Publication of original research in urologic journals - a neglected orphan?

The pathophysiologic mechanisms behind urologic disease are increasingly being elucidated. The object of this investigation was to evaluate the publication policies of urologic journals during a period of progressively better understanding and management of urologic disease. Based on the ISI Web of Knowledge Journal Citation Reports and the PubMed database, the number and percentage of original experimental, original clinical, review or commentarial articles published between 2002–2010 in six leading urologic journals were analyzed. “British Journal of Urology International”, “European Urology”, “Urologic Oncology-Seminars and Original Investigations” (“Urologic Oncology”), “Urology”, “The Journal of Urology”, and “World Journal of Urology” were chosen, because these journals publish articles in all four categories. The publication policies of the six journals were very heterogeneous during the time period from 2002 to 2010. The percentage of original experimental and original clinical articles, related to all categories, remained the same in “British Journal of Urology International”, “Urologic Oncology”, “Urology” and “The Journal of Urology”. The percentage of experimental reports in “World Journal of Urology” between 2002–2010 significantly increased from 10 to 20%. A distinct elevation in the percentage of commentarial articles accompanied by a reduction of clinical articles became evident in “European Urology” which significantly correlated with a large increase in the journal’s impact factor. No clearly superior policy could be identified with regard to a general increase in the impact factors from all the journals. The publication policy of urologic journals does not expressly reflect the increase in scientific knowledge, which has occurred over the period 2002–2010. One way of increasing the exposure of urologists to research and expand the interface between experimental and clinical research, would be to enlarge the percentage of experimental articles published. There is no indication that such policy would be detrimental to a journal’s impact factor

Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo

Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into “responders” and “non-responders” to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC

Characterization of Testing Locations for Developing Cool-Season Grass Species

The identification of best testing locations facilitates the allocation of resources in a breeding program, allowing emphasis to be placed at the sites best suited for identifying superior plant materials for the target environment. The objective of this study was the identification of best locations for the evaluation and testing of cool-season grass species within the Northern Great Plains and Intermountain regions of the USA. This study also sought to subdivide the locations into meaningful environmental groupings based on similar entry performance. The study characterized initial stand frequency and forage production (over a 3-yr period) of crested wheatgrass [Agropyron cristatum (L.) Gaertn.; A. desertorum (Fisch. ex Link) Schultes; A. fragile (Roth) Candargy], intermediate wheatgrass [Thinopyrum intermedium (Host) Barkworth & D.R. Dewey], and smooth bromegrass (Bromus inermis Leyss.) at six locations within these regions. Results suggested the existence of best testing locations and environmental groupings for each of the species. For example, the Ithaca, NE, location was consistently a good location for testing forage production. Although there were some consistencies, generally, the best testing locations and environmental groupings were species and trait specific. Thus, the targeted use of locations appeared to be most useful on an individual species basis, rather than considered across the cool-season grass species

EDITH - experimental in-torus maintenance system for fusion reactors. Final report

Experimentelles Handhabungssystem für Wartungsarbeiten im Torus eines Fusionsreaktors Wegen der besonderen Umgebungsbedingungen - erhöhte -Strahlung und Temperatur - können Reparaturarbeiten in der Plasmakammer eines Fusionsreaktors wie NET/ITER nur mittels eines fernbedienten Handhabungssystems durchgeführt werden. EDITH (Experimental Device for In-Torus Handling) ist der Prototyp eines solchen Systems. Es basiert auf einem Vielgelenkarm, der für die jeweiligen Aufgaben mit verschiedenen Endeffektoren bzw. Werkzeugen ausgerüstet ist. EDITH ist die zentrale Komponente eines Teststandes, mit dem in Originalgröße in einem nachgebildeten Ausschnitt einer Plasmakammer Fernhantierungsvorgänge experimentell untersucht werden. Exemplarisch für solche Aufgaben wurde der fernbediente Austausch von Schutzziegeln und Divertorplatten durchgeführt. Um den Operateuren eine schnelle und zuverlässige Durchführung der Arbeiten zu ermöglichen, wurde ein neuartiges Leit- und Steuersystem entwickelt. Das Leitsystem bildet in Form einer Fernhandhabungs-Arbeitsstation zusammen mit den Servomanipulatoren die Mensch-Maschine-Schnittstelle zur Steuerung und Überwachung aller Geräte. Die Arbeitsstation unterstützt die Operateure bei allen manuell zu steuernden Arbeiten, bei der Planung, Simulation und Programmierung automatisch durchzuführender Teilaufgaben und dient mit ihrem multimedialen Dokumentationssystem als ständig verfügbare Informationsquelle. Bei der Konzeption der Steuerung standen das dynamische Verhalten, die Betriebssicherheit und die Kopplung an das Leitsystem im Vordergrund. Qualifikationstests und erste Experimentiererfahrungen bestätigten, daß mit der bei FZK entwickelten Fernhantierungstechnik die gestellten Aufgaben sicher, zuverlässig und in vertretbarer Zeit ausgeführt werden können

Looking ahead: forecasting and planning for the longer-range future, April 1, 2, and 3, 2005

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring Conference that took place during April 1, 2, and 3, 2005.The conference allowed for many highly esteemed scholars and professionals from a broad range of fields to come together to discuss strategies designed for the 21st century and beyond. The speakers and discussants covered a broad range of subjects including: long-term policy analysis, forecasting for business and investment, the National Intelligence Council Global Trends 2020 report, Europe’s transition from the Marshal plan to the EU, forecasting global transitions, foreign policy planning, and forecasting for defense

Multiple origins of hydrogenosomes:functional and phylogenetic evidence from the ADP/ATP carrier of the anaerobic chytrid Neocallimastix sp.

A mitochondrial-type ADP/ATP carrier (AAC) has been identified in the hydrogenosomes of the anaerobic chytridiomycete fungus Neocallimastix sp. L2. Biochemical and immunocytochemical studies revealed that this ADP/ATP carrier is an integral component of hydrogenosomal membranes. Expression of the corresponding cDNA in Escherichia coli confers the ability on the bacterial host to incorporate ADP at significantly higher rates than ATP - similar to isolated mitochondria of yeast and animals. Phylogenetic analysis of this AAC gene (hdgaac ) confirmed with high statistical support that the hydrogenosomal ADP/ATP carrier of Neocallimastix sp. L2 belongs to the family of veritable mitochondrial-type AACs. Hydrogenosome-bearing anaerobic ciliates possess clearly distinct mitochondrial-type AACs, whereas the potential hydrogenosomal carrier Hmp31 of the anaerobic flagellate Trichomonas vaginalis and its homologue from Trichomonas gallinae do not belong to this family of proteins. Also, phylogenetic analysis of genes encoding mitochondrial-type chaperonin 60 proteins (HSP 60) supports the conclusion that the hydrogenosomes of anaerobic chytrids and anaerobic ciliates had independent origins, although both of them arose from mitochondria

Immersive multi-user decision training games with ARLearn

Serious gaming approaches so far focus mainly on skill development, motivational aspects or providing immersive learning situations. Little work has been reported to foster awareness and decision competencies in complex deci-sion situations involving incomplete information and multiple stakeholders. We address this issue exploring the technical requirements and possibilities to de-sign games for such situations in three case studies: a hostage taking situation, a multi-stakeholder logistics case, and a health-care related emergency case. To implement the games, we use a multi-user enabled mobile game development platform (ARLearn). We describe the underlying real world situations and edu-cational challenges and analyse how these are reflected in the ARLearn games realized. Based on these cases we propose a way to increase the immersiveness of mobile learning games.SALOM

Mechanisms behind temsirolimus resistance causing reactivated growth and invasive behavior of bladder cancer cells in vitro

Background: Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy. This study evaluates mechanisms leading to resistance. Methods: Cell growth, proliferation, cell cycle phases, and cell cycle regulating proteins were compared in temsirolimus resistant (res) and sensitive (parental—par) RT112 and UMUC3 bladder cancer cells. To evaluate invasive behavior, adhesion to vascular endothelium or to immobilized extracellular matrix proteins and chemotactic activity were examined. Integrin α and β subtypes were analyzed and blocking was done to evaluate physiologic integrin relevance. Results: Growth of RT112res could no longer be restrained by temsirolimus and was even enhanced in UMUC3res, accompanied by accumulation in the S- and G2/M-phase. Proteins of the cdk-cyclin and Akt-mTOR axis increased, whereas p19, p27, p53, and p73 decreased in resistant cells treated with low-dosed temsirolimus. Chemotactic activity of RT112res/UMUC3res was elevated following temsirolimus re-exposure, along with significant integrin α2, α3, and β1 alterations. Blocking revealed a functional switch of the integrins, driving the resistant cells from being adhesive to being highly motile. Conclusion: Temsirolimus resistance is associated with reactivation of bladder cancer growth and invasive behavior. The α2, α3, and β1 integrins could be attractive treatment targets to hinder temsirolimus resistance