The Potential Use of Electrochemotherapy in the Treatment of Uveal Melanoma: In Vitro Results in 3D Tumor Cultures and In Vivo Results in a Chick Embryo Model

Uveal melanoma (UM) is the most common primary intraocular tumor that arises from neoplastic melanocytes in the choroid, iris, and ciliary body. Electrochemotherapy (ECT) has been successfully established for the treatment of skin and soft tissue metastatic lesions, deep-seated tumors of the liver, bone metastases, and unresectable pancreas lesions. The aim of this study was to evaluate the effect of ECT in vitro in 3D spheroid culture systems in primary and metastatic UM cell lines. We also investigated the chick embryo chorioallantoic membrane (CAM) as an in vivo model system for the growth and treatment of UM tumors using ECT. The cytotoxic effect of ECT in 3D spheroids was analyzed seven days following treatment by assessment of the size and MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction] assay. The cytotoxicity of ECT after intratumoral or intraarterial administration was evaluated histologically. In vitro and in vivo ECT caused a significant reduction in tumor size and viability compared to electroporation or chemotherapy in both sections of our study. The current results underline the effectiveness of ECT in the treatment of UM and prepare the way for further investigation of its potential application in UM

The DLR TuLam project: design of a short and medium range transport aircraft with forward swept NLF wing

In order to further raise the Technology Readiness Level (TRL) of laminar technologies in aircraft design the German Aerospace Center DLR conducted an internal project called TuLam (Toughen up Laminar Technology), which lasted from 2014 to 2017. In the course of the project two technology paths were pursued, namely Natural Laminar Flow (NLF) and Hybrid Laminar Flow Control (HLFC). Within the frame of the NLF path a short and medium range transport aircraft with forward swept laminar wing was designed. The present paper is focused on the aerodynamic design of the forward swept wing in cruise flight. As a special feature in comparison with previous designs of transonic laminar flow wings a trailing edge flap of 10% chord depth is employed to allow for an adaptation of the laminar bucket to off-design conditions. The resulting wing was assessed on overall aircraft level with respect to its fuel reduction potential, whereby the CSR-01 configuration, essentially a re-design of the Airbus A320-200, was used as a reference

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging

Nachhaltigkeit im industriellen Umfeld

Im Rahmen der Lehrveranstaltung "Nachhaltigkeit im industriellen Umfeld" im Masterstudiengang Umwelt- und Verfahrenstechnik der Hochschulen Konstanz und Ravensburg-Weingarten wurde 2015 eine studentische Fachkonferenz durchgeführt. Die Studierenden entwickelten in Einzelarbeit oder als Zweierteam Konferenzbeiträge zu folgenden Themen: - Innovationen und Spannendes aus dem Bereich der Energieerzeugung und -wandlung - Aspekte der Schließung von Stoffkreisläufen und Vermeidung von Schadstoffeinträgen in die Umwelt - Chancen und Herausforderungen Nachwachsender Rohstoffe bei verschiedenen Einsatzmöglichkeiten sowie Themen der Nachhaltigkeit in der Landwirtschaft - verschiedene Blickwinkel auf das Thema Wasser (von der Abwasserreinigung bis zum Wasserkonsum der Konsumenten) - die Betrachtung spezifischer Industrien und Unternehmen sowie deren Werkzeuge zur Umsetzung von Nachhaltigkeit Die Ergebnisse der studentischen Fachkonferenz zur „Nachhaltigkeit im industriellen Umfeld“ werden in der vorliegenden Publikation präsentiert

A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.

Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion

Community-developed checklists for publishing images and image analysis

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However for scientists wishing to publish the obtained images and image analyses results, there are to date no unified guidelines. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here we present community-developed checklists for preparing light microscopy images and image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality of microscopy data is in publications.Comment: 28 pages, 8 Figures, 3 Supplmentary Figures, Manuscript, Essential recommendations for publication of microscopy image dat

Common characteristics of open source software development and applicability for drug discovery: a systematic review

<p>Abstract</p> <p>Background</p> <p>Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery.</p> <p>Methods</p> <p>A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project.</p> <p>Results</p> <p>Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined.</p> <p>Conclusions</p> <p>We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.</p