bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-Bundling and the Development of Hollow Clusters in the East German Chemical Industry
Authors: Bathelt Harald
Published: September 2009

After the reunification, drastic economic restructuring processes occurred in East Germany due to a double transition: the transformation of the political and economic system, and the Fordist crisis associated with ongoing globalization processes. The challenges and shifts were particularly strong in the chemical industry, which had developed a structure of mass production characterized by an unsustainable exploitation of natural and economic resources. Drawing on a conception that views transformation and restructuring as a process of regional ruptures and re-bundling, rather than one that focuses on the lock-in of old industrialized regions, this article investigates the extent to which restructuring activities have been able to generate self-sustaining regional economies and networks in the East German chemical industry.The article is based on empirical research conducted in the regions of Leuna, Schkopau and Bitterfeld-Wolfen, which provides evidence that restructuring in the chemical industry did not create fully fledged clusters with strong interfirm linkages.Although the regional economies of the East German chemical industry were well linked to West Germany and to international markets through corporate ties, networks for learning and innovation remained weak.The development of these ‘hollow clusters’ was due to the persistence of a small industry basis, the dominance of branch operations with few local ties, and the limited importance of start-up firms. Such conditions, consequently, limit the prospects for growth in the East German chemical industry, suggesting that more diversified regional policies must be developed in the future.
The Spatial Distribution of Internet Backbone Networks in Europe
Authors: Tranos Emmanouil , Gillespie Andy
Published: September 2009

This article attempts to explain the factors which determine the spatial distribution of the Internet backbone networks in Europe.These networks facilitate the modern economy by interconnecting cities, enabling communication and exchange and, consequently, enhancing the interaction between them.This infrastructural capital for the knowledge economy is far from evenly spread across Europe.The article uses principal components analysis and regression models to examine the influence of a range of socio-economic variables on the spatial distribution of the Internet backbones in Europe, and concludes that they largely follow existing patterns of development, urban concentrations of knowledge, nodes of transport provision and patterns of high accessibility.
The Why, What, and How of Reviewer Education: A Human Capital Approach
Authors: Sullivan Sherry E. , Baruch Yehuda , Schepmyer Hazlon
Published: September 2009

Reviewing has long been recognized as a critical part of the academic process of knowledge creation, development, and dissemination. However, as evidenced by recent findings from focus groups and an international survey, the relative lack of effective formal training in management PhD programs on how to review is surprising given the impact that reviewing has on the management field. Despite the importance of reviewing to the success of the management field and the careers of those in our profession, many scholars still learn how to review by the inefficient method of trial and error. In response to recent criticisms and calls for the rehabilitation of the review process, the authors discuss why doctoral students need to be educated in order to be effective reviewers, what major topics should be covered in this training, and how certain techniques can be used to educate students while also enhancing their human capital and future career success.
The Evolution of the CDM in a Post-2012 Climate Agreement
Authors: Figueres Christiana , Streck Charlotte
Published: September 2009

Despite the many calls to reform the Clean Development Mechanism (CDM), its conceptual underpinnings are strong and it will most likely survive in the post-2012 climate regime. Some modifications may be considered in the short term to strengthen the effectiveness and transparency of the mechanism without modifying the Marrakech Accords. In the medium term, substantially increased mitigation efforts in developing countries may require a combination of three possible financial mechanisms: the current activity-based CDM albeit improved, a second market mechanism that would seek to improve the long term emission trends of developing countries by promoting broad-based emission reduction programs primarily in the private sector, and a third— nonmarket—financial mechanism that would provide an incentive for the adoption of policy changes leading to a low carbon path, but where emission reductions would not be used as international offsets.
The Victim-Informed Prosecution Project: A Quasi-Experimental Test of a Collaborative Model for Cases of Intimate Partner Violence
Authors: Cattaneo Lauren Bennett , Goodman Lisa A. , Epstein Deborah , Kohn Laurie S. , Zanville Holly A.
Published: September 2009

The Victim-Informed Prosecution Project (VIP) was designed to amplify the voice of the victim in the prosecution of a battering current or ex-partner through collaboration between the prosecution and victim-centered agencies.This article describes the rationale for and design and implementation of VIP and then explores whether it increased perceived voice.While some VIP services (advocacy and civil protection order representation) were associated with increased perceived voice, the program as a whole was associated with it only in the context of greater contact with prosecutors, when cases were more likely to be felonies.We make specific recommendations for applying this model.
Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules
Authors: Kolbe Karin , Karstens Astrid , Krämer Irene
Published: September 2009

Purpose. The aim of the study was to analyze patients’ busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation.

Methods. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detection. In addition, in two patients concomitant TDM was executed. BU exposure was monitored concurrently and BU doses were targeted to achieve a steady-state plasma concentration (CSS) of 600—900 ng/mL or 900—1100 ng/mL depending on the underlying disease. In these patients blood samples were obtained 0, 60, 120, 180, 240, and 360 min after the 1st, 5th, 9th, and 13th BU dose and analyzed concurrently.

Results. For the six patients monitored retrospectively, the time to reach peak plasma BU concentration (Cmax) ranged from 1 to 5 h (mean 2.4 h). BU Cmax — values varied from 728 to 1807 ng/ mL (mean 1174 ng/mL), and BU clearance (CL/F) from 2.32 to 3.75 mL/min/kg (mean 2.97 mL/min/ kg). The mean BU steady state (CSS) concentration calculated was 973 ng/mL (range 754—1226 ng/mL) with a mean AUC of 5818 ng·h/mL (range 4521— 7171 ng·h/mL). One of the two patients receiving targeted BU doses required an upward dose adjustment. None of the eight patients suffered from vomiting during BU therapy.

Conclusions. BU active substance encapsulated without further excipients in gelatine capsules is highly suitable for oral BU therapy. However, therapeutic drug monitoring and BU dose adjustment is still advisable to achieve optimal systemic BU exposure in each individual patient.
A comparison of the rates of cisplatin (cDDP) - induced nephrotoxicity associated with sodium loading or sodium loading with forced diuresis as a preventative measure
Authors: Leu Lily , Baribeault David
Published: September 2009

Objective. To determine whether forced diuresis and sodium loading or sodium loading alone is better at preventing cisplatin-induced nephrotoxicity.

Methods. Records of 92 patients receiving cisplatin >40 mg/m2 and sodium loading with or without mannitol were reviewed to determine the incidence of nephrotoxicity, average decline in creatinine clearance, degree of nephrotoxicity, time to resolution, rates of hospitalization, and electrolyte abnormalities among patients receiving sodium loading or sodium loading with forced diuresis.

Results. The mean cisplatin dose was 64.5 mg/m2 with a majority of the subjects receiving treatment for lung cancer. The patients who received sodium loading experienced an average decline in creatinine clearance of 33.9 mL/min versus a decline of 38.9 mL/min in the group receiving forced diuresis and sodium loading (p = 0.09). Incidence of nephrotoxicity, rate of hospitalization and rates of hypokalemia or hypomagnesemia were similar between the groups. Time to resolution of nephrotoxicity was significantly different between the groups, although there were limitations in evaluating this outcome. Majority of the subjects in the sodium loading group experienced NCIC-TC Grade 0 nephrotoxicity, whereas half of the patients in the forced diuresis group experienced Grade 2 nephrotoxicity.

Conclusion. We detected no difference in the prevention of cisplatin-induced nephrotoxicity when patients were treated with sodium loading alone or with sodium loading with mannitol. No differences were detected in average decrease in creatinine clearance, incidence of nephrotoxicity, or rates of hypomagnesemia and hypokalemia. The difference in time to resolution of toxicity appeared to be significant, however there were limitations in evaluating this outcome.
Long-term stability of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bag at 4°C
Authors: Athanasopoulos Alexandre , Hecq Jean-Daniel , Vanbeckbergen Danielle , Jamart Jacques , Galanti Laurence
Published: September 2009

Objectives. Preparation of intravenous solution in advance could be efficient to improve quality assurance, security, time management, and cost saving of drug delivery. The purpose of this study was to investigate the stability of a mixture of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bags at 4°C.

Methods. The stability of five bags of solution containing 100 mg tramadol and 10 mg metoclopramide per 100 mL dextrose 5% and stored at 4°C was studied during 32 days and concentrations measured by high performance liquid chromatography-diode array detection.

Results. No degradation interference nor modification in retention times were observed throughout the study period. At day 32, tramadol concentration was 96.9% ± 2.1 and metoclopramide 97.2% ± 1.3 of the initial concentration.

Conclusion. Based on a shelf-life of 90% residual potency, tramadol and metoclopramide were compatible and stable for at least 32 days at 4°C and can be prepared in advance in a centralized intravenous additive service facility. J Oncol Pharm Practice (2009) 15: 195—200.
What if it Didn’t All Begin and End with Containment? Toward a Leaky Sense of Self
Authors: Manning Erin
Published: September 2009

In Esther Bick’s psychoanalytic theory, the infant’s relation to the world is mediated by the skin’s capacity to serve as a container for experience. As the infant develops, containment increasingly expresses cohesion of self, as fostered by the continued interaction with the caretaker. Through an emphasis on particular forms of interaction — forms that specifically involve skin-to-skin touch — an infant is given the receptacle necessary for eventual interactive self-sufficiency. But what if the skin were not a container? What if the skin were not a limit at which self begins and ends? What if the skin were a porous, topological surfacing of myriad potential strata that field the relation between different milieus, each of them a multiplicity of insides and outsides? This article explores these questions through Daniel Stern’s account of infancy.
Skin and the Self: Cultural Theory and Anglo-American Psychoanalysis
Authors: Lafrance Marc
Published: September 2009

In recent years, a number of cultural theorists have made important contributions to the study of the body’s surface. Despite their importance, however, none of these contributions provides us with a systematic framework for understanding why the body’s surface — its skin — matters to the extent that it does. In this article, I seek to provide such a framework and, in doing so, to shed light on why the skin and the self seem to share a special and sometimes strained relationship. To this end, I will present a critical introduction to the work of two contemporary Anglo-American psychoanalysts: Esther Bick and Thomas Ogden. Throughout this introduction, I will show how both Bick and Ogden — despite the fact that they are almost completely unknown outside clinical circles — offer up a host of conceptual tools that could prove useful to cultural theorists interested in making sense of the relationship between the skin and the self.
Jurus, Jazz Riffs and the Constitution of a National Martial Art in Indonesia
Authors: Wilson Lee
Published: September 2009

Pencak Silat is a martial art, performance practice and system of body cultivation prevalent throughout much of Indonesia and the Malay-speaking world. This article compares different modalities of the practice and pedagogy of Sundanese Pencak Silat in West Java with more recent attempts to standardize practice at a national level under the auspices of the Indonesian Pencak Silat Association ( Ikatan Pencak Silat Indonesia). Drawing on David Sudnow’s seminal account of learning how to play jazz piano, it is suggested that learning how to improvise is a highly structured process that proceeds from the mastery of certain generic principles from which are generated potentially unbounded repertoires of habitual response. In the institutionalized instruction that is propagated by IPSI generative potential is subjugated to the desire to achieve homogeneity in practice. Aspects of Pencak Silat as it is taught nationally under the auspices of IPSI are examined in relation to the notion of spectacle. In conclusion, it is argued that the limits of the Nationalist project become self-evident as the dynamic potential of the body in Sundanese Pencak Silat is subsumed in an attempt to achieve fixity of the symbolic order.
Adapter proteins and promoter regulation of the angiotensin AT2 receptor — implications for cardiac pathophysiology
Authors: Funke-Kaiser Heiko , Reinemund Jana , Steckelings Ulrike M , Unger Thomas
Published: September 2009

The angiotensin AT2receptor (AT2R) represents an important component of the renin-angiotensin system since it is involved in the (patho) physiology of different cardiovascular and neuronal diseases. Furthermore, AT2receptors can partly mediate beneficial effects of angiotensin AT1receptor (AT1R) blockers, and direct pharmacological AT2receptor agonism emerges as a novel therapeutic strategy. This review discusses the constitutive and ligand-mediated activity as well as the signal transduction of the AT2receptor, focusing on adapter proteins which directly bind to this receptor. Direct protein-protein interaction partners of the AT2receptor described so far include the transcription factor promyelocytic zinc finger protein, AT2receptor binding protein and the AT1receptor. In addition, the putative crosstalk of the AT2receptor with the renin/ prorenin receptor (RER) via the promyelocytic zinc finger protein (PLZF) and the role of oestrogens on the regulation of the AT2receptor are presented. Conceiving the coupling of the AT2receptor to different adapter proteins with distinct and partly opposing cellular effects and the implications of its constitutive activity might help to overcome the current controversies on the (patho)physiological role of the AT2receptor.
Developing a practice-theory model in pre-service teacher education in Greece
Authors: Tsafos Vassilis
Published: September 2009

This paper deals with the use of action research in a postgraduate teacher education programme. The first part of the article presents the initial education of secondary teachers in Greece, as well as a postgraduate university programme that could be viewed as an alternative pre-service teacher education (PTE) programme, as implemented in a partnership between a tertiary education institution and certain secondary schools. The second part of the article describes the research I conducted during the programme, as an educator and researcher. It is a case study, aiming at investigating how the school-based PTE programme was experienced by its participants, including the student-teachers and myself, as their supervisor and an educator from a tertiary education institution. Data were collected from questionnaire surveys and interviews administered to the student-teachers, as well as from my personal journal.
New action research techniques
Authors: Quinlan Elizabeth
Published: September 2009

The use of various creative art forms in the research process is reflective of the turn towards interpretative practices that make visible certain aspects of the social world. Theatre, especially, has the capacity to convey meanings that pertain to the flux of social relationships. Reported in this paper is a particular use of theatre that is located in a history and tradition of liberatory social action. In Participatory Theatre, performative enactments are used to investigate the social arrangements that impede progressive change. Participatory Theatre opens up productive spaces for reflexivity and creates knowledge that is grounded in immediate experience and direct experiment. It is accomplished through an iterative process that involves action, reflection and action. In this article the use of Participatory Theatre in an action research project is described for the purposes of establishing its legitimacy as a viable action research technique. The project was motivated and sustained by the needs of a group of health care workers in a western Canadian province to address the problem of workplace bullying. The project confirms that envisioning alternative solutions to the problem of workplace bullying need not be derived in schools of management science; these can come from those on the ‘shop-floor’.
Constructing transnational action research networks
Authors: Brown L. David , Gaventa John
Published: September 2009

This article examines the construction of transnational action research networks that bridge local and global, practice and research, North and South, and many disciplines. Using an ‘insider—outsider’ approach the article examines the emergence of the Development Research Centre on Citizenship, Participation and Accountability as a network of partners from seven countries concerned with research, capacity building and policy influence. The article examines how this network constructed shared goals and values, developed relationships and trust, and created network architectures to support action research, policy influence and capacity building. It also explores implications of the network’s evolution for change processes, bridging leadership, mutual accountability and institutional embeddedness.
Multi-site action research
Authors: Fuller-Rowell Thomas E.
Published: September 2009

Classical action research within single organizations has become a well established and differentiated approach since its inception more than six decades ago. More recently, many have built on the foundational principles of action research to develop and implement larger-scale, multi-organization, action research approaches. Multi-organization action research has largely taken the form of coalition-based processes, where diverse stake-holders have come together to explore issues of mutual concern through a centralized action research process. Less frequently, multi-organization initiatives have implemented distinct action research processes, in a coordinated manner, within each of several involved organizations. This article refers to the later variety as multi-site action research (MSAR). Building on previous work, a conceptual framework for MSAR is developed.
What kind of respect is this?
Authors: Wood Lesley A.
Published: September 2009

In this article I attempt to answer the question, ‘How can I influence teachers to be able to contribute to changing social/cultural norms and practices that hamper effective HIV & AIDS education and prevention?’ There is a growing realization that HIV & AIDS education and prevention initiatives need to move away from trying to change the sexual behaviour of individuals towards addressing societal and cultural factors which promote rapid transmission of the virus. However, societal and cultural change has to start with helping individuals to imagine alternative ways of thinking and being. Teachers occupy a powerful position when it comes to changing mindsets and challenging norms, but they themselves have been shaped and influenced by their culture and may not, therefore, ‘see’ the need to question prevailing norms, and/or may be so constrained by these social and cultural forces that they are unable to do so. Following a values-based action research approach, I describe how I adopted emancipatory pedagogies in an attempt to influence teachers to develop their own theories of practice with regard to HIV & AIDS prevention and education in their specific cultures. As validation of my claims to having contributed to the development of educational theories about HIV & AIDS prevention and education, I invite the reader to evaluate my narrative against specific criteria. I also present my educational value of respect as a living standard of judgement.
Anti-inflammatory effects of simvastatin on adipokines in type 2 diabetic patients with carotid atherosclerosis
Authors: Hu Yun , Tong Guoyu , Xu Wei , Pan Jiajia , Ryan Kathy , Yang Rongze , Shuldiner Alan R. , Gong Da-Wei , Zhu Dalong
Published: September 2009

Objective: Statins are extensively used for lowering LDL-cholesterol and reducing cardiovascular events. Recent studies have shown that statins have beneficial anti-inflammatory effects. We aimed to determine whether and how adipokines are regulated during statin treatment in type 2 diabetic patients.

Method: In this study,we investigated the changes of CRP and inflammation-related adipokines (SAA,IL-6,TNFα and adiponectin) in 23 type 2 diabetic patients with atherosclerosis who received statin therapy, and 20 diabetic patients with atherosclerosis and 14 diabetic patients without atherosclerosis who did not receive statin therapy for a period of three months.

Results: By the end of the simvastatin treatment (40 mg, daily), LDL-cholesterol was decreased by 16.7% and HDL-cholesterol was increased by 31.9%. SAA, CRP, TNFα and IL-6 levels were decreased by 31.8%, 66.2%, 53.9% and 14%, respectively and adiponectin was increased by 59.6%, compared with the baseline levels. Interestingly, the decrease of SAA was positively correlated with that of LDL-cholesterol but negatively with HDL-cholesterol during statin treatment. Among the adipokines, the decrease of SAA was positively correlated with TNFα ( r = 0.50, p = 0.016).

Conclusion: The results suggest that adipokines may be differentially regulated and independent of cholesterol changes and that adipokines may be a mediator, and the adipose tissue may be a target of statins’ anti-inflammatory effect.
Dielectric properties in GHz range of porous Si3N4–BN–SiO2 ceramics with considerable flexural strength prepared by low temperature sintering in air
Authors: Han J. C. , Sun Y. B. , Zhang Y. M.
Published: September 2009

Porous Si3N4–BN–SiO2 ceramics with ultimate apparent porosities between 0·140 and 0·799 were fabricated in air at 1100°C by partial sintering using core starch as both consolidator and pore former in the green bodies. The pores were derived from burning off the starch, the partial oxidation of silicon nitride and the stack of particles of the start materials. Effect of retaining time on the microstructure of sintering bodies was analysed by SEM analysis. Reference intensity ratio (RIR) technique based on the X-ray diffractometry results demonstrated the phase components content of sintered bodies. Influence of porosity on the flexural strength of porous Si3N4–BN–SiO2 ceramics was investigated. The ceramic with a porosity of 0·140 attained a maximal flexural strength of 60±4·11 MPa. In addition, the dielectric constants and loss tangents were presented for porous Si3N4–BN–SiO2 triphase ceramics in the frequency range of 18–40 GHz, and the real part of dielectric constant of the materials reached as low as 2·67 at the porosity of 0·732 at a frequency of 20 GHz.
Effect of Bi2O3 coating of whisker on thermal expansion behaviour of aluminium composite reinforced by aluminium borate whisker
Authors: Li Z. J. , Fei W. D. , Wang L. D. , Liu L. M.
Published: September 2009

The thermal expansion behaviours of aluminium composites reinforced by ABOw with and without Bi2O3 coating are studied. The results show that the coating could influence the thermal expansion behaviour of composite. The coefficient of thermal expansion (CTE) of the composite with Bi2O3 coating is higher than that of the composite without coating. In addition, the heat treatment influences the thermal expansion behaviours of composite with Bi2O3 coating. The CTEs of the heat treatment composites are lower compared to as cast composite. At the same time, the quenching can boost the CTE of the composite compared with the annealing.
The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling
Authors: Szczur Kathleen , Zheng Yi , Filippi Marie-Dominique
Published: September 2009

Neutrophil migration to sites of infection is the first line of cellular defense. A key event of migration is the maintenance of a polarized morphology, which is characterized by a single leading edge of filamentous actin and a contractile uropod devoid of filamentous actin protrusions. Using a mouse model of high Cdc42 activity, we previously demonstrated the importance of Cdc42 activity in neutrophil migration. However, the specific functions of Cdc42 in this process remain to be understood. Using neutrophils genetically deficient in Cdc42, we show that Cdc42 regulates directed migration by maintaining neutrophil polarity. Although it is known to be activated at the front, Cdc42 suppresses protrusions at the uropod. Interestingly, Cdc42 makes use of the integrin CD11b during this process. Cdc42 determines the redistribution of CD11b at the uropod. In turn, using CD11b-null cells and CD11b crosslinking experiments, we show that CD11b modulates myosin light chain phosphorylation to suppress lateral protrusions. Our results uncover a new mechanism in which Cdc42 regulates the uropod through CD11b signaling to maintain polarity in migrating neutrophils. It also reveals new functions for CD11b in neutrophil polarity.
The therapeutic effect of bone marrow–derived liver cells in the phenotypic correction of murine hemophilia A
Authors: Yadav Neelam , Kanjirakkuzhiyil Sumod , Kumar Suresh , Jain Manish , Halder Ashutosh , Saxena Renu , Mukhopadhyay Asok
Published: September 2009

The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created enormous interest in applying this process to the development of cellular medicine for degenerative and genetic diseases. Because the liver is the primary site of factor VIII (FVIII) synthesis, we hypothesized that the partial replacement of mutated liver cells by healthy cells in hemophilia A mice could manage the severity of the bleeding disorder. We perturbed the host liver with acetaminophen to facilitate the engraftment and hepatic differentiation of lineage-depleted enhanced green fluorescent protein-expressing BMCs. Immunohistochemistry experiments with the liver tissue showed that the donor-derived cells expressed the markers of both hepatocytes (albumin and cytokeratin-18) and endothelial cells (von Willebrand factor). The results of fluorescent in situ hybridization and immunocytochemistry experiments suggested that differentiation was direct in this model. The BMC-recipient mice expressed FVIII protein and survived in a tail clip challenge experiment. Furthermore, a coagulation assay confirmed that the plasma FVIII activity was maintained at 20.4% (± 3.6%) of normal pooled plasma activity for more than a year without forming its inhibitor. Overall, this report demonstrated that BMCs rescued the bleeding phenotype in hemophilia A mice, suggesting a potential therapy for this and other related disorders.
2D proteome analysis initiates new Insights on the SalmonellaTyphimurium LuxS protein
Authors: Kint Gwendoline , Sonck Kathleen AJ , Schoofs Geert , De Coster David , Vanderleyden Jos , De Keersmaecker Sigrid CJ
Published: September 2009

Background

Quorum sensing is a term describing a bacterial communication system mediated by the production and recognition of small signaling molecules. The LuxS enzyme, catalyzing the synthesis of AI-2, is conserved in a wide diversity of bacteria. AI-2 has therefore been suggested as an interspecies quorum sensing signal. To investigate the role of endogenous AI-2 in protein expression of the Gram-negative pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), we performed a 2D-DIGE proteomics experiment comparing total protein extract of wildtype S. Typhimurium with that of a luxS mutant, unable to produce AI-2.

Results

Differential proteome analysis of wildtype S. Typhimurium versus a luxS mutant revealed relatively few changes beyond the known effect on phase 2 flagellin. However, two highly differentially expressed protein spots with similar molecular weight but differing isoelectric point, were identified as LuxS whereas the S. Typhimurium genome contains only one luxS gene. This observation was further explored and we show that the S. Typhimurium LuxS protein can undergo posttranslational modification at a catalytic cysteine residue. Additionally, by constructing LuxS-βla and LuxS-PhoA fusion proteins, we demonstrate that S. Typhimurium LuxS can substitute the cognate signal peptide sequences of β-lactamase and alkaline phosphatase for translocation across the cytoplasmic membrane in S. Typhimurium. This was further confirmed by fractionation of S. Typhimurium protein extracts, followed by Western blot analysis.

Conclusion

2D-DIGE analysis of a luxS mutant vs. wildtype Salmonella Typhimurium did not reveal new insights into the role of AI-2/LuxS in Salmonella as only a small amount of proteins were differentially expressed. However, subsequent in depth analysis of the LuxS protein itself revealed two interesting features: posttranslational modification and potential translocation across the cytoplasmic membrane. As the S. Typhimurium LuxS protein does not contain obvious signal motifs, it is speculated that LuxS is a new member of so called moonlighting proteins. These observations might have consequences in future studies on AI-2 quorum signaling in S. Typhimurium.
Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study
Authors: Wolf Christiane , Gramer Eugen , Müller-Myhsok Bertram , Pasutto Francesca , Reinthal Eva , Wissinger Bernd , Weisschuh Nicole
Published: September 2009

Background

Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.

Methods

Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.

Results

Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.

Conclusion

Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.
The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey
Authors: Tan Hern Tze , Rahman Rosliza Abdul , Gan Siew Hua , Halim Ahmad Sukari , Hassan Siti Asma' , Sulaiman Siti Amrah , BS Kirnpal-Kaur
Published: September 2009

Background

Antibiotic resistance of bacteria is on the rise, thus the discovery of alternative therapeutic agents is urgently needed. Honey possesses therapeutic potential, including wound healing properties and antimicrobial activity. Although the antimicrobial activity of honey has been effectively established against an extensive spectrum of microorganisms, it differs depending on the type of honey. To date, no extensive studies of the antibacterial properties of tualang (Koompassia excelsa) honey on wound and enteric microorganisms have been conducted. The objectives of this study were to conduct such studies and to compare the antibacterial activity of tualang honey with that of manuka honey.

