bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous administration of Ang(1-7) or A-779 does not affect the chronic hypertensive effects of angiotensin II in normal rats
Authors: Collister John P , Nahey David B
Published: April 2010

Hypothesis. The following studies were designed to test the hypothesis that simultaneous administration of either Ang(1-7) or its antagonist A-779 would affect the chronic hypertensive effects of angiotensin II (Ang II).

Introduction. Despite the well-described actions of Ang(1-7) and its role possessing opposite actions to Ang II, there have been few studies examining the role of Ang(1-7) in a chronic setting. It is well established that Ang(1-7) plays a protective role in preventing deleterious effects of Ang II in the heart, but little is known of its role in modulating the chronic hypertensive effects of Ang II.

Materials and methods. Rats were instrumented with venous catheters and telemetric pressure transducers. Arterial pressure responses were measured in rats treated with Ang II (10 ng/kg/ min) (n=9) and compared with those treated with Ang II and Ang(1-7) (24 µg/kg/h) (n=8), or the Ang(1-7) antagonist A-779 (24 µg/kg/h) (n=7) for 8 days.

Results. Mean arterial pressure rose significantly and similarly in all three groups of rats, such that by day 8 of Ang II infusion, pressures had risen 25—30 mmHg in all rats.

Conclusions. These results do not support the hypothesis that the chronic hypertensive effects of Ang II in normal rats are altered by co-administration of either Ang(1-7) or A-779.
Hypertension study in anaesthetized rabbits: protocol proposal for AT1antagonists screening
Authors: Politi Aggeliki P , Zervou Maria V , Triantafyllidi Helen , Zoumpoulakis Panagiotis G , Mavromoustakos Thomas M , Zoga Anastasia A , Moutevelis-Minakakis Panagiota , Kokotos George , Iliodromitis Efstathios K , Kremastinos Dimitris Th
Published: April 2010

Introduction: The aim of this study was to establish an optimized fast and safe protocol for the pharmacological screening of AT1antagonists.

Materials and methods : The pharmaceutical prototype AT1antagonist losartan, its active metabolite EXP3174 and the synthetic compound MMK1 were analysed in order to validate the protocol. Ang II was continuously infused while the animals received the drugs in two procedures.

Results: In the post-treatment procedure drugs were administered either in a single bolus dose or in a sequential manner. When losartan was administered in a single bolus dose, efficacy was evident until the 7th min ( p=0.012) whilst EXP3174 infusion extended the efficiency up to the end of the study ( p=0.006). In addition, the sequential injections of losartan prolonged the inhibitory time interval until the end of the study ( p=0.045). In the pre-treatment procedure, results suggested a dose-dependent inhibitory effect for both antagonists. The pressor response to Ang II was unchanged after MMK1 administration either in the post- or in the pre-treatment mode.

Conclusions: The proposed protocol appears to be safe, simple and fast for the pharmacological screening of AT1antagonists and enables the evaluation of new antagonists using lower doses than any other reported in the literature.
Augustine’s Contribution to the Republican Tradition
Authors: Cornish Paul J.
Published: April 2010

The present argument focuses on part of Augustine’s defense of Christianity in The City of God. There Augustine argues that the Christian religion did not cause the sack of Rome by the Goths in 410 CE. Augustine revised the definitions of a ‘people’ and ‘republic’ found in Cicero’s De Republica in light of the impossibility of true justice in a world corrupted by sin. If one returns these definitions to their original context, and accounts for Cicero’s own political teachings, one finds that Augustine follows Cicero’s republicanism on several key points. First, civil rule differs from mastery over slaves. Second, political life is indeterminate, so a republic could be any regime suitable for governing free human beings. Third, the prudent man may not abstain from public service. For Augustine the duty to public service is connected to his tragic portrayal of life and suffering in society after ‘the fall’. Augustine’s contribution to the republican tradition is not to be found in the concept of a natural order, but in an explanation of why that order fails.
Fascism, Marxism, and the Question of Modern Revolution
Authors: Roberts David D.
Published: April 2010

Bitterly anti-Marxist though it was, fascism now appears to have been in some sense revolutionary in its own right, but this raises new questions about the meaning of modern revolution. In a recent essay Roger Griffin, a major authority on fascism, challenges Marxists and non-Marxists to engage in a dialogue that would deepen our understanding of the relationship between the Marxist-communist and fascist revolutionary directions. Although he finds openings within the Marxist tradition, Griffin insists that, if such dialogue is to be possible, the Marxists must give up any a priori claim to the unique validity of the Marxist revolutionary project. However, Griffin’s way of framing the issues proves too limited, first because his understanding fascism as revolutionary is not rich enough, but also because he too often forces his argument to make the fascist revolution seem the archetypal 20th-century revolution. The alternative starts with a deeper understanding of the basis of the fascist claim to be spearheading, as Marxism could not, a revolutionary departure appropriate to contemporary challenges and possibilities. In asking about the commonality of the fascist and Marxist revolutions, Griffin convincingly accents a certain mode of historical consciousness that seemed to warrant a totalitarian direction. But the historical sense he draws from Walter Benjamin, and then attributes to Marxism and Leninism, misconstrues the area of commonality. Through a different way of conceiving fascism as revolutionary, and of understanding fascist-communist convergence, we can challenge the Marxists more deeply — but also suggest the basis for a more fruitful mode of dialogue around fascism, Marxism and modern revolution.
Reclaiming the Revolutionary Spirit
Authors: Smith William
Published: April 2010

This article examines Hannah Arendt’s bold and provocative proposal to institutionalize civil disobedience. First, I argue that the proposal follows from Arendt’s peculiar interpretation of this mode of protest. She sees it as an unexpected yet welcome echo of the revolutionary spirit that accompanied the foundation of the American republic. In seeking to bring civil disobedience into government, she aims to embed this spirit within the very institutional fabric of the polity. Second, I suggest that we have strong reasons to take the proposal seriously as an account of how the constitutional state should respond to dissenting minorities. The call to institutionalize civil disobedience can be defended as an approach that is different to — and ultimately more appealing than — familiar liberal and democratic perspectives on this issue.
Pascalian Ethics? Bergson, Levinas, Derrida
Authors: Vernon Richard
Published: April 2010

The ‘Pascalian’ tradition in French thought is a moral rigorism that demands practical embodiment while denying that any embodiment of its demands can ever be complete. The power of this tradition may be seen even in French political moralists of the 20th century. It is revealed in Bergson’s view that the open morality must seek practical expression through the closed society, while constantly subverting it. It is revealed in Levinas’s claim that the ‘saying’ requires to be ‘said’ but always undermines the said, so that what is explicit is ‘always wanting’. Directly, and also through the influence of Levinas, the Pascalian tradition exerts a complex influence on Derrida, in whose thoughts about the topic of justice moral rigorism transforms into an idea of radical epistemic incompleteness, or infinite deferral. ‘Pascalians’ such as Bergson, Levinas and Derrida are convinced, consequently, that the ethical can be given only sporadic or uninstitutionalized political expression; in this regard, they may be contrasted with ‘Lockeans’ who believe that political theory is at one remove from our deepest ethical or religious conclusions. In light of that contrast, the differences between Continental and Anglophone political theory may be traced to post-Reformation circumstances rather than, as is often supposed, to the Enlightenment.
Fichte’s Theory of Property
Authors: James David
Published: April 2010

I discuss J. G. Fichte’s theory of property and its implications in relation to the claim made by C. B. Macpherson that, by broadening the meaning of the term ‘property’, it becomes possible to reconcile two principles of liberal democratic theory that seem to be at odds with each other: the right to property, understood as the right to exclude others from the use or benefit of something, and the right to use and develop one’s capacities. I argue that Fichte’s broad conception of property can be viewed as an example of how this might be done. I also show, however, that Fichte demonstrates that a political reconciliation of these rights is demanded by the conceptual reconciliation of them, and that such political reconciliation may demand placing considerable limitations, in the form of state regulation and the redistribution of resources, on human freedom.
A method for assessing the visibility benefits of roadway lighting
Authors: Rea MS , Bullough JD , Zhou Y.
Published: April 2010

Photometrically accurate lighting software and a model of visual performance were used to evaluate realistic roadway lighting and driver scenarios. A great deal of data, both virtual photometric quantities and values of relative visual performance, were generated. A method for simplifying these data was developed to create practical insights about the value of different fixed roadway lighting systems. In particular, it was concluded that it is important to illuminate both high- and low-speed intersections, to provide high illumination for older drivers on high-speed roadways with intersections, and perhaps to incorporate refined photosensor-based control of lighting in highly developed areas. The approach used here enables officials responsible for public cost and public safety to make more sophisticated and rational decisions about roadway lighting.
Mindfulness and Mental Health Among African American College Students
Authors: Masuda Akihiko , Anderson Page L. , Sheehan Shawn T.
Published: April 2010

The current study examined the relation of a commonly used measure of mindfulness (Mindful Attention Awareness Scale [MAAS]) and psychological flexibility (Acceptance and Action Questionnaire [AAQ]) to mental health-related variables within an African American college sample. The study also examined these constructs as potential mediators of the link between self-concealment and mental health variables. The AAQ did not show adequate internal consistency, and thus was not used in subsequent analyses. Mindfulness was found to be a significant predictor of mental health-related variables and mediated the relation between self-concealment and emotional distress in stressful interpersonal situations (full mediation) and general psychological ill health (partial mediation). These results are suggestive that mindfulness may be useful to understand mental health within African Americans college students, although additional research is clearly needed.
Communication in Cancer Care: Discussing Complementary and Alternative Medicine
Authors: Frenkel Moshe , Ben-Arye Eran , Cohen Lorenzo
Published: April 2010

In recent years, there has been an increased interest in complementary and alternative medicine (CAM) use among people with cancer. Many are looking for informed advice and desire communication with their physicians about CAM use. Communication is crucial in establishing trust with patients, gathering information, addressing patient emotions, and assisting patients in decisions about care. The quality of communication in cancer care has been shown to affect patient satisfaction, decision making, patient distress and well-being, compliance, and even malpractice litigation. Communication is now recognized as a core clinical skill in medicine, including cancer care, and is important to the delivery of high-quality care. A communication approach that fosters a collaborative relationship that includes adequate information exchange, responds to emotional needs, and manages uncertainty can lead to informed decisions about CAM use. This type of communication can help facilitate an open discussion with cancer patients and their families about integrating CAM use into their care and help physicians fulfill their roles in caring, comforting, and healing, even when cure is not possible. In this article, the authors discuss a possible model of effective patient—physician communication about CAM use in cancer care based on a comprehensive overview of the literature.
Effects of Monascus-Fermented Rice Extract on Malignant Cell—Associated Neovascularization and Intravasation Determined Using the Chicken Embryo Chorioallantoic Membrane Model
Authors: Ho Bing-Ying , Wu Yao-Ming , Hsu Ya-Wen , Hsu Li-Chuan , Kuo Yao-Haur , Chang King-Jen , Pan Tzu-Ming
Published: April 2010

The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose- and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% ± 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy.
Correlation of Cerebral Oximetry With Internal Carotid Artery Stump Pressures in Carotid Endarterectomy
Authors: Manwaring Mark L. , Durham Christopher A. , McNally Michael M. , Agle Steven C. , Parker Frank M. , Stoner Michael C.
Published: April 2010

Objective: This study compares internal carotid artery (ICA) mean stump pressures (SPs) with cerebral oximetry monitoring during carotid endarterectomy (CEA). Methods: A total of 104 consecutive patients undergoing CEA under general anesthesia (GA) during a 10-month period were prospectively evaluated. Baseline and postcarotid clamp regional cerebral oxygen saturation (rSO2) and mean ICA SPs were measured. Demographic, surgical, and medical variables were recorded for each case. Results: There were no postoperative strokes. Thirteen patients were excluded because of incomplete data. Of the 40 patients who had <10% drop in rSO2, 6 had SP <40 mm Hg. Regional cerebral oxygen saturation with a 15% saturation drop threshold was 76.3% sensitive and 81.1% specific in detecting patients with SP <40 mm Hg. With a threshold of 20% drop, sensitivity and specificity were 57.9% and 86.8%, respectively. Conclusions: Relative drop in rSO 2 is neither sensitive nor specific in detecting patients with mean SP <40 mm Hg. These data do not support the use of cerebral oximetry as the sole monitoring modality during carotid endarterectomy under GA.
Markers of Proteolysis, Fibrinolysis, and Coagulation in Relation to Size and Growth Rate of Abdominal Aortic Aneurysms
Authors: Flondell-Sité Despina , Lindblad Bengt , Kölbel Tilo , Gottsäter Anders
Published: April 2010

We evaluated whether matrix metalloproteinases (MMPs) 2 and 9, their inhibitors, markers for fibrinolysis, and thrombin activation are associated with diameter and growth of abdominal aortic aneurysms (AAAs). Material and Methods: Matrix metalloproteinases 2 and 9, tissue inhibitor of MMPs (TIMP-1), serpine-1, tPa-serpine-1, and activated protein C— protein C inhibitor (APC-PCI) complex were analyzed in 353 patients with AAA grouped according to AAA size, and 219 gender- and age-matched healthy individuals. Follow-up of AAA growth for up to 7 years was possible in 178 of 353 patients. Results: At baseline, all groups of patients with AAA showed lower levels of MMP-2 and -9, and higher levels of TIMP-1, serpine-1, and t-Pa-serpine-1 than controls. Matrix metalloproteinase 2 correlated inversely and APC-PCI complex correlated directly with AAA diameter. We found no correlations between markers for proteolysis, fibrinolysis, coagulation, and yearly AAA growth. Conclusion: Matrix metalloproteinase 2 is lower and APC-PCI higher in patients with larger AAA, but the relevance of the markers for AAA growth is far from clarified.
Tension Hemothorax Following Endovascular Thoracic Aortic Transection Repair: Case Report
Authors: Pond Franklin , Claydon M.
Published: April 2010

Thoracic aortic transection (TAT) is the second commonest cause of death from blunt trauma surpassed only by head injury and is associated with a mortality of 80% to 90%. The injury site is typically anteromedial at the aortic isthmus where differential shear forces act during rapid deceleration. The authors report a lateral aortic laceration managed by endovascular repair that required open thoracotomy for tension hemothorax resulting from an endoleak.
Endovascular Occlusion of a Ruptured Popliteal Artery Aneurysm
Authors: Smith R. J. Paul , Gajendragadkar Parag R. , Winterbottom Andrew P. , Cooper David G. , Hayes Paul D. , Boyle Jonathan R.
Published: April 2010

Popliteal artery aneurysms are the most common of the peripheral aneurysms. Rupture is a rare complication of these aneurysms. Here we present a case of a ruptured popliteal aneurysm in a patient with severe joint disease and immobility due to rheumatoid arthritis. The condition was treated endovascularly with an Amplatzer arterial occlusion device. The aneurysm was successfully thrombosed without inducing critical limb ischemia, as the distal popliteal was chronically occluded. Ligation of peripheral aneurysms is an infrequent treatment without simultaneous bypass graft placement. Endovascular occlusion of ruptured popliteal aneurysms should be considered a valid therapeutic strategy where exclusion bypass is not required due to distal arterial occlusion.
Human Immunodeficiency Virus Postexposure Prophylaxis at Ibadan, Nigeria
Authors: Olowookere Samuel A. , Fatiregun Akinola Ayoola
Published: April 2010

HIV infection from occupational and nonoccupational exposures can be prevented through risk assessment and management with antiretroviral drug therapy (ART). This study sought to examine the pattern of presentation and outcome of clients who were given postexposure prophylaxis (PEP) at the University College Hospital, Ibadan, Nigeria. A retrospective review of case notes of clients presenting for HIV PEP from January 2005 to December 2006 was carried out. A total of 48 clients with a mean age of 27.9 ± 12.3 years underwent PEP during the period under review. Rape constituted 50% of reasons for PEP, while needle pricks and blood splash into mucous membranes constituted 25% each. Among those who received therapy, 10 (23.8%) could not complete drug therapy because of side effects. Although no client was HIV positive after the recommended 6 months of follow-up, 8 (16.7%) clients did not complete attendance to the clinic during the period.
HCV Recurrence in HIV-Infected Patients After Liver Transplant
Authors: Hughes Christopher B. , Dickson Rolland C. , Krishna Murli , Willingham Darrin L. , Satyanarayana Raj , Harnois Denise M. , Keaveny Andrew P. , Rosser Barry , Aranda-Michel Jaime , Kramer David J. , Hellinger Walter , Mendez Julio
Published: April 2010

Patients coinfected with hepatitis C virus (HCV) and HIV undergoing liver transplantation (LT) are at risk of early, aggressive HCV recurrence. This study investigates the use of frequent protocol-driven biopsies to identify HCV recurrence post LT in coinfected patients. Five consecutive HIV/HCV-coinfected patients underwent LT. Liver biopsies were obtained post LT at 1 hour; days 7, 120, and 365; then annually; and as clinically indicated. Stage 2 (Ishak) or higher fibrosis occurred in 4 of the 5 patients by 60, 120, 270, and 365 days. Two patients died of HCV recurrence and liver failure at 6 and 35 months post LT. Three patients survived more than 4 years after LT, 2 having sustained virologic responses to anti-HCV treatment. Another has histologic recurrence not responding to treatment. Hepatitis C virus recurrence can be rapid and aggressive after LT in HIV-coinfected patients. Serial biopsies identify recurrence early, allowing for prompt initiation of treatment.
We Just Can’t Seem to Do What NCLB Expects Us to Do: The Case of an Urban District Focused on NCLB Compliance
Authors: Terry Kellie
Published: April 2010

This case is situated in a Midwestern urban school district, exploring problems faced by its superintendent and administrators as they work to implement the federal No Child Left Behind Act (NCLB). Developed from a study examining the response of P-12 districts to legislative policy mandates, the case presents problems and challenges experienced by a district as it employs bureaucratic strategies to achieve NCLB-mandated outcomes. Emergent issues posed by the case study afford graduate students and educators an opportunity to use discussion questions and exercises to analyze how a P-12 district may build capacity, enabling a more effective response to educational reform mandates and student needs.
Method for Delivering a Controlled Impact to Articular Cartilage in the Rabbit Knee
Authors: Fening Stephen D. , Jones Morgan H. , Moutzouros Vasilios , Downs Brandon , Miniaci Anthony
Published: April 2010

Objective: The authors aimed to develop a mechanical model for delivering controlled impact injuries to an articular cartilage surface, with the ability to control peak contact pressure while maintaining a constant rate of loading across all impact levels. Methods: A pendulum-style impactor with a direct contact interface was fabricated, based on previously published successful models. This impactor was tested in 2 separate experiments: first with a single analog specimen and next with 15 cadaveric rabbit knee specimens. In both experiments, impacts were performed at 3 pressure levels with multiple repetitions. Peak pressure, rate of pressure application, impulse, and time to peak were evaluated. Results: There was a significant difference between each of the pressure level groups for both the analog and cadaveric experiments. There was no significant difference between the rates of pressure application for the analog specimen and a statistically significant difference only between the highest and lowest pressure level groups for the cadaveric specimen. Conclusions: Previous studies have shown that peak pressure and rate of pressure application are both significant contributors to cartilage injury. Previous models have controlled only peak contact pressure, allowing rate of loading to change as a function of peak contact pressure. This model is the first to control both variables, with a rate of pressure application that is typical of an athletic or traumatic injury in humans. Use of this model will enable researchers to investigate the isolated effects of peak pressure on progressive cartilage injuries.
Microstructure and wear properties of novel sintered cold work steel and related particle reinforced composite materials
Authors: Weber S. , Li J. R. , Theisen W.
Published: April 2010

In the field of wear resistant materials it is known, that for certain applications steel based composites produced by powder metallurgy are beneficial due to a higher wear resistance compared to conventional cast materials. Early developments of these high wear resistant MMC were dependent on hot isostatic pressing but latest experimental findings nowadays also allow for a production by liquid phase sintering. Several materials systems have already been investigated which, however, lack of a sufficient hardness in the as sintered state. Especially for wear resistant coatings it would be beneficial to avoid a separate hardening of a coated component. The low hardness in the as sintered state is related to the transformation kinetics of the metallic matrix of the coating materials, typically leading to a comparatively soft pearlitic microstructure, if the cooling rate is too low. The use of a nickel alloyed PM cold work steel as matrix material avoids this restriction, as the formation of pearlite and bainite is delayed significantly, improving the hardenability of the steel. Adding coarse hard particles of chromium carbide (Cr3C2), aluminium zirconium oxide (AlZrO) or titanium carbide (TiC) to the steel powder, composite materials with a high abrasive wear resistance can be obtained by liquid phase sintering. The development of these materials, supported by thermodynamic calculations, is presented here together with results of the microstructural investigation and wear tests.
Towards ultrahigh resolution EBSD by low accelerating voltage
Authors: Steinmetz D. R. , Zaefferer S.
Published: April 2010

By using a low SEM accelerating voltage in the range of 5–7·5 kV with an electron backscatter diffraction system, the interaction volume of electrons with matter is markedly decreased, and the spatial resolution is improved. The authors present measurements which prove this relationship. Electron backscatter diffraction at low acceleration voltage, however, is not a straightforward technique with the current equipment and a standard set-up. The authors show that an optimised working distance and dedicated sample preparation are essential to obtain improved spatial resolution for detailed nanoscale microstructure investigations.
Hematopoietic stem cell function requires 12/15-lipoxygenase–dependent fatty acid metabolism
Authors: Kinder Michelle , Wei Cong , Shelat Suresh G. , Kundu Mondira , Zhao Liang , Blair Ian A. , Puré Ellen
Published: April 2010

Fatty acid metabolism governs multiple intracellular signaling pathways in many cell types, but its role in hematopoietic stem cells (HSCs) is largely unknown. Herein, we establish a critical role for 12/15-lipoxygenase (12/15-LOX)–mediated unsaturated fatty acid metabolism in HSC function. HSCs from 12/15-LOX–deficient mice are severely compromised in their capacity to reconstitute the hematopoietic compartment in competitive and serial reconstitution assays. Furthermore, we demonstrate that 12/15-LOX is required for the maintenance of long-term HSC quiescence and number. The defect in HSCs is cell-autonomous and associated with a selective reduction in 12/15-LOX–mediated generation of bioactive lipid mediators and reactive oxygen species and with a decrease in canonical Wnt signaling as measured by nuclear β-catenin staining. These results have implications for development, aging, and transformation of the hematopoietic compartment.
Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development
Authors: Martín-Gayo Enrique , Sierra-Filardi Elena , Corbí Angel L. , Toribio María L.
Published: April 2010

The generation of natural regulatory T cells (nTregs) is crucial for the establishment of immunologic self-tolerance and the prevention of autoimmunity. Still, the origin of nTregs and the mechanisms governing their differentiation within the thymus are poorly understood, particularly in humans. It was recently shown that conventional dendritic cells (cDCs) in human thymus were capable of inducing nTreg differentiation. However, the function of plasmacytoid DCs (pDCs), the other major subset of thymic DCs, remains unknown. Here we report that pDCs resident in the human thymus, when activated with CD40 ligand (CD40L) plus interleukin-3, efficiently promoted the generation of CD4+CD25+Foxp3+ nTregs from autologous thymocytes. The progenitors of these nTregs were selectively found within CD4+CD8+ thymocytes that had accomplished positive selection, as judged by their CD69hiTCRhi phenotype. Supporting the involvement of the CD40-CD40L pathway in pDC-induced nTreg generation, we show that positively selected CD4+CD8+ progenitors specifically transcribed CD40L in vivo and up-regulated CD40L expression on T-cell receptor engagement, thereby promoting the activation of pDCs. Finally, evidence is provided that nTregs primed by pDCs displayed reciprocal interleukin-10/transforming growth factor-β cytokine expression profiles compared with nTregs primed by cDCs. This functional diversity further supports a nonredundant tolerogenic role for thymic pDCs in the human thymus.
Asthma and pulmonary arterial hypertension: do they share a key mechanism of pathogenesis?
Authors: Said S. I. , Hamidi S. A. , Gonzalez Bosc L.
Published: April 2010

Although largely distinct and seemingly unrelated, asthma and pulmonary arterial hypertension (PAH) have important pathological features in common, including inflammation, smooth muscle contraction and remodelling.

We hypothesised that these common features could be explained by one shared mechanism of pathogenesis: activation of the transcription factor NFAT (nuclear factor of activated T-cells). If this concept is validated, it could lead to the introduction of novel therapeutic strategies against both lung disorders.

In several experimental models, airway remodelling is accompanied by remodelling of smaller pulmonary arteries, validating the hypothesis of their similar pathogenesis. In addition, lungs of vasoactive intestinal peptide (VIP) knockout mice express airway hyperresponsiveness with airway inflammation and PAH with vascular remodelling, with both sets of pathological findings being reversible with VIP treatment. Preliminary data suggest that absence of the VIP gene leads to activation of the calcineurin–NFAT pathway, and that VIP is probably a physiological inhibitor of this pathway.

Enough evidence exists to support the views that asthma and PAH share important pathological features, probably related to NFAT activation, and that VIP may be a physiological modulator of this mechanism.
GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms
Authors: Jani Saurin D , Argraves Gary L , Barth Jeremy L , Argraves W Scott
Published: April 2010

Background

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases.

Results

Here we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina.

Conclusions

GeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions, overlays of genes onto KEGG pathway diagrams and heatmaps of expression intensity values. GeneMesh is freely available online at http://proteogenomics.musc.edu/genemesh/.
Initial development and structure of biofilms on microbial fuel cell anodes
Authors: Read Suzanne T , Dutta Paritam , Bond Phillip L , Keller Jürg , Rabaey Korneel
Published: April 2010

Background

Microbial fuel cells (MFCs) rely on electrochemically active bacteria to capture the chemical energy contained in organics and convert it to electrical energy. Bacteria develop biofilms on the MFC electrodes, allowing considerable conversion capacity and opportunities for extracellular electron transfer (EET). The present knowledge on EET is centred around two Gram-negative models, i.e. Shewanella and Geobacter species, as it is believed that Gram-positives cannot perform EET by themselves as the Gram-negatives can. To understand how bacteria form biofilms within MFCs and how their development, structure and viability affects electron transfer, we performed pure and co-culture experiments.

