Heart failure gene therapy: the path to clinical practice

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

Medical image computing in diagnosis and intervention of spinal diseases

Spinal image analysis and computer assisted intervention have emerged as new and independent research areas, due to the importance of treatment of spinal diseases, increasing availability of spinal imaging, and advances in analytics and navigation tools. Among others, multiple modality spinal image analysis and spinal navigation tools have emerged as two keys in this new area. We believe that further focused research in these two areas will lead to a much more efficient and accelerated research path, avoiding detours that exist in other applications, such as in brain and heart.

Gradient-domain Path Tracing

We introduce gradient-domain rendering for Monte Carlo image synthesis.While previous gradient-domain Metropolis Light Transport sought to distribute more samples in areas of high gradients, we show, in contrast, that estimating image gradients is also possible using standard (non-Metropolis) Monte Carlo algorithms, and furthermore, that even without changing the sample distribution, this often leads to significant error reduction. This broadens the applicability of gradient rendering considerably. To gain insight into the conditions under which gradient-domain sampling is beneficial, we present a frequency analysis that compares Monte Carlo sampling of gradients followed by Poisson reconstruction to traditional Monte Carlo sampling. Finally, we describe Gradient-Domain Path Tracing (G-PT), a relatively simple modification of the standard path tracing algorithm that can yield far superior results.

DEVELOPMENT OF A BEAM-SPECIFIC PLANNING TARGET VOLUME AND A ROBUST PLAN ANALYSIS TOOL FOR PROTON THERAPY

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of this dissertation research was to develop a treatment planning method and a planevaluation method that address proton-specific issues regarding setup and range uncertainties. Treatment plan designing method adapted to proton therapy: Currently, for proton therapy using a scanning beam delivery system, setup uncertainties are largely accounted for by geometrically expanding a clinical target volume (CTV) to a planning target volume (PTV). However, a PTV alone cannot adequately account for range uncertainties coupled to misaligned patient anatomy in the beam path since it does not account for the change in tissue density. In order to remedy this problem, we proposed a beam-specific PTV (bsPTV) that accounts for the change in tissue density along the beam path due to the uncertainties. Our proposed method was successfully implemented, and its superiority over the conventional PTV was shown through a controlled experiment.. Furthermore, we have shown that the bsPTV concept can be incorporated into beam angle optimization for better target coverage and normal tissue sparing for a selected lung cancer patient. Treatment plan evaluation method adapted to proton therapy: The dose-volume histogram of the clinical target volume (CTV) or any other volumes of interest at the time of planning does not represent the most probable dosimetric outcome of a given plan as it does not include the uncertainties mentioned earlier. Currently, the PTV is used as a surrogate of the CTV’s worst case scenario for target dose estimation. However, because proton dose distributions are subject to change under these uncertainties, the validity of the PTV analysis method is questionable. In order to remedy this problem, we proposed the use of statistical parameters to quantify uncertainties on both the dose-volume histogram and dose distribution directly. The robust plan analysis tool was successfully implemented to compute both the expectation value and its standard deviation of dosimetric parameters of a treatment plan under the uncertainties. For 15 lung cancer patients, the proposed method was used to quantify the dosimetric difference between the nominal situation and its expected value under the uncertainties.

A waypoint-based mission planner for a farmland coverage with an aerial robot - a precision farming tool

Remote sensing (RS) with aerial robots is becoming more usual in every day time in Precision Agriculture (PA) practices, do to their advantages over conventional methods. Usually, available commercial platforms providing off-the-shelf waypoint navigation are adopted to perform visual surveys over crop fields, with the purpose to acquire specific image samples. The way in which a waypoint list is computed and dispatched to the aerial robot when mapping non empty agricultural workspaces has not been yet discussed. In this paper we propose an offline mission planner approach that computes an efficient coverage path subject to some constraints by decomposing the environment approximately into cells. Therefore, the aim of this work is contributing with a feasible waypoints-based tool to support PA practices

Aerial Remote Sensing in Agriculture: A Practical Approach to Area Coverage and Path Planning for Fleets of Mini Aerial Robots

In this paper, a system that allows applying precision agriculture techniques is described. The application is based on the deployment of a team of unmanned aerial vehicles that are able to take georeferenced pictures in order to create a full map by applying mosaicking procedures for postprocessing. The main contribution of this work is practical experimentation with an integrated tool. Contributions in different fields are also reported. Among them is a new one-phase automatic task partitioning manager, which is based on negotiation among the aerial vehicles, considering their state and capabilities. Once the individual tasks are assigned, an optimal path planning algorithm is in charge of determining the best path for each vehicle to follow. Also, a robust flight control based on the use of a control law that improves the maneuverability of the quadrotors has been designed. A set of field tests was performed in order to analyze all the capabilities of the system, from task negotiations to final performance. These experiments also allowed testing control robustness under different weather conditions.

IDRA (IDeal Resource Allocation): Computing ideal speedups in parallel logic programming

We present a technique to estimate accurate speedups for parallel logic programs with relative independence from characteristics of a given implementation or underlying parallel hardware. The proposed technique is based on gathering accurate data describing one execution at run-time, which is fed to a simulator. Alternative schedulings are then simulated and estimates computed for the corresponding speedups. A tool implementing the aforementioned techniques is presented, and its predictions are compared to the performance of real systems, showing good correlation.

Dreams: A tool for the design of dynamically reconfigurable embedded and modular systems

Dynamically Reconfigurable Systems are attracting a growing interest, mainly due to the emergence of novel applications based on this technology. However, commercial tools do not provide enough flexibility to design solutions, while keeping an acceptable design productivity. In this paper, a novel design flow is proposed, targeting dynamically reconfigurable systems. It is fully supported by a tool called Dreams, which is able to implement flexible systems, starting from a set of netlists corresponding to the modules, as well as a system description provided by the user. The tool automatically post-processes the nets, implementing a solution for the communications between reconfigurable regions, as well as the handling of routing conflicts, by means of a custom router. Since the design process of every module and the static system are independent, the proposed flow is compatible with system upgrade at run-time. In this paper, a use case corresponding to the design of a highly regular and parallel mesh-type architecture is described, in order to show the architectural flexibility offered by the tool.

A graphical tool for designing interactive video cognitive rehabilitation therapies

Acquired Brain Injury (ABI) has become one of the most common causes of neurological disability in developed countries. Cognitive disorders result in a loss of independence and therefore patients? quality of life. Cognitive rehabilitation aims to promote patients? skills to achieve their highest degree of personal autonomy. New technologies such as interactive video, whereby real situations of daily living are reproduced within a controlled virtual environment, enable the design of personalized therapies with a high level of generalization and a great ecological validity. This paper presents a graphical tool that allows neuropsychologists to design, modify, and configure interactive video therapeutic activities, through the combination of graphic and natural language. The tool has been validated creating several Activities of Daily Living and a preliminary usability evaluation has been performed showing a good clinical acceptance in the definition of complex interactive video therapies for cognitive rehabilitation.

Aerial Coverage Path Planning applied to Mapping

In the last decade we have seen how small and light weight aerial platforms - aka, Mini Unmanned Aerial Vehicles (MUAV) - shipped with heterogeneous sensors have become a 'most wanted' Remote Sensing (RS) tool. Most of the off-the-shelf aerial systems found in the market provide way-point navigation. However, they do not rely on a tool that compute the aerial trajectories considering all the aspects that allow optimizing the aerial missions. One of the most demanded RS applications of MUAV is image surveying. The images acquired are typically used to build a high-resolution image, i.e., a mosaic of the workspace surface. Although, it may be applied to any other application where a sensor-based map must be computed. This thesis provides a study of this application and a set of solutions and methods to address this kind of aerial mission by using a fleet of MUAVs. In particular, a set of algorithms are proposed for map-based sampling, and aerial coverage path planning (ACPP). Regarding to map-based sampling, the approaches proposed consider workspaces with different shapes and surface characteristics. The workspace is sampled considering the sensor characteristics and a set of mission requirements. The algorithm applies different computational geometry approaches, providing a unique way to deal with workspaces with different shape and surface characteristics in order to be surveyed by one or more MUAVs. This feature introduces a previous optimization step before path planning. After that, the ACPP problem is theorized and a set of ACPP algorithms to compute the MUAVs trajectories are proposed. The problem addressed herein is the problem to coverage a wide area by using MUAVs with limited autonomy. Therefore, the mission must be accomplished in the shortest amount of time. The aerial survey is usually subject to a set of workspace restrictions, such as the take-off and landing positions as well as a safety distance between elements of the fleet. Moreover, it has to avoid forbidden zones to y. Three different algorithms have been studied to address this problem. The approaches studied are based on graph searching, heuristic and meta-heuristic approaches, e.g., mimic, evolutionary. Finally, an extended survey of field experiments applying the previous methods, as well as the materials and methods adopted in outdoor missions is presented. The reported outcomes demonstrate that the findings attained from this thesis improve ACPP mission for mapping purpose in an efficient and safe manner.

