Erythropoietin exposure of isolated pancreatic islets accelerates their revascularization after transplantation

Aims The exposure of isolated pancreatic islets to pro-angiogenic factors prior to their transplantation represents a promising strategy to accelerate the revascularization of the grafts. It has been shown that erythropoietin (EPO), a glycoprotein regulating erythropoiesis, also induces angiogenesis. Therefore, we hypothesized that EPO exposure of isolated islets improves their posttransplant revascularization. Methods Flow cytometric, immunohistochemical and quantitative real-time (qRT)-PCR analyses were performed to study the effect of EPO on the viability, cellular composition and gene expression of isolated islets. Moreover, islets expressing a mitochondrial or cytosolic H2O2 sensor were used to determine reactive oxygen species (ROS) levels. The dorsal skinfold chamber model in combination with intravital fluorescence microscopy was used to analyze the revascularization of transplanted islets. Results We found that the exposure of isolated islets to EPO (3 units/mL) for 24 h does not affect the viability and the production of ROS when compared to vehicle-treated and freshly isolated islets. However, the exposure of islets to EPO increased the number of CD31-positive cells and enhanced the gene expression of insulin and vascular endothelial growth factor (VEGF)-A. The revascularization of the EPO-cultivated islets was accelerated within the initial phase after transplantation when compared to both controls. Conclusion These findings indicate that the exposure of isolated islets to EPO may be a promising approach to improve clinical islet transplantation

Effects of aerodynamic interaction between main and tail rotors on helicopter hover performance and noise

A model test was conducted to determine the effects of aerodynamic interaction between main rotor, tail rotor, and vertical fin on helicopter performance and noise in hover out of ground effect. The experimental data were obtained from hover tests performed with a .151 scale Model 222 main rotor, tail rotor and vertical fin. Of primary interest was the effect of location of the tail rotor with respect to the main rotor. Penalties on main rotor power due to interaction with the tail rotor ranged up to 3% depending upon tail rotor location and orientation. Penalties on tail rotor power due to fin blockage alone ranged up to 10% for pusher tail rotors and up to 50% for tractor tail rotors. The main rotor wake had only a second order effect on these tail rotor/fin interactions. Design charts are presented showing the penalties on main rotor power as a function of the relative location of the tail rotor

Erythropoietin accelerates the revascularization of transplanted pancreatic islets

Background and Purpose Pancreatic islet transplantation is a promising therapeutic approach for Type 1 diabetes. A major prerequisite for the survival of grafted islets is a rapid revascularization after transplantation. Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to promote angiogenesis. Therefore, we investigated in this study whether EPO improves the revascularization of transplanted islets. Experimental Approach Islets from FVB/N mice were transplanted into dorsal skinfold chambers of recipient animals, which were daily treated with an intraperitoneal injection of EPO (500 IU·kg−1) or vehicle (control) throughout an observation period of 14 days. In a second set of experiments, animals were only pretreated with EPO over a 6‐day period prior to islet transplantation. The revascularization of the grafts was assessed by repetitive intravital fluorescence microscopy and immunohistochemistry. In addition, a streptozotocin‐induced diabetic mouse model was used to study the effect of EPO‐pretreatment on the endocrine function of the grafts. Key Results EPO treatment slightly accelerated the revascularization of the islet grafts. This effect was markedly more pronounced in EPO‐pretreated animals, resulting in significantly higher numbers of engrafted islets and an improved perfusion of endocrine tissue without affecting systemic haematocrit levels when compared with controls. Moreover, EPO‐pretreatment significantly accelerated the recovery of normoglycaemia in diabetic mice after islet transplantation. Conclusion and Implications These findings demonstrate that, particularly, short‐term EPO‐pretreatment represents a promising therapeutic approach to improve the outcome of islet transplantation, without an increased risk of thromboembolic events

Parathyroid hormone [1-34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo

SummaryObjectiveThe 1-34 amino acid segment of the parathyroid hormone (PTH [1-34]) mediates anabolic effects in chondrocytes and osteocytes. The aim of this study was to investigate whether systemic application of PTH [1-34] improves the repair of non-osteoarthritic, focal osteochondral defects in vivo.DesignStandardized cylindrical osteochondral defects were bilaterally created in the femoral trochlea of rabbits (n = 8). Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to the treatment group (n = 4) for 6 weeks, controls (n = 4) received saline. Articular cartilage repair was evaluated by macroscopic, biochemical, histological and immunohistochemical analyses. Reconstitution of the subchondral bone was assessed by micro-computed tomography. Effects of PTH [1-34] on synovial membrane, apoptosis, and expression of the PTH receptor (PTH1R) were determined.ResultsSystemic PTH [1-34] increased PTH1R expression on both, chondrocytes and osteocytes within the repair tissue. PTH [1-34] ameliorated the macro- and microscopic aspect of the cartilaginous repair tissue. It also enhanced the thickness of the subchondral bone plate and the microarchitecture of the subarticular spongiosa within the defects. No significant correlations were established between these coexistent processes. Apoptotic levels, synovial membrane, biochemical composition of the repair tissue, and type-I/II collagen immunoreactivity remained unaffected.ConclusionsPTH [1-34] emerges as a promising agent in the treatment of focal osteochondral defects as its systemic administration simultaneously stimulates articular cartilage and subchondral bone repair. Importantly, both time-dependent mechanisms of repair did not correlate significantly at this early time point and need to be followed over prolonged observation periods

Analysis of weighted networks

The connections in many networks are not merely binary entities, either present or not, but have associated weights that record their strengths relative to one another. Recent studies of networks have, by and large, steered clear of such weighted networks, which are often perceived as being harder to analyze than their unweighted counterparts. Here we point out that weighted networks can in many cases be analyzed using a simple mapping from a weighted network to an unweighted multigraph, allowing us to apply standard techniques for unweighted graphs to weighted ones as well. We give a number of examples of the method, including an algorithm for detecting community structure in weighted networks and a new and simple proof of the max-flow/min-cut theorem.Comment: 9 pages, 3 figure

Early Host Tissue Response to Different Types of Vascular Prostheses Coated with Silver Acetate or Vaporized Metallic Silver

ObjectivesIn vascular surgery, the infection of prosthetic vascular grafts represents a serious life-threatening complication. Due to the increasing resistance of hospital micro-organisms to standard antibiotic therapies, maximum effort should be put in the primary prevention of such infections. For this purpose, grafts may be coated with different antibacterial silver formulations. In the present study the different effects of silver acetate-coating and vaporized metallic silver-coating on the vascularization and perigraft inflammation during the initial phase after implantation of Intergard Silver (IS) and Silver Graft (SG) were compared.MethodsSilver acetate-coated IS and vaporized metallic silver-coated SG were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study angiogenesis and leukocyte inflammation at the implantation site by means of repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, apoptosis and cell proliferation in the newly developed granulation tissue surrounding the implants was analyzed by immunohistochemistry.ResultsIS exhibited an improved vascularization, resulting in a significantly higher functional capillary density when compared to SG. Moreover, the leukocyte inflammatory response to IS was less pronounced, as indicated by a reduced number of adherent leukocytes in perigraft venules. This was associated with a higher proliferative activity of the granulation tissue incorporating the IS when compared to SG. The numbers of apoptotic cells in the perigraft tissue were low and did not differ between the two groups.ConclusionSilver acetate-coated IS exhibits an improved vascularization and reduced perigraft inflammation during the first 14 days after implantation when compared to vaporized metallic silver-coated SG. This may contribute to reducing the risk of early perigraft seroma formation and subsequent infection

Synchronization Model for Stock Market Asymmetry

The waiting time needed for a stock market index to undergo a given percentage change in its value is found to have an up-down asymmetry, which, surprisingly, is not observed for the individual stocks composing that index. To explain this, we introduce a market model consisting of randomly fluctuating stocks that occasionally synchronize their short term draw-downs. These synchronous events are parameterized by a ``fear factor'', that reflects the occurrence of dramatic external events which affect the financial market.Comment: 4 pages, 4 figure

Shifting new media: from content to consultancy, from heterarchy to hierarchy

This is a detailed case history of one of London’s iconic new media companies, AMX Studios. Some of the changes in this firm, we assume, are not untypical for other firms in this sector. Particularly we want to draw attention to two transformations. The first change in AMX and in London’s new media industry more generally refers to the field of industrial relations. What can be observed is a shift from a rather heterarchical towards a more hierarchical organized new media industry, a shift from short-term project networks to long-term client dependency. The second change refers to new media products and services. We want to argue for a shift from cool content production towards consultancy and interactive communications solutions

(Quantum) Space-Time as a Statistical Geometry of Fuzzy Lumps and the Connection with Random Metric Spaces

We develop a kind of pregeometry consisting of a web of overlapping fuzzy lumps which interact with each other. The individual lumps are understood as certain closely entangled subgraphs (cliques) in a dynamically evolving network which, in a certain approximation, can be visualized as a time-dependent random graph. This strand of ideas is merged with another one, deriving from ideas, developed some time ago by Menger et al, that is, the concept of probabilistic- or random metric spaces, representing a natural extension of the metrical continuum into a more microscopic regime. It is our general goal to find a better adapted geometric environment for the description of microphysics. In this sense one may it also view as a dynamical randomisation of the causal-set framework developed by e.g. Sorkin et al. In doing this we incorporate, as a perhaps new aspect, various concepts from fuzzy set theory.Comment: 25 pages, Latex, no figures, some references added, some minor changes added relating to previous wor

Copyright and cultural work: an exploration

This article first discusses the contemporary debate on cultural “creativity” and the economy. Second, it considers the current state of UK copyright law and how it relates to cultural work. Third, based on empirical research on British dancers and musicians, an analysis of precarious cultural work is presented. A major focus is how those who follow their art by way of “portfolio” work handle their rights in ways that diverge significantly from the current simplistic assumptions of law and cultural policy. Our conclusions underline the distance between present top-down conceptions of what drives production in the cultural field and the actual practice of dancers and musicians