Validation Of The Coronal Thick Target Source Model

We present detailed 3D modeling of a dense, coronal thick target X-ray flare using the GX Simulator tool, photospheric magnetic measurements, and microwave imaging and spectroscopy data. The developed model offers a remarkable agreement between the synthesized and observed spectra and images in both X-ray and microwave domains, which validates the entire model. The flaring loop parameters are chosen to reproduce the emission measure, temperature, and the nonthermal electron distribution at low energies derived from the X-ray spectral fit, while the remaining parameters, unconstrained by the X-ray data, are selected such as to match the microwave images and total power spectra. The modeling suggests that the accelerated electrons are trapped in the coronal part of the flaring loop, but away from where the magnetic field is minimal, and, thus, demonstrates that the data are clearly inconsistent with electron magnetic trapping in the weak diffusion regime mediated by the Coulomb collisions. Thus, the modeling supports the interpretation of the coronal thick-target sources as sites of electron acceleration in flares and supplies us with a realistic 3D model with physical parameters of the acceleration region and flaring loop.Comment: 10 pages, 5 figures, ApJ in pres

On Regularization Parameter Estimation under Covariate Shift

This paper identifies a problem with the usual procedure for L2-regularization parameter estimation in a domain adaptation setting. In such a setting, there are differences between the distributions generating the training data (source domain) and the test data (target domain). The usual cross-validation procedure requires validation data, which can not be obtained from the unlabeled target data. The problem is that if one decides to use source validation data, the regularization parameter is underestimated. One possible solution is to scale the source validation data through importance weighting, but we show that this correction is not sufficient. We conclude the paper with an empirical analysis of the effect of several importance weight estimators on the estimation of the regularization parameter.Comment: 6 pages, 2 figures, 2 tables. Accepted to ICPR 201

Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

PurposeMagnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV.MethodsThe motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique.ResultsWithout gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm.ConclusionsOur results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study

Autonomous greenhouse gas measurement system for analysis of gas migration on landfill sites

This paper describes the design, development and validation of an autonomous gas sensing platform prototype for monitoring of the greenhouse gases, methane (CH4) and carbon dioxide (CO2). The deployment undertaken for validation of the developed prototype monitored landfill gas migration to perimeter borehole wells on a landfill site. Target gas concentrations were captured via infrared gas sensors tuned for each target gas and data reported to an offsite data collection point at 12 hour intervals. This bespoke platform and the accompanying data recording and interface software provide a flexible alternative to the presently employed labor intensive, manual monitoring routines. This successful trial brought about a change in the management of the trial sites gas extraction system

Target enrichment using parallel nanoliter quantitative PCR amplification

Background: Next generation targeted resequencing is replacing Sanger sequencing at high pace in routine genetic diagnosis. The need for well validated, high quality enrichment platforms to complement the bench-top next generation sequencing devices is high. Results: We used the WaferGen Smartchip platform to perform highly parallelized PCR based target enrichment for a set of known cancer genes in a well characterized set of cancer cell lines from the NCI60 panel. Optimization of PCR assay design and cycling conditions resulted in a high enrichment efficiency. We provide proof of a high mutation rediscovery rate and have included technical replicates to enable SNP calling validation demonstrating the high reproducibility of our enrichment platform. Conclusions: Here we present our custom developed quantitative PCR based target enrichment platform. Using highly parallel nanoliter singleplex PCR reactions makes this a flexible and efficient platform. The high mutation validation rate shows this platform’s promise as a targeted resequencing method for multi-gene routine sequencing diagnostics

Benchmarking network propagation methods for disease gene identification

In-silico identification of potential target genes for disease is an essential aspect of drug target discovery. Recent studies suggest that successful targets can be found through by leveraging genetic, genomic and protein interaction information. Here, we systematically tested the ability of 12 varied algorithms, based on network propagation, to identify genes that have been targeted by any drug, on gene-disease data from 22 common non-cancerous diseases in OpenTargets. We considered two biological networks, six performance metrics and compared two types of input gene-disease association scores. The impact of the design factors in performance was quantified through additive explanatory models. Standard cross-validation led to over-optimistic performance estimates due to the presence of protein complexes. In order to obtain realistic estimates, we introduced two novel protein complex-aware cross-validation schemes. When seeding biological networks with known drug targets, machine learning and diffusion-based methods found around 2-4 true targets within the top 20 suggestions. Seeding the networks with genes associated to disease by genetics decreased performance below 1 true hit on average. The use of a larger network, although noisier, improved overall performance. We conclude that diffusion-based prioritisers and machine learning applied to diffusion-based features are suited for drug discovery in practice and improve over simpler neighbour-voting methods. We also demonstrate the large impact of choosing an adequate validation strategy and the definition of seed disease genesPeer ReviewedPostprint (published version

Does Empirical Embeddedness Matter? Methodological Issues on Agent-Based Models for Analytical Social Science

The paper deals with the use of empirical data in social science agent-based models. Agent-based models are too often viewed just as highly abstract thought experiments conducted in artificial worlds, in which the purpose is to generate and not to test theoretical hypotheses in an empirical way. On the contrary, they should be viewed as models that need to be embedded into empirical data both to allow the calibration and the validation of their findings. As a consequence, the search for strategies to find and extract data from reality, and integrate agent-based models with other traditional empirical social science methods, such as qualitative, quantitative, experimental and participatory methods, becomes a fundamental step of the modelling process. The paper argues that the characteristics of the empirical target matter. According to characteristics of the target, ABMs can be differentiