Automatic X-ray landmark detection and shape segmentation via data-driven joint estimation of image displacements

In this paper, we propose a new method for fully-automatic landmark detection and shape segmentation in X-ray images. To detect landmarks, we estimate the displacements from some randomly sampled image patches to the (unknown) landmark positions, and then we integrate these predictions via a voting scheme. Our key contribution is a new algorithm for estimating these displacements. Different from other methods where each image patch independently predicts its displacement, we jointly estimate the displacements from all patches together in a data driven way, by considering not only the training data but also geometric constraints on the test image. The displacements estimation is formulated as a convex optimization problem that can be solved efficiently. Finally, we use the sparse shape composition model as the a priori information to regularize the landmark positions and thus generate the segmented shape contour. We validate our method on X-ray image datasets of three different anatomical structures: complete femur, proximal femur and pelvis. Experiments show that our method is accurate and robust in landmark detection, and, combined with the shape model, gives a better or comparable performance in shape segmentation compared to state-of-the art methods. Finally, a preliminary study using CT data shows the extensibility of our method to 3D data.

Conceptual design and simulation of a water Cherenkov muon veto for the XENON1T experiment

XENON is a dark matter direct detection project, consisting of a time projection chamber (TPC) filled with liquid xenon as detection medium. The construction of the next generation detector, XENON1T, is presently taking place at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. It aims at a sensitivity to spin-independent cross sections of 2 10-47 c 2 for WIMP masses around 50 GeV2, which requires a background reduction by two orders of magnitude compared to XENON100, the current generation detector. An active system that is able to tag muons and muon-induced backgrounds is critical for this goal. A water Cherenkov detector of ~ 10 m height and diameter has been therefore developed, equipped with 8 inch photomultipliers and cladded by a reflective foil. We present the design and optimization study for this detector, which has been carried out with a series of Monte Carlo simulations. The muon veto will reach very high detection efficiencies for muons (>99.5%) and showers of secondary particles from muon interactions in the rock (>70%). Similar efficiencies will be obtained for XENONnT, the upgrade of XENON1T, which will later improve the WIMP sensitivity by another order of magnitude. With the Cherenkov water shield studied here, the background from muon-induced neutrons in XENON1T is negligible.

Optimization of Optical Follow-up Strategies Based on Covariance Analysis

An in-depth study, using simulations and covariance analysis, is performed to identify the optimal sequence of observations to obtain the most accurate orbit propagation. The accuracy of the results of an orbit determination/ improvement process depends on: tracklet length, number of observations, type of orbit, astrometric error, time interval between tracklets and observation geometry. The latter depends on the position of the object along its orbit and the location of the observing station. This covariance analysis aims to optimize the observation strategy taking into account the influence of the orbit shape, of the relative object-observer geometry and the interval between observations.

Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method

Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6-mediated Ca2+-influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D-shape and pharmacophore similarity algorithm, a type of ligand-based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0.3 μM inhibition of TRPV6. The ability of xLOS to identify different scaffolds early in LBVS was essential to success. The xLOS method may be generally useful to develop tool compounds for poorly characterized targets.

Stereological estimation of particle shape and orientation from volume tensors

In the present paper, we describe new robust methods of estimating cell shape and orientation in 3D from sections. The descriptors of 3D cell shape and orientation are based on volume tensors which are used to construct an ellipsoid, the Miles ellipsoid, approximating the average cell shape and orientation in 3D. The estimators of volume tensors are based on observations in several optical planes through sampled cells. This type of geometric sampling design is known as the optical rotator. The statistical behaviour of the estimator of the Miles ellipsoid is studied under a flexible model for 3D cell shape and orientation. In a simulation study, the lengths of the axes of the Miles ellipsoid can be estimated with CVs of about 2% if 100 cells are sampled. Finally, we illustrate the use of the developed methods in an example, involving neurons in the medial prefrontal cortex of rat.

Differentiating the Multipoint Expected Improvement for Optimal Batch Design

This work deals with parallel optimization of expensive objective functions which are modelled as sample realizations of Gaussian processes. The study is formalized as a Bayesian optimization problem, or continuous multi-armed bandit problem, where a batch of q > 0 arms is pulled in parallel at each iteration. Several algorithms have been developed for choosing batches by trading off exploitation and exploration. As of today, the maximum Expected Improvement (EI) and Upper Confidence Bound (UCB) selection rules appear as the most prominent approaches for batch selection. Here, we build upon recent work on the multipoint Expected Improvement criterion, for which an analytic expansion relying on Tallis’ formula was recently established. The computational burden of this selection rule being still an issue in application, we derive a closed-form expression for the gradient of the multipoint Expected Improvement, which aims at facilitating its maximization using gradient-based ascent algorithms. Substantial computational savings are shown in application. In addition, our algorithms are tested numerically and compared to state-of-the-art UCB-based batchsequential algorithms. Combining starting designs relying on UCB with gradient-based EI local optimization finally appears as a sound option for batch design in distributed Gaussian Process optimization.

The design and evaluation of a 2D dose verification system for intensity modulated radiotherapy

The usage of intensity modulated radiotherapy (IMRT) treatments necessitates a significant amount of patient-specific quality assurance (QA). This research has investigated the precision and accuracy of Kodak EDR2 film measurements for IMRT verifications, the use of comparisons between 2D dose calculations and measurements to improve treatment plan beam models, and the dosimetric impact of delivery errors. New measurement techniques and software were developed and used clinically at M. D. Anderson Cancer Center. The software implemented two new dose comparison parameters, the 2D normalized agreement test (NAT) and the scalar NAT index. A single-film calibration technique using multileaf collimator (MLC) delivery was developed. EDR2 film's optical density response was found to be sensitive to several factors: radiation time, length of time between exposure and processing, and phantom material. Precision of EDR2 film measurements was found to be better than 1%. For IMRT verification, EDR2 film measurements agreed with ion chamber results to 2%/2mm accuracy for single-beam fluence map verifications and to 5%/2mm for transverse plane measurements of complete plan dose distributions. The same system was used to quantitatively optimize the radiation field offset and MLC transmission beam modeling parameters for Varian MLCs. While scalar dose comparison metrics can work well for optimization purposes, the influence of external parameters on the dose discrepancies must be minimized. The ability of 2D verifications to detect delivery errors was tested with simulated data. The dosimetric characteristics of delivery errors were compared to patient-specific clinical IMRT verifications. For the clinical verifications, the NAT index and percent of pixels failing the gamma index were exponentially distributed and dependent upon the measurement phantom but not the treatment site. Delivery errors affecting all beams in the treatment plan were flagged by the NAT index, although delivery errors impacting only one beam could not be differentiated from routine clinical verification discrepancies. Clinical use of this system will flag outliers, allow physicists to examine their causes, and perhaps improve the level of agreement between radiation dose distribution measurements and calculations. The principles used to design and evaluate this system are extensible to future multidimensional dose measurements and comparisons. ^

Modified 3+3 design for phase I clinical trials

Phase I clinical trial is mainly designed to determine the maximum tolerated dose (MTD) of a new drug. Optimization of phase I trial design is crucial to minimize the number of enrolled patients exposed to unsafe dose levels and to provide reliable information to the later phases of clinical trials. Although it has been criticized about its inefficient MTD estimation, nowadays the traditional 3+3 method remains dominant in practice due to its simplicity and conservative estimation. There are many new designs that have been proven to generate more credible MTD estimation, such as the Continual Reassessment Method (CRM). Despite its accepted better performance, the CRM design is still not widely used in real trials. There are several factors that contribute to the difficulties of CRM adaption in practice. First, CRM is not widely accepted by the regulatory agencies such as FDA in terms of safety. It is considered to be less conservative and tend to expose more patients above the MTD level than the traditional design. Second, CRM is relatively complex and not intuitive for the clinicians to fully understand. Third, the CRM method take much more time and need statistical experts and computer programs throughout the trial. The current situation is that the clinicians still tend to follow the trial process that they are comfortable with. This situation is not likely to change in the near future. Based on this situation, we have the motivation to improve the accuracy of MTD selection while follow the procedure of the traditional design to maintain simplicity. We found that in 3+3 method, the dose transition and the MTD determination are relatively independent. Thus we proposed to separate the two stages. The dose transition rule remained the same as 3+3 method. After getting the toxicity information from the dose transition stage, we combined the isotonic transformation to ensure the monotonic increasing order before selecting the optimal MTD. To compare the operating characteristics of the proposed isotonic method and the other designs, we carried out 10,000 simulation trials under different dose setting scenarios to compare the design characteristics of the isotonic modified method with standard 3+3 method, CRM, biased coin design (BC) and k-in-a-row design (KIAW). The isotonic modified method improved MTD estimation of the standard 3+3 in 39 out of 40 scenarios. The improvement is much greater when the target is 0.3 other than 0.25. The modified design is also competitive when comparing with other selected methods. A CRM method performed better in general but was not as stable as the isotonic method throughout the different dose settings. The results demonstrated that our proposed isotonic modified method is not only easily conducted using the same procedure as 3+3 but also outperforms the conventional 3+3 design. It can also be applied to determine MTD for any given TTL. These features make the isotonic modified method of practical value in phase I clinical trials.^

EPANET Input Files of New York tunnels and Pacific City used in a metamodel-based optimization study

Metamodels have proven be very useful when it comes to reducing the computational requirements of Evolutionary Algorithm-based optimization by acting as quick-solving surrogates for slow-solving fitness functions. The relationship between metamodel scope and objective function varies between applications, that is, in some cases the metamodel acts as a surrogate for the whole fitness function, whereas in other cases it replaces only a component of the fitness function. This paper presents a formalized qualitative process to evaluate a fitness function to determine the most suitable metamodel scope so as to increase the likelihood of calibrating a high-fidelity metamodel and hence obtain good optimization results in a reasonable amount of time. The process is applied to the risk-based optimization of water distribution systems; a very computationally-intensive problem for real-world systems. The process is validated with a simple case study (modified New York Tunnels) and the power of metamodelling is demonstrated on a real-world case study (Pacific City) with a computational speed-up of several orders of magnitude.

Development of Efficient Techniques for the Analysis and Design of Antennas in Dual-Reflectarray Configuration

This thesis contributes to the analysis and design of printed reflectarray antennas. The main part of the work is focused on the analysis of dual offset antennas comprising two reflectarray surfaces, one of them acts as sub-reflector and the second one acts as mainreflector. These configurations introduce additional complexity in several aspects respect to conventional dual offset reflectors, however they present a lot of degrees of freedom that can be used to improve the electrical performance of the antenna. The thesis is organized in four parts: the development of an analysis technique for dualreflectarray antennas, a preliminary validation of such methodology using equivalent reflector systems as reference antennas, a more rigorous validation of the software tool by manufacturing and testing a dual-reflectarray antenna demonstrator and the practical design of dual-reflectarray systems for some applications that show the potential of these kind of configurations to scan the beam and to generate contoured beams. In the first part, a general tool has been implemented to analyze high gain antennas which are constructed of two flat reflectarray structures. The classic reflectarray analysis based on MoM under local periodicity assumption is used for both sub and main reflectarrays, taking into account the incident angle on each reflectarray element. The incident field on the main reflectarray is computed taking into account the field radiated by all the elements on the sub-reflectarray.. Two approaches have been developed, one which employs a simple approximation to reduce the computer run time, and the other which does not, but offers in many cases, improved accuracy. The approximation is based on computing the reflected field on each element on the main reflectarray only once for all the fields radiated by the sub-reflectarray elements, assuming that the response will be the same because the only difference is a small variation on the angle of incidence. This approximation is very accurate when the reflectarray elements on the main reflectarray show a relatively small sensitivity to the angle of incidence. An extension of the analysis technique has been implemented to study dual-reflectarray antennas comprising a main reflectarray printed on a parabolic surface, or in general in a curved surface. In many applications of dual-reflectarray configurations, the reflectarray elements are in the near field of the feed-horn. To consider the near field radiated by the horn, the incident field on each reflectarray element is computed using a spherical mode expansion. In this region, the angles of incidence are moderately wide, and they are considered in the analysis of the reflectarray to better calculate the actual incident field on the sub-reflectarray elements. This technique increases the accuracy for the prediction of co- and cross-polar patterns and antenna gain respect to the case of using ideal feed models. In the second part, as a preliminary validation, the proposed analysis method has been used to design a dual-reflectarray antenna that emulates previous dual-reflector antennas in Ku and W-bands including a reflectarray as subreflector. The results for the dualreflectarray antenna compare very well with those of the parabolic reflector and reflectarray subreflector; radiation patterns, antenna gain and efficiency are practically the same when the main parabolic reflector is substituted by a flat reflectarray. The results show that the gain is only reduced by a few tenths of a dB as a result of the ohmic losses in the reflectarray. The phase adjustment on two surfaces provided by the dual-reflectarray configuration can be used to improve the antenna performance in some applications requiring multiple beams, beam scanning or shaped beams. Third, a very challenging dual-reflectarray antenna demonstrator has been designed, manufactured and tested for a more rigorous validation of the analysis technique presented. The proposed antenna configuration has the feed, the sub-reflectarray and the main-reflectarray in the near field one to each other, so that the conventional far field approximations are not suitable for the analysis of such antenna. This geometry is used as benchmarking for the proposed analysis tool in very stringent conditions. Some aspects of the proposed analysis technique that allow improving the accuracy of the analysis are also discussed. These improvements include a novel method to reduce the inherent cross polarization which is introduced mainly from grounded patch arrays. It has been checked that cross polarization in offset reflectarrays can be significantly reduced by properly adjusting the patch dimensions in the reflectarray in order to produce an overall cancellation of the cross-polarization. The dimensions of the patches are adjusted in order not only to provide the required phase-distribution to shape the beam, but also to exploit the crosses by zero of the cross-polarization components. The last part of the thesis deals with direct applications of the technique described. The technique presented is directly applicable to the design of contoured beam antennas for DBS applications, where the requirements of cross-polarisation are very stringent. The beam shaping is achieved by synthesithing the phase distribution on the main reflectarray while the sub-reflectarray emulates an equivalent hyperbolic subreflector. Dual-reflectarray antennas present also the ability to scan the beam over small angles about boresight. Two possible architectures for a Ku-band antenna are also described based on a dual planar reflectarray configuration that provides electronic beam scanning in a limited angular range. In the first architecture, the beam scanning is achieved by introducing a phase-control in the elements of the sub-reflectarray and the mainreflectarray is passive. A second alternative is also studied, in which the beam scanning is produced using 1-bit control on the main reflectarray, while a passive subreflectarray is designed to provide a large focal distance within a compact configuration. The system aims to develop a solution for bi-directional satellite links for emergency communications. In both proposed architectures, the objective is to provide a compact optics and simplicity to be folded and deployed.

Integrated program debugging, verification, and optimization using abstract interpretation (and the Ciao system preprocessor)

The technique of Abstract Interpretation has allowed the development of very sophisticated global program analyses which are at the same time provably correct and practical. We present in a tutorial fashion a novel program development framework which uses abstract interpretation as a fundamental tool. The framework uses modular, incremental abstract interpretation to obtain information about the program. This information is used to validate programs, to detect bugs with respect to partial specifications written using assertions (in the program itself and/or in system libraries), to generate and simplify run-time tests, and to perform high-level program transformations such as multiple abstract specialization, parallelization, and resource usage control, all in a provably correct way. In the case of validation and debugging, the assertions can refer to a variety of program points such as procedure entry, procedure exit, points within procedures, or global computations. The system can reason with much richer information than, for example, traditional types. This includes data structure shape (including pointer sharing), bounds on data structure sizes, and other operational variable instantiation properties, as well as procedure-level properties such as determinacy, termination, nonfailure, and bounds on resource consumption (time or space cost). CiaoPP, the preprocessor of the Ciao multi-paradigm programming system, which implements the described functionality, will be used to illustrate the fundamental ideas.

Methodology for the design of offshore wind farms

Although still in an early stage, offshore wind development is now characterized by a boom process. This leads to the necessity of applying an integral management model for the design of offshore wind facilities, being the purpose of the model to achieve technical, economical and environmental viability, all within a sustainable development framework. The foregoing led to the research project exposed in this paper, consisting of drawing up an offshore wind farms methodological proposal; this methodology has a global and/or general nature or point of view whilst searching for optimization of the overall process of operations leading to the design of this type of installations and establishing collated theoretical bases for the further development of management tools. This methodological proposal follows a classical engineering thought scheme: it begins with the alternatives study, and ends with the detailed design. With this in mind, the paper includes the following sections: introduction, methodology used for the research project, conditioning factors, methodological proposal for the design of offshore wind farms, checking the methodological proposal, and conclusions

Architectural design and construction costs, tools towards territorial sustainability

This paper is presented in CIB: Management and Innovation Sustainable Built Environment 2011, as the study and analysis of the residential model of a rural area from the Iberian Peninsula, specifically applied to the case of the province of Cáceres, in the autonomous region of Extremadura, in Spain. To this end, from a database made up of building projects whose real costs are known, it is intended to establish the links of the different parameters studied through the corresponding functions of statistical analysis. One of the main objectives of this process is constituted by the possibility of establishing those design variables of higher economic importance, so as to keep an economic control of these parameters, generally geometrical and typological, from the very start of the project. And, in general, a higher optimization of resources in the construction of dwellings in the rural environment from their design is intended.

A Motor-less and Gear-less Bio-mimetic Robotic Fish Design

In this paper, we describe our current work on bio-inspired locomotion systems using a deformable structure and smart materials, concretely Shape Memory Alloys, exploring the possibility of building motor-less and gear-less robots. A swimming underwater robot has been developed whose movements are generated using such actuators, used for bending the backbone of the fish, which in turn causes a change on the curvature of the body. This paper focuses on how standard swimming patterns can be reproduced with the proposed design, using an actuation dynamics model identified in prior work.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)