Results

Biofilm viability was maintained highest nearer the anode during closed circuit operation (current flowing), in contrast to when the anode was in open circuit (soluble electron acceptor) where viability was highest on top of the biofilm, furthest from the anode. Closed circuit anode Pseudomonas aeruginosa biofilms were considerably thinner compared to the open circuit anode (30 ± 3 μm and 42 ± 3 μm respectively), which is likely due to the higher energetic gain of soluble electron acceptors used. The two Gram-positive bacteria used only provided a fraction of current produced by the Gram-negative organisms. Power output of co-cultures Gram-positive Enterococcus faecium and either Gram-negative organisms, increased by 30-70% relative to the single cultures. Over time the co-culture biofilms segregated, in particular, Pseudomonas aeruginosa creating towers piercing through a thin, uniform layer of Enterococcus faecium. P. aeruginosa and E. faecium together generated a current of 1.8 ± 0.4 mA while alone they produced 0.9 ± 0.01 and 0.2 ± 0.05 mA respectively.

Conclusion

We postulate that this segregation may be an essential difference in strategy for electron transfer and substrate capture between the Gram-negative and the Gram-positive bacteria used here.
The independent contribution of executive functions to health related quality of life in older women
Authors: Davis Jennifer C , Marra Carlo A , Najafzadeh Mehdi , Liu-Ambrose Teresa
Published: April 2010

Background

Cognition is a multidimensional construct and to our knowledge, no previous studies have examined the independent contribution of specific domains of cognition to health related quality of life. To determine whether executive functions are independently associated with health related quality of life assessed using Quality Adjusted Life Years (QALYs) calculated from the EuroQol EQ-5D (EQ-5D) in older women after adjusting for known covariates, including global cognition. Therefore, we conducted a secondary analysis of community-dwelling older women aged 65-75 years who participated in a 12-month randomized controlled trial of resistance training. We assessed global cognition using the Mini-Mental State Examination (MMSE) and executive functions using the: 1) Stroop Test; 2) Trail Making Test (Part B) and 3) Digits Verbal Span Backwards Test. We calculated QALYs from the EQ-5D administered at baseline, 6 months and 12 months.

Results

Our multivariate linear regression model demonstrated the specific executive processes of set shifting and working memory, as measured by Trail Making Test (Part B) and Digits Verbal Span Backward Test (p < 0.01) respectively, were independently associated with QALYs after accounting for age, comorbidities, general mobility, and global cognition. The final model explained 50% of the variation in QALYs.

Conclusions

Our study highlights the specific executive processes of set shifting and working memory were independently associated with QALYs -- a measure of health related quality of life. Given that executive functions explain variability in QALYs, clinicians may need to consider assessing executive functions when measuring health related quality of life. Further, the EQ-5D may be used to track changes in health status over time and serve as a screening tool for clinicians.

Trial Registration

ClinicalTrials.gov Identifier: NCT00426881.
Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology
Authors: Paradis François W , Simard Raynald , Gaudet Daniel
Published: April 2010

Background

The availability of clinically valid biomarkers contribute to improve the diagnosis and clinical management of diseases. A valine-to-phenylalanine substitution at position 617 (V617F) in the Janus kinase 2 (JAK2) gene has been recently associated with key signaling abnormalities in the transduction of haemopoietic growth-factor receptors and is now considered as a useful clinical marker of myeloproliferative neoplasms. Several methods have recently been reported to detect the JAK2 V617F point mutation and show variable sensitivity.

Methods

Using the Luminex xMAP technology, we developed a quantitative assay to detect the JAK2V617F variant. The method was based on polymerase chain reaction (PCR) followed by hybridization to specific probes coupled with internally dyed microspheres. The assay comprises 3 steps: genomic DNA extraction, end point PCR reaction, direct hybridization of PCR fragments and quantification. It has been tested with different sources of nucleic acid.

Results

Applied to whole blood samples, this quantitative assay showed a limit of detection of 2%. A highly sensitive allele-specific primer extension reaction performed in parallel allowed to validate the results and to identify the specimens with values below 2%.

Conclusion

Direct hybridization assay using the Luminex xMAP technology allows sensitive quantification of JAK2V617F from blood spots. It is simple and can be easily performed in a clinical setting.
HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival
Authors: Younas Nizar , Wu Christine M , Shapiro Ron , McCauley Jerry , Johnston James , Tan Henkie , Basu Amit , Schaefer Heidi , Smetanka Cynthia , Winkelmayer Wolfgang C , Unruh Mark
Published: April 2010

Background

The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival.

Methods

We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival.

Results

36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models.

Conclusions

In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.
Factors associated with sex in the context of methamphetamine use in different sexual venues among HIV-positive men who have sex with men
Authors: Semple Shirley J , Strathdee Steffanie A , Zians Jim , Patterson Thomas L
Published: April 2010

Background

Harm reduction has focused primarily on reduction of high-risk substance using behaviors rather than reductions in high-risk sexual behaviors. Furthermore, most studies focus on individual behavior change, with less attention paid to the social and environmental context. This paper promotes understanding of the interplay between the individual and the social context by examining the psychosocial and behavioral characteristics of 321 methamphetamine-using HIV-positive men who have sex with men (MSM) in San Diego, CA based on the locations or venues of their sexual activities when "high" on methamphetamine.

Methods

Participants in a safer-sex intervention study underwent a baseline assessment that queried demographic and psychosocial characteristics as well as drug use and sexual risk behaviors. For purposes of analysis, respondents were classified according to their preference of sexual venue: private (e.g., home), commercial (e.g., bathhouse), or public (e.g., public park or restroom).

Results

The commercial venue group was younger, better educated, more likely to identify as gay, and significantly more likely to have used "club drugs" as compared to the other two groups. Men in the commercial- and public-venue groups reported more high-risk sex compared to the private-venue group. The public-venue group reported heavier drug and alcohol use, had significantly higher Beck depression scores, reported more experiences of stigma, and scored higher on a measure of sexual compulsivity than did the other two groups.

Conclusion

In an effort to reduce HIV/STI risk-behaviors, future studies should investigate the feasibility of modifying personal, psychosocial and structural factors associated with the use of risky sexual venues where HIV-positive methamphetamine users engage in sexual activity when "high" on methamphetamine.

Trial registration

ClinicalTrials.gov NCT00432926
Determination of silver nanoparticle release from antibacterial fabrics into artificial sweat
Authors: Kulthong Kornphimol , Srisung Sujittra , Boonpavanitchakul Kanittha , Kangwansupamonkon Wiyong , Maniratanachote Rawiwan
Published: April 2010

Silver nanoparticles have been used in numerous commercial products, including textiles, to prevent bacterial growth. Meanwhile, there is increasing concern that exposure to these nanoparticles may cause potential adverse effects on humans as well as the environment. This study determined the quantity of silver released from commercially claimed nanosilver and laboratory-prepared silver coated fabrics into various formulations of artificial sweat, each made according to AATCC, ISO and EN standards. For each fabric sample, the initial amount of silver and the antibacterial properties against the model Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria on each fabric was investigated. The results showed that silver was not detected in some commercial fabrics. Furthermore, antibacterial properties of the fabrics varied, ranging from 0% to greater than 99%. After incubation of the fabrics in artificial sweat, silver was released from the different fabrics to varying extents, ranging from 0 mg/kg to about 322 mg/kg of fabric weight. The quantity of silver released from the different fabrics was likely to be dependent on the amount of silver coating, the fabric quality and the artificial sweat formulations including its pH. This study is the unprecedented report on the release of silver nanoparticles from antibacterial fabrics into artificial sweat. This information might be useful to evaluate the potential human risk associated with the use of textiles containing silver nanoparticles.
Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram
Authors: Li Chen , Nagasaki Masao , Saito Ayumu , Miyano Satoru
Published: April 2010

Background

With an accumulation of in silico data obtained by simulating large-scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells.

Investigating the dynamic features of current computational models promises a deeper understanding of complex cellular processes. This leads us to develop a method that utilizes structural properties of the model over all simulation time steps. Further, user-friendly overviews of dynamic behaviors can be considered to provide a great help in understanding the variations of system mechanisms.

Results

We propose a novel method for constructing and analyzing a so-called active state transition diagram (ASTD) by using time-course simulation data of a high-level Petri net. Our method includes two new algorithms. The first algorithm extracts a series of subnets (called temporal subnets) reflecting biological components contributing to the dynamics, while retaining positive mathematical qualities. The second one creates an ASTD composed of unique temporal subnets. ASTD provides users with concise information allowing them to grasp and trace how a key regulatory subnet and/or a network changes with time. The applicability of our method is demonstrated by the analysis of the underlying model for circadian rhythms in Drosophila.

Conclusions

Building ASTD is a useful means to convert a hybrid model dealing with discrete, continuous and more complicated events to finite time-dependent states. Based on ASTD, various analytical approaches can be applied to obtain new insights into not only systematic mechanisms but also dynamics.