Aerial Coverage Path Planning applied to Mapping

In the last decade we have seen how small and light weight aerial platforms - aka, Mini Unmanned Aerial Vehicles (MUAV) - shipped with heterogeneous sensors have become a 'most wanted' Remote Sensing (RS) tool. Most of the off-the-shelf aerial systems found in the market provide way-point navigation. However, they do not rely on a tool that compute the aerial trajectories considering all the aspects that allow optimizing the aerial missions. One of the most demanded RS applications of MUAV is image surveying. The images acquired are typically used to build a high-resolution image, i.e., a mosaic of the workspace surface. Although, it may be applied to any other application where a sensor-based map must be computed. This thesis provides a study of this application and a set of solutions and methods to address this kind of aerial mission by using a fleet of MUAVs. In particular, a set of algorithms are proposed for map-based sampling, and aerial coverage path planning (ACPP). Regarding to map-based sampling, the approaches proposed consider workspaces with different shapes and surface characteristics. The workspace is sampled considering the sensor characteristics and a set of mission requirements. The algorithm applies different computational geometry approaches, providing a unique way to deal with workspaces with different shape and surface characteristics in order to be surveyed by one or more MUAVs. This feature introduces a previous optimization step before path planning. After that, the ACPP problem is theorized and a set of ACPP algorithms to compute the MUAVs trajectories are proposed. The problem addressed herein is the problem to coverage a wide area by using MUAVs with limited autonomy. Therefore, the mission must be accomplished in the shortest amount of time. The aerial survey is usually subject to a set of workspace restrictions, such as the take-off and landing positions as well as a safety distance between elements of the fleet. Moreover, it has to avoid forbidden zones to y. Three different algorithms have been studied to address this problem. The approaches studied are based on graph searching, heuristic and meta-heuristic approaches, e.g., mimic, evolutionary. Finally, an extended survey of field experiments applying the previous methods, as well as the materials and methods adopted in outdoor missions is presented. The reported outcomes demonstrate that the findings attained from this thesis improve ACPP mission for mapping purpose in an efficient and safe manner.

Distributed, layered and reliable computing nets to represent neuronal receptive fields

Abstract. Receptive fields of retinal and other sensory neurons show a large variety of spatiotemporal linear and non linear types of responses to local stimuli. In visual neurons, these responses present either asymmetric sensitive zones or center-surround organization. In most cases, the nature of the responses suggests the existence of a kind of distributed computation prior to the integration by the final cell which is evidently supported by the anatomy. We describe a new kind of discrete and continuous filters to model the kind of computations taking place in the receptive fields of retinal cells. To show their performance in the analysis of diferent non-trivial neuron-like structures, we use a computer tool specifically programmed by the authors to that efect. This tool is also extended to study the efect of lesions on the whole performance of our model nets.

GovCloud: the usage of cloud computing in public organizations

It has been shown that cloud computing brings cost benefits and promotes efficiency in the operations of the organizations, no matter what their type or size. However, few public organizations are benefiting from this new paradigm shift in the way the organizations consume and manage computational resources. The objective of this thesis is to analyze both internal and external factors that may influence the adoption of cloud computing by public organizations and propose possible strategies that can assist these organizations in their path to cloud usage. In order to achieve this objective, a SWOT analysis has been conducted, detecting internal factors (strengths and weaknesses) and external factors (opportunities and threats) that can influence the adoption of a governmental cloud. With the application of a TOWS matrix, by combining the internal and external factors, a list of possible strategies have been formulated to be used as a guide to decision-making related to the transition to a cloud environment.

Development of a Digital Tool to Overcome the Challenges of Rural Food SMEs

Peer reviewed

An analysis of scheduling algorithms in multiprocessor computing systems /

"UIUCDCS-R-75-724"