climate, for the assemblies being studied with mineral wool sheathing, leakage rates of 0.1—0.2 L/(s·m) at a 10 Pa pressure difference may be used as performance criteria for moisture convection in a two-storey house with dimensioning moisture excess 4 g/m 3 and a cold outdoor climate. Previous studies on the leakage characteristics show that these leakage rates are easily achievable in practice with careful workmanship.
The functional results of post-traumatic metacarpal hand reconstruction with microvascular toe transfers
Authors: KOTKANSALO T. , VILKKI S. K. , ELO P.
Published: August 2009

The aim of this retrospective study was to evaluate the functional results of grip reconstruction after metacarpal amputation with microvascular toe transfer or transfers. The Sollerman hand function test and modified Tamai score were determined. Additionally, secondary objective outcomes were measured. As subjective outcomes, the patients were asked about pain, satisfaction, sensibility and activities of daily living (ADL). Complications and secondary operations were also recorded. An average of 12 years 5 months (range 11–270 months) follow-up of 8 patients (11 transfers) is presented. Sollerman hand function test averaged 54, range 36–73. The modified Tamai score averaged 63, range 54–70. All except one patient were either satisfied or highly satisfied. Patients’ perception of function in terms of ADL was generally good (average 26 out of 44) with many activities causing no difficulty or only slight difficulty. The study showed that it is possible to reconstruct a reasonable grip using microvascular toe transfers.
Influence of serum on the immune recognition of a synthetic lipopeptide mimetic of the 19-kDa lipoprotein from Mycobacterium tuberculosis
Authors: Schromm Andra B. , Reiling Norbert , Howe Jörg , Wiesmüller Karl-Heinz , Roessle Manfred , Brandenburg Klaus
Published: August 2009

The innate immune response provides a critical first-line defense against Mycobacterium tuberculosis, an intracellular pathogen that represents a major health threat world-wide. A synthetic lipopeptide (LP) mimicking the lipid moiety of the cell-wall associated 19-kDa lipoprotein from M. tuberculosis has recently been assigned an important role in the induction of an antibacterial immune response in host macrophages. Here, we present experimental data on the biological activities and the biophysical mechanisms underlying cell activation by synthetic 19-kDa M. tuberculosis-derived lipopeptide (Mtb-LP). Investigation of the geometry of the LP (i.e. the molecular conformation and supramolecular aggregate structure) and the preference for membrane intercalation provide an explanation for the biological activities of the mycobacterial LP. Cell activation by low concentrations of Mtb-LP was enhanced by the lipopolysaccharide—binding protein and CD14. However, surprisingly, we found that activation of human macrophages to induce pro- as well as antiinflammatory mediators (tumor necrosis factor(TNF)-α, Interleukin(IL)-6, IL-8, and IL-10) in response to the Mtb-LP is strongly reduced in the presence of serum. This observation could be confirmed for the immune response of murine macrophages which showed a strongly enhanced TNF-α release in the absence of serum, suggesting that the molecular mechanisms of immune recognition of the Mtb-LP are tailored to the ambient conditions of the lung.
Phospholipase C, p38/MAPK, and NF-κBmediated induction of MIP-3α/CCL20 by Porphyromonas gingivalis
Authors: Dommisch Henrik , Chung Whasun O. , Jepsen Søren , Hacker Beth M. , Dale Beverly A.
Published: August 2009

Macrophage inflammatory protein-3α/C-C chemokine ligand 20 (MIP-3α/CCL20) is an antimicrobial peptide that plays an important role in innate immunity. In addition to direct microbicidal effects, MIP-3α/CCL20 also exhibits cytokine-like functions that are critical during dendritic cell activation. The aim of the present study was to investigate further which signaling pathways are involved in the MIP-3α/CCL20 mRNA expression in response to whole-cell Porphyromonas gingivalis. Primary gingival epithelial cells (GECs) and the immortalized oral keratinocyte cell-line OKF6/TERT-2 were stimulated with whole-cell P. gingivalis. Prior to stimulation, GECs and OKF6/TERT-2 cells were pretreated with specific inhibitors for nuclear-factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phospholipase C (PLC), and phosphatidylinositol-3-kinase (PI3K). In GECs and OKF6/TERT-2 cells, activation of NF-κB was examined after exposure to P. gingivalis. The gene expression of MIP-3α/CCL20 was significantly induced in response to P. gingivalis (P ≤ 0.05) compared to unstimulated control cells. This induction was specifically blocked when cells were pre-incubated with inhibitors for NF-κB, MAPK, and PLC (P ≤ 0.05), but not for PI3K. These results demonstrate that P. gingivalis induces the MIP-3α/CCL20 mRNA in a NF-κB-, PLC-, and MAPKdependent manner.
A Mycobacterium avium subsp. paratuberculosis LuxR regulates cell envelope and virulence
Authors: Alonso-Hearn Marta , Eckstein Torsten M. , Sommer Sandra , Bermudez Luiz E.
Published: August 2009

Mycobacterium avium subsp. paratuberculosis adapts to the environment via the regulation of genes affecting its envelope’s composition. Bacteria grown in milk (in vivo conditions) presented differences in the cell wall-associated lipids and in the expression of genes involved in lipid metabolism (FadE8, FadE6 and MAP1420) and host cell invasion (MAP1203, LprL). A different lipid profile was also observed in the envelope of intracellular bacteria after 1 h of infection. Intracellular bacteria showed up-regulation of a LuxR regulator which controls the envelope’s composition by up-regulation of FadE8, MAP1420, MAP1203 and LprL and by down-regulation of pks12, mmpL2 and MAP2594. A LuxR-overexpressing strain with a lipid-deficient envelope phenotype, infected epithelial cells more efficiently than the wild-type bacteria; however, it was not more resistant than the wild-type strain to the action of bactericidal proteins. Here we show that LuxR regulates virulence determinants and is involved in mycobacteria adaptation to the host.
Evidence that a C1q/C1qR system regulates monocyte-derived dendritic cell differentiation at the interface of innate and acquired immunity
Authors: Hosszu Kinga K. , Santiago-Schwarz Frances , Peerschke Ellinor I.B. , Ghebrehiwet Berhane
Published: August 2009

Growing evidence shows that C1q modulates the growth and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because C1q regulates both innate and acquired immune responses, we postulated that C1q modulates the transition from monocytes to DCs, i.e. the interface between innate and acquired immunity. Human peripheral blood monocytes cultured with soluble C1q and DC growth factors (granulocyte-macrophage colony-stimulating factor + Interleukin-4) failed to down-regulate monocyte-associated (CD14, CD16) and up-regulate DCassociated (CD83, CD86) markers. Impaired DC differentiation was not due to apoptosis; further analysis revealed the development of CD14hiCD11chiCD16 +/— cells that have previously been associated with both innate and acquired immunity. Monocyte—DC precursors expressed gC1qR, the receptor for globular heads of C1q, from the outset, while cC1qR, the receptor for the collagen tails of C1q, was expressed at low levels. Notably, the binding pattern of monoclonal antibodies specific to the globular heads of C1q indicated that C1q is bound to monocytes via globular heads, presumably through gC1qR. Moreover, gC1qR levels decreased, while cC1qR levels were dramatically amplified as monocytes differentiated into immature DC. Thus, specific C1q/C1q receptor (R) interactions may control the transition from the monocyte state (innate immunity) toward the professional antigen-presenting cell state (adaptive immunity).
Lipopolysaccharide-stimulated whole blood cytokine production does not predict the inflammatory response in human endotoxemia
Authors: Dorresteijn Mirrin J. , Draisma Annelies , van der Hoeven Johannes G. , Pickkers Peter
Published: August 2009

A widely applied method to study the activation of the innate immune system is in vitro stimulation of whole blood using lipopolysaccharide (LPS). However, it is unclear if in vitro cytokine production relates to in vivo cytokine levels elicited during experimental endotoxemia or sepsis. To determine the correlation between in vitro cytokine production and the in vivo inflammatory response, blood was obtained from 15 healthy volunteers for in vitro incubation with Escherichia coli LPS, immediately followed by experimental E. coli endotoxemia. Correlations of in vitro and peak in vivo cytokine concentrations were determined using Pearson correlation coefficient. In stimulated whole blood, tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, IL-6, IL-10 and interferon (IFN)-γ were induced to 279 ± 53, 392 ± 64, 5312 ± 624, 83 ± 20 and 343 ± 85 pg/ml, respectively, whereas in vivo cytokine induction led to cytokine levels of 603 ± 123, 11 ± 1, 4999 ± 1228, 167 ± 25 and 194 ± 40 pg/ml, respectively. Correlation coefficients between the in vitro and in vivo cytokine concentrations were for TNF-α, IL-1β, IL-6, IL-10 and IFN-γ -0.10 (P = 0.7), 0.09 (P = 0.8), 0.36 (P = 0.2), 0.19 (P = 0.5) and 0.40 (P = 0.1), respectively. Comparison between in vitro and in vivo stimulation with LPS shows no correlation between the amount of cytokines produced. In vitro cytokine production, therefore, does not predict the in vivo inflammatory response.
Enhanced induction of a histamine-forming enzyme, histidine decarboxylase, in mice primed with NOD1 or NOD2 ligand in response to various Toll-like receptor agonists
Authors: Hiromi Funayama  , Ling Huang  , Yoshinobu Asada  , Yasuo Endo  , Haruhiko Takada
Published: August 2009

We investigated the immunopharmacological aspects of innate immune responses via Toll-like receptors (TLRs), NOD1 and NOD2, in terms of induction of the histamine-forming enzyme, histidine decarboxylase (HDC), activity in mice. Intravenous injection of TLR4-agonistic synthetic lipid A definitely induced HDC activity in the liver, spleen, and lungs, especially the lungs, in mice, where maximum activity was induced about 3 h after the injection of lipid A. The TLR2/6 agonistic synthetic diacyl-type lipopeptide FSL-1 and TLR3-agonistic poly I:C were also effective in inducing HDC, while the NOD2-agonistic synthetic muramyldipeptide (MDP) and NOD1-agonistic synthetic FK156 and FK565 exhibited only weak activities in this respect. Mice primed with intravenous injection of NOD1 or NOD2 agonists produced higher HDC activity following the 4—6 h later intravenous challenge with the above TLR agonists. Among the priming agents, FK565 exhibited the strongest activity, and it was effective via various administration routes — intraperitoneal, subcutaneous, intramuscular, as well as intravenous injection; furthermore, oral (gastric) administration was effective, although it needed a dose 10 times higher than that required for other administration routes. These findings suggest that HDC is induced in association with TLRs and NOD1/2, and that the newly formed histamine by the induced HDC might play important roles in the regulation of inflammatory and immune responses in various organs.
The non-peptide chemical 3,4-methylenedioxyphenol blocked lipopolysaccharide (LPS) from binding to LPS-binding protein and inhibited pro-inflammatory cytokines
Authors: Hsu Dur-Zong , Chu Pei-Yi , Liu Ming-Yie
Published: August 2009

After binding to lipopolysaccharide (LPS)-binding protein, LPS is transferred to CD14 and then to the MD2—Toll-like receptor 4 complex, which results in the progression of sepsis. We investigated how 3,4-methylenedioxyphenol (sesamol), an inexpensive natural product in sesame seeds, affects the binding of LPS and LPS-binding protein and the release of pro-inflammatory cytokines. Sesamol: (i) dose-dependently inhibited LPS from binding to LPS binding protein; (ii) significantly decreased the release of tumor necrosis factor-α and interleukin-1β in LPS-challenged peritoneal macrophages in medium and in the serum of LPS-challenged rats; and (iii) significantly reduced the mortality rate in mice given a lethal dose of LPS. We hypothesize that sesamol blocks LPS from binding to LPS-binding protein and inhibits the release of pro-inflammatory cytokines, both of which are associated with a decrease of mortality in endotoxemia.
Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes
Authors: Ciornei Cristina D. , Novikov Alexey , Beloin Christophe , Fitting Catherine , Caroff Martine , Ghigo Jean-Marc , Cavaillon Jean-Marc , Adib-Conquy Minou
Published: August 2009

To determine whether growth of bacteria in biofilms triggers a specific immune response, we compared cytokine induction in human monocytes and mouse macrophages by planktonic and biofilm bacteria. We compared Pseudomonas aeruginosa and Staphylococcus aureus, two bacteria often colonizing the airways of cystic fibrosis patients. Planktonic and biofilm S. aureus induced equivalent amounts of cytokine in human monocytes. In contrast, biofilm-forming P. aeruginosa induced a higher production of tumor necrosis factor and interleukin-6 than their planktonic counterpart, both for clinical isolates and laboratory strains. This increased cytokine production was partly dependent on phagocytosis. In contrast, no difference in cytokine induction was observed with mouse macrophages. We investigated the structures of the lipopolysaccharides (LPSs) of these Gram-negative bacteria in biofilm and planktonic cultures of P. aeruginosa. Switch between the two life-styles was shown to cause several reversible LPS structure modifications affecting the lipid A and polysaccharide moieties of both clinical isolates and laboratory strains. In addition, LPS isolated from biofilm-grown bacteria induced slightly more inflammatory cytokines than that extracted from its planktonic counterpart. Our results, therefore, show that P. aeruginosa biofilm LPS undergoes structural modifications that only partially contribute to an increased inflammatory response from human monocytes.
Monitoring of endothelial cell activation in experimental sepsis with a two-step cell culture model
Authors: Schildberger Anita , Rossmanith Eva , Weber Viktoria , Falkenhagen Dieter
Published: August 2009

The aim of this work was to establish and characterize a cell culture model for lipopolysaccharide (LPS)-induced activation of human endothelial cells. Monocytic THP-1 cells were stimulated for 4 h with 10 ng/ml LPS from Pseudomonas aeruginosa in media containing 10% human plasma. Culture supernatants containing LPS and factors secreted by THP-1 in response to stimulation were applied to human umbilical vein endothelial cells (HUVECs). Nuclear factor-κB (NF-κB) activity, expression of adhesion molecules, and cytokine secretion were quantified. In addition, the effect of adsorptive removal of tumour necrosis factor-α (TNF-α) from the THP-1 culture supernatant on HUVEC activation was assessed. After 4 h of stimulation, THP-1 cells secreted various mediators including TNF-α (854 ± 472 pg/ml), interleukin (IL)-8 (2069 ± 710 pg/ml), IL-18 (305 ± 124 pg/ml), IL-10 (14 ± 5 pg/ml), and IL-1β (24 ± 11 pg/ml). Stimulated HUVECs showed significantly increased NF-κB activity and secreted high amounts of IL-6 and IL-8. Additionally, adhesion molecules ICAM-1 and E-selectin were increased both in the culture supernatant and at the cell surface. Removal of TNF-α from the THP-1 culture supernatant prior to HUVEC stimulation resulted in a decrease in NF-κB activity, expression of adhesion molecules, as well as IL-6 secretion. The cell culture model established in this study permits the monitoring of LPS-induced endothelial activation, which plays a central role in sepsis and may serve to assess the effect of mediator modulation by methods such as extracorporeal blood purification.
Superplastic deformation of laser welded Ti–6Al–4V sheet
Authors: Cheng D. H. , Huang J. H. , Zhang H. , Zhao X. K.
Published: August 2009

Uniaxial hot tensile tests were carried out in order to investigate the superplastic deformation of laser welded Ti–6Al–4V sheet. The results revealed that the welded specimens had good superplasticity at temperature of 870–920°C and strain rate of 10−3–10−2 s−1, and the elongation was 233–397%. Dynamic globularisation was observed in the weld bead, and the acicular structure of weld bead was transforming into equiaxed grains while straining. The increasing temperature and decreasing strain rate enhanced the globularisation process.
Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome
Authors: Will Britta , Kawahara Masahiro , Luciano Julia P. , Bruns Ingmar , Parekh Samir , Erickson-Miller Connie L. , Aivado Manuel A. , Verma Amit , Steidl Ulrich
Published: August 2009

Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 μg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2-deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xenotransplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients with AML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.
GPVI: the inside story
Authors: Nurden Alan
Published: August 2009

The search is on for natural regulators of platelet reactivity. In this issue of Blood, Trifiro and colleagues confirm that the low frequency isoform of platelet GPVI (VIb) attenuates ligand-mediated signal transduction and dampens down platelet reactivity with collagen while not affecting GPVI receptor copy number.
The clot thickens (or not)
Authors: McKenzie Steven E. , Reilly Michael P.
Published: August 2009

In this issue of Blood, Gratacap and colleagues analyze the effects of the multikinase inhibitor dasatinib on platelets, helping to explain the occurrence of bleeding related to its use for CML patients resistant to or intolerant of imatinib.1 In addition, by virtue of careful experimentation using multiple functional platelet assays, these authors are paving the way for the development of kinase inhibitors as antithrombotic agents.