Retroviral Integrations in Gene Therapy Trials

γ-Retroviral and lentiviral vectors allow the permanent integration of a therapeutic transgene in target cells and have provided in the last decade a delivery platform for several successful gene therapy (GT) clinical approaches. However, the occurrence of adverse events due to insertional mutagenesis in GT treated patients poses a strong challenge to the scientific community to identify the mechanisms at the basis of vector-driven genotoxicity. Along the last decade, the study of retroviral integration sites became a fundamental tool to monitor vector–host interaction in patients overtime. This review is aimed at critically revising the data derived from insertional profiling, with a particular focus on the evidences collected from GT clinical trials. We discuss the controversies and open issues associated to the interpretation of integration site analysis during patient's follow up, with an update on the latest results derived from the use of high-throughput technologies. Finally, we provide a perspective on the future technical development and on the application of these studies to address broader biological questions, from basic virology to human hematopoiesis

The role of concurrency in an evolutionary view of programming abstractions

In this paper we examine how concurrency has been embodied in mainstream programming languages. In particular, we rely on the evolutionary talking borrowed from biology to discuss major historical landmarks and crucial concepts that shaped the development of programming languages. We examine the general development process, occasionally deepening into some language, trying to uncover evolutionary lineages related to specific programming traits. We mainly focus on concurrency, discussing the different abstraction levels involved in present-day concurrent programming and emphasizing the fact that they correspond to different levels of explanation. We then comment on the role of theoretical research on the quest for suitable programming abstractions, recalling the importance of changing the working framework and the way of looking every so often. This paper is not meant to be a survey of modern mainstream programming languages: it would be very incomplete in that sense. It aims instead at pointing out a number of remarks and connect them under an evolutionary perspective, in order to grasp a unifying, but not simplistic, view of the programming languages development process

Architecture of Environmental Risk Modelling: for a faster and more robust response to natural disasters

Demands on the disaster response capacity of the European Union are likely to increase, as the impacts of disasters continue to grow both in size and frequency. This has resulted in intensive research on issues concerning spatially-explicit information and modelling and their multiple sources of uncertainty. Geospatial support is one of the forms of assistance frequently required by emergency response centres along with hazard forecast and event management assessment. Robust modelling of natural hazards requires dynamic simulations under an array of multiple inputs from different sources. Uncertainty is associated with meteorological forecast and calibration of the model parameters. Software uncertainty also derives from the data transformation models (D-TM) needed for predicting hazard behaviour and its consequences. On the other hand, social contributions have recently been recognized as valuable in raw-data collection and mapping efforts traditionally dominated by professional organizations. Here an architecture overview is proposed for adaptive and robust modelling of natural hazards, following the Semantic Array Programming paradigm to also include the distributed array of social contributors called Citizen Sensor in a semantically-enhanced strategy for D-TM modelling. The modelling architecture proposes a multicriteria approach for assessing the array of potential impacts with qualitative rapid assessment methods based on a Partial Open Loop Feedback Control (POLFC) schema and complementing more traditional and accurate a-posteriori assessment. We discuss the computational aspect of environmental risk modelling using array-based parallel paradigms on High Performance Computing (HPC) platforms, in order for the implications of urgency to be introduced into the systems (Urgent-HPC).Comment: 12 pages, 1 figure, 1 text box, presented at the 3rd Conference of Computational Interdisciplinary Sciences (CCIS 2014), Asuncion, Paragua

Neuro-memristive Circuits for Edge Computing: A review

The volume, veracity, variability, and velocity of data produced from the ever-increasing network of sensors connected to Internet pose challenges for power management, scalability, and sustainability of cloud computing infrastructure. Increasing the data processing capability of edge computing devices at lower power requirements can reduce several overheads for cloud computing solutions. This paper provides the review of neuromorphic CMOS-memristive architectures that can be integrated into edge computing devices. We discuss why the neuromorphic architectures are useful for edge devices and show the advantages, drawbacks and open problems in the field of neuro-memristive circuits for edge computing

On Neuromechanical Approaches for the Study of Biological Grasp and Manipulation

Biological and robotic grasp and manipulation are undeniably similar at the level of mechanical task performance. However, their underlying fundamental biological vs. engineering mechanisms are, by definition, dramatically different and can even be antithetical. Even our approach to each is diametrically opposite: inductive science for the study of biological systems vs. engineering synthesis for the design and construction of robotic systems. The past 20 years have seen several conceptual advances in both fields and the quest to unify them. Chief among them is the reluctant recognition that their underlying fundamental mechanisms may actually share limited common ground, while exhibiting many fundamental differences. This recognition is particularly liberating because it allows us to resolve and move beyond multiple paradoxes and contradictions that arose from the initial reasonable assumption of a large common ground. Here, we begin by introducing the perspective of neuromechanics, which emphasizes that real-world behavior emerges from the intimate interactions among the physical structure of the system, the mechanical requirements of a task, the feasible neural control actions to produce it, and the ability of the neuromuscular system to adapt through interactions with the environment. This allows us to articulate a succinct overview of a few salient conceptual paradoxes and contradictions regarding under-determined vs. over-determined mechanics, under- vs. over-actuated control, prescribed vs. emergent function, learning vs. implementation vs. adaptation, prescriptive vs. descriptive synergies, and optimal vs. habitual performance. We conclude by presenting open questions and suggesting directions for future research. We hope this frank assessment of the state-of-the-art will encourage and guide these communities to continue to interact and make progress in these important areas

Transdisciplinarity seen through Information, Communication, Computation, (Inter-)Action and Cognition

Similar to oil that acted as a basic raw material and key driving force of industrial society, information acts as a raw material and principal mover of knowledge society in the knowledge production, propagation and application. New developments in information processing and information communication technologies allow increasingly complex and accurate descriptions, representations and models, which are often multi-parameter, multi-perspective, multi-level and multidimensional. This leads to the necessity of collaborative work between different domains with corresponding specialist competences, sciences and research traditions. We present several major transdisciplinary unification projects for information and knowledge, which proceed on the descriptive, logical and the level of generative mechanisms. Parallel process of boundary crossing and transdisciplinary activity is going on in the applied domains. Technological artifacts are becoming increasingly complex and their design is strongly user-centered, which brings in not only the function and various technological qualities but also other aspects including esthetic, user experience, ethics and sustainability with social and environmental dimensions. When integrating knowledge from a variety of fields, with contributions from different groups of stakeholders, numerous challenges are met in establishing common view and common course of action. In this context, information is our environment, and informational ecology determines both epistemology and spaces for action. We present some insights into the current state of the art of transdisciplinary theory and practice of information studies and informatics. We depict different facets of transdisciplinarity as we see it from our different research fields that include information studies, computability, human-computer interaction, multi-operating-systems environments and philosophy.Comment: Chapter in a forthcoming book: Information Studies and the Quest for Transdisciplinarity - Forthcoming book in World Scientific. Mark Burgin and Wolfgang Hofkirchner, Editor

Data-driven modelling of biological multi-scale processes

Biological processes involve a variety of spatial and temporal scales. A holistic understanding of many biological processes therefore requires multi-scale models which capture the relevant properties on all these scales. In this manuscript we review mathematical modelling approaches used to describe the individual spatial scales and how they are integrated into holistic models. We discuss the relation between spatial and temporal scales and the implication of that on multi-scale modelling. Based upon this overview over state-of-the-art modelling approaches, we formulate key challenges in mathematical and computational modelling of biological multi-scale and multi-physics processes. In particular, we considered the availability of analysis tools for multi-scale models and model-based multi-scale data integration. We provide a compact review of methods for model-based data integration and model-based hypothesis testing. Furthermore, novel approaches and recent trends are discussed, including computation time reduction using reduced order and surrogate models, which contribute to the solution of inference problems. We conclude the manuscript by providing a few ideas for the development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and Multiscale Dynamics (American Scientific Publishers