Methods

Using a broth dilution method, the antibacterial activity of tualang honey against 13 wound and enteric microorganisms was determined; manuka honey was used as the control. Different concentrations of honey [6.25-25% (w/v)] were tested against each type of microorganism. Briefly, two-fold dilutions of honey solutions were tested to determine the minimum inhibitory concentration (MIC) against each type of microorganism, followed by more assays within a narrower dilution range to obtain more precise MIC values. MICs were determined by both visual inspection and spectrophotometric assay at 620 nm. Minimum bactericidal concentration (MBC) also was determined by culturing on blood agar plates.

Results

By visual inspection, the MICs of tualang honey ranged from 8.75% to 25% compared to manuka honey (8.75-20%). Spectrophotometric readings of at least 95% inhibition yielded MIC values ranging between 10% and 25% for both types of honey. The lowest MBC for tualang honey was 20%, whereas that for manuka honey was 11.25% for the microorganisms tested. The lowest MIC value (8.75%) for both types of honey was against Stenotrophomonas maltophilia. Tualang honey had a lower MIC (11.25%) against Acinetobacter baumannii compared to manuka honey (12.5%).

Conclusion

Tualang honey exhibited variable activities against different microorganisms, but they were within the same range as those for manuka honey. This result suggests that tualang honey could potentially be used as an alternative therapeutic agent against certain microorganisms, particularly A. baumannii and S. maltophilia.
Identifying research priorities for health care priority setting: a collaborative effort between managers and researchers
Authors: Smith Neale , Mitton Craig , Peacock Stuart , Cornelissen Evelyn , MacLeod Stuart
Published: September 2009

Background

To date there has been relatively little published about how research priorities are set, and even less about methods by which decision-makers can be engaged in defining a relevant and appropriate research agenda. We report on a recent effort in British Columbia to have researchers and decision-makers jointly establish an agenda for future research into questions of resource allocation.

Methods

The researchers enlisted decision-maker partners from each of British Columbia's six health authorities. Three forums were held, at which researchers and decision-makers from various levels in the health authorities considered possible research areas related to three key focus areas: (1) generation and use of decision criteria and measurement of 'benefit' against such criteria; (2) identification of so-called 'disinvestment' opportunities; and (3) evaluation of the effectiveness of priority setting procedures. Detailed notes were taken from each forum and synthesized into a set of qualitative themes.

Results

Forum participants suggested that future research into healthcare priority setting would benefit from studies that were longitudinal, comparative, and/or interdisciplinary. As well, participants identified two broad theme areas in which specific research projects were deemed desirable. First, future research might usefully consider how formal priority setting and resource allocation projects are situated within a larger organizational and political context. Second, additional research efforts should be devoted to better understanding and improving the actual implementation of priority setting frameworks, particularly with respect to issues of change management and the resolution of impediments to action on recommendations for resource allocation.

Conclusion

We were able to validate the importance of initial areas posed to the group and observed emergence of additional concerns and directions of critical importance to these decision-makers at this time. It is likely that the results are broadly applicable to other healthcare contexts. The implementation of this research agenda in British Columbia will depend upon the ability of the researchers and decision-makers to develop particular projects that fit within the constraints of existing funding opportunities. The process of engagement itself had benefits in terms of connecting decision-makers with their peers and sparking increased interest in the use and refinement of priority setting frameworks.
The axonal repellent, Slit2, inhibits directional migration of circulating neutrophils
Authors: Tole Soumitra , Mukovozov Ilya M , Huang Yi-Wei , Magalhaes Marco A O , Yan Ming , Crow Min Rui , Liu Guang Ying , Sun Chun Xiang , Durocher Yves , Glogauer Michael , Robinson Lisa A
Published: September 2009

Slit2, a potentially powerful anti-inflammatory agent, inhibits polarization and chemotaxis, but not random movement, of primary neutrophils towards diverse chemoattractants, in vitro and in vivo.

In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals are provided by many different chemotactic molecules, such that blockade of one may not prevent neutrophil recruitment effectively. The Slit family of secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows that by inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit migration of other cell types toward a variety of chemotactic factors in vitro and in vivo. The role of Slit2 in inflammation, however, has been largely unexplored. We isolated primary neutrophils from human peripheral blood and mouse bone marrow and detected Robo-1 expression. Using video-microscopic live cell tracking, we found that Slit2 selectively impaired directional migration but not random movement of neutrophils toward fMLP. Slit2 also inhibited neutrophil migration toward other chemoattractants, namely C5a and IL-8. Slit2 inhibited neutrophil chemotaxis by preventing chemoattractant-induced actin barbed end formation and cell polarization. Slit2 mediated these effects by suppressing inducible activation of Cdc42 and Rac2 but did not impair activation of other major kinase pathways involved in neutrophil migration. We further tested the effects of Slit2 in vivo using mouse models of peritoneal inflammation induced by sodium periodate, C5a, and MIP-2. In all instances, Slit2 reduced neutrophil recruitment effectively (P<0.01). Collectively, these data demonstrate that Slit2 potently inhibits chemotaxis but not random motion of circulating neutrophils and point to Slit2 as a potential new therapeutic for preventing localized inflammation.
Sonographic and Electrodiagnostic Evaluations in Patients With Aromatase Inhibitor–Related Arthralgia
Authors: Dizdar Omer , Özçakar Levent , Malas Fevziye Ünsal , Harputluoglu Hakan , Bulut Nilufer , Aksoy Sercan , Ozisik Yavuz , Altundag Kadri
Published: September 2009

Purpose

To investigate the prevalence of arthralgia in breast cancer patients taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment including autoimmune serology, musculoskeletal sonography, and electromyography (EMG) in these patients.

Patients and Methods

Postmenopausal patients with stage I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92). Patients who were not receiving hormone treatment were included as a control group (n = 28). Musculoskeletal sonography and EMG were applied to the patients and the controls along with markers of autoimmunity.

Results

Thirty patients (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most commonly affected joints were knee (70%), wrist (70%), and small joints of the hand (63%). Patients taking AIs had increased tendon thicknesses compared with those who never received AIs (P < .001). Patients with AI-related arthralgia had higher rates of effusion in hand joints/tendons than those without arthralgia (P = .033). More patients with AI-related arthralgia had EMG findings consistent with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No significant difference was observed in erythrocyte sedimentation rates, C-reactive protein, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, or anticyclic citrullinated peptide levels between patients and controls or between those with and without arthralgia.

Conclusion

Patients with AI-related arthralgia often show tenosynovial changes suggesting tenosynovitis, exerting local problems but lacking a systemic inflammatory component. Our finding of increased CTS frequency also supports this hypothesis.
Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034
Authors: Chadburn Amy , Chiu April , Lee Jeannette Y. , Chen Xia , Hyjek Elizabeth , Banham Alison H. , Noy Ariela , Kaplan Lawrence D. , Sparano Joseph A. , Bhatia Kishor , Cesarman Ethel
Published: September 2009

Purpose

Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis.

Patients and Methods

We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts.

Results

The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL.

Conclusion

These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.
Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897
Authors: Ambrosone Christine B. , Barlow William E. , Reynolds Wanda , Livingston Robert B. , Yeh I-Tien , Choi Ji-Yeob , Davis Warren , Rae James M. , Tang Li , Hutchins Laura R. , Ravdin Peter M. , Martino Silvana , Osborne C. Kent , Lyss Alan P. , Hayes Daniel F. , Albain Kathy S.
Published: September 2009

Purpose

Myeloperoxidase (MPO) generates reactive oxygen species and also activates xenobiotics . In a rigorous clinical trial (Southwest Oncology Group SWOG-8897), we examined relationships between genotypes and disease-free survival (DFS) among women treated for breast cancer, as well as those who did not receive adjuvant chemotherapy.

Patients and Methods

Patients were assigned to risk groups according to standard prognostic features; the low-risk group (n = 753 genotyped) received follow-up only, and the high-risk group (n = 401 genotyped) was randomly assigned to adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or cyclophosphamide, doxorubicin, and fluorouracil (CAF), with or without tamoxifen. DNA from archived normal lymph node tissue was genotyped, and Cox proportional hazard models were used to calculate DFS associated with MPO genotypes.

Results

Among women in the treatment arm, those with MPO G alleles had more than a two-fold reduction in hazard of recurrence (adjusted hazard ratio [HR] for GA genotypes, 0.51; 95% CI, 0.21 to 0.99; HR for GG genotypes, 0.41; 95% CI, 0.21 to 0.77). Effects were greatest among women who were further randomly assigned to tamoxifen (HR for GA genotypes, 0.28; 95% CI, 0.12 to 0.69; HR for GG genotypes, 0.19; 95% CI, 0.08 to 0.45). There were no significant associations between genotypes and DFS among women in the untreated arm, and relationships between genotypes and DFS did not differ by CAF or CMF.

Conclusion

These results, observed in two independent study populations, indicate that high-activity MPO genotypes are associated with better survival among women receiving cyclophosphamide-containing therapy, particularly when followed by tamoxifen therapy. MPO can be inhibited and/or upregulated by commonly used drugs; thus, our findings merit further investigation for optimization of therapeutics for breast cancer.