A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy

A Parallel Distributed Strategy for Arraying a Scattered Robot Swarm

We consider the problem of organizing a scattered group of $n$ robots in two-dimensional space, with geometric maximum distance $D$ between robots. The communication graph of the swarm is connected, but there is no central authority for organizing it. We want to arrange them into a sorted and equally-spaced array between the robots with lowest and highest label, while maintaining a connected communication network. In this paper, we describe a distributed method to accomplish these goals, without using central control, while also keeping time, travel distance and communication cost at a minimum. We proceed in a number of stages (leader election, initial path construction, subtree contraction, geometric straightening, and distributed sorting), none of which requires a central authority, but still accomplishes best possible parallelization. The overall arraying is performed in $O(n)$ time, $O(n^2)$ individual messages, and $O(nD)$ travel distance. Implementation of the sorting and navigation use communication messages of fixed size, and are a practical solution for large populations of low-cost robots

Distributed control and navigation system for quadrotor UAVs in GPS-denied environments

The problem of developing distributed control and navigation system for quadrotor UAVs operating in GPS-denied environments is addressed in the paper. Cooperative navigation, marker detection and mapping task solved by a team of multiple unmanned aerial vehicles is chosen as demo example. Developed intelligent control system complies with on 4D\RCS reference model and its implementation is based on ROS framework. Custom implementation of EKF-based map building algorithm is used to solve marker detection and map building task.Comment: Camera-ready as submitted (and accepted) to the 7th IEEE International Conference Intelligent Systems IS'2014, September 24-26, 2014, Warsaw, Polan

A Survey and Analysis of Multi-Robot Coordination

International audienceIn the field of mobile robotics, the study of multi-robot systems (MRSs) has grown significantly in size and importance in recent years. Having made great progress in the development of the basic problems concerning single-robot control, many researchers shifted their focus to the study of multi-robot coordination. This paper presents a systematic survey and analysis of the existing literature on coordination, especially in multiple mobile robot systems (MMRSs). A series of related problems have been reviewed, which include a communication mechanism, a planning strategy and a decision-making structure. A brief conclusion and further research perspectives are given at the end of the paper

The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level.

The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multicentre study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in 5 different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organisation. We detected changes in chromatin organisation in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity, and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings

Are Autonomous Mobile Robots Able to Take Over Construction? A Review

Although construction has been known as a highly complex application field for autonomous robotic systems, recent advances in this field offer great hope for using robotic capabilities to develop automated construction. Today, space research agencies seek to build infrastructures without human intervention, and construction companies look to robots with the potential to improve construction quality, efficiency, and safety, not to mention flexibility in architectural design. However, unlike production robots used, for instance, in automotive industries, autonomous robots should be designed with special consideration for challenges such as the complexity of the cluttered and dynamic working space, human-robot interactions and inaccuracy in positioning due to the nature of mobile systems and the lack of affordable and precise self-positioning solutions. This paper briefly reviews state-ofthe-art research into automated construction by autonomous mobile robots. We address and classify the relevant studies in terms of applications, materials, and robotic systems. We also identify ongoing challenges and discuss about future robotic requirements for automated construction

LinkMind: Link Optimization in Swarming Mobile Sensor Networks

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation