Axel Mobility Platform for Steep Terrain Excursions and Sampling on Planetary Surfaces

The recent discovery of bright new deposits in two crater gullies on Mars suggests that water still flows in brief spurts on Mars. In this paper, we will present the Axel rover (Figure 1) that was developed to access and sample such deposits on the inside of steep crater walls. Axel is a tethered rover that can be a payload on a lander or a larger rover. The primary features of Axel are its minimal complexity and robustness to the treacherous terrain of sites that are of scientific interest. Using a symmetrical design with three actuators, Axel is capable of operating upside down and right side up, enabling it to descend over crater promontories. With its actuated trailing link, Axel can operate on both flat and sloped terrains. Using a sampling device mounted on the trailing link, Axel can collect and store terrain samples and return to its host platform for detailed scientific sample analysis. We will present our preliminary results that demonstrated Axel's ability to traverse both flat and sloped rocky terrain including 90° vertical cliffs and collecting soil samples on slopes ranging from 10° - 40° in the JPL Mars Yard

Intervertebral disc regeneration: Influence of growth factors on differentiation of human mesenchymal stem cells (hMSC)

Introduction: One common cause of disability in modern society is low back pain. The main reason for this pain is the degeneration of the intervertebral disc (IVD), particular of the nucleus pulposus (NP). For an early degeneration stage cell-based therapy would be a minimal invasive method of treatment. Therefore, adequate cells are needed. As the usage of NP cells is limited because of their insufficient amount or vitality, a promising alternative is the application of human mesenchymal stem cells (hMSCs). Objective: To investigate the potential of various growth factors to induce the differentiation of hMSCs into NP cells and thereby to obtain an alternative cell source for the treatment of IVD degeneration. Methods: hMSC-TERT were cultivated three-dimensionally in a hydrogel for 21 days to form NP cells. Cell survival and proliferation were determined using SybrGreen/propidium iodide double staining and the WST-test. To investigate the ability of several growth factors to differentiate hMSCs into NP cells, fluorescence immunostaining of NP-specific marker proteins (e.g. chondroadherin (CHAD) and the recently discovered cytokeratin 19 [1]) was performed. Results: Following the procedure described above, cells are able to maintain their viability and proliferation capacity throughout the cultivation time. By using a previously established immunofluorescence protocol, we could indicate the ability of three different growth factors to differentiate hMSCs into NP-like cells. Conclusion: The expression of several marker proteins in all differentiation experiments indicates the ability of IGF-1, FGF-2 and PDGF-BB to differentiate hMSCs into NP-like cells apart from the usually applied TGF-β3. Furthermore, our findings preclude the application of Cytokeratin 19 as a specific marker protein for NP cells [1]. Further experiments have to be done to find real specific NP marker proteins to indisputable verify the differentiation of hMSCs into NP cells. If so, application of the mentioned three growth factors would possibly be an option to obtain sufficient NP cells for minimal invasive IVD regeneration

Safe, long-term hepatic expression of anti-HCV shRNA in a nonhuman primate model

The hepatitis C virus (HCV) chronically infects 2% of the world population and effective treatment is limited by long duration and significant side-effects. Here, we describe a novel drug, intended as a “single-shot ” therapy, which expresses three short hairpin RNAs (shRNAs) that simultaneously target multiple conserved regions of the HCV genome as confirmed in vitro by knockdown of an HCV replicon system. Using a recombinant adeno-associated virus (AAV) serotype 8 vector for delivery, comprehensive transduction of hepatocytes was achieved in vivo in a nonhuman primate (NHP) model following a single intravenous injection. However, dose ranging studies performed in 13 NHP resulted in high-expression levels of shRNA from wild-type (wt) Pol III promoters and dose-dependent hepatocellular toxicity, the first demonstration of shRNA-related toxicity in primates, establishing that the hepatotoxicity arises from highly conserved features of the RNA interference (RNAi) pathway. In the second generation drug, each promoter was re-engineered to reduce shRNA transcription to levels that circumvent toxicity but still inhibit replicon activity. In vivo testing of this modified construct in 18 NHPs showed conservation of hepatocyte transduction but complete elimination of hepatotoxicity, even with sustained shRNA expression for 50 days. These data support progression to a clinical study for treatment of HCV infection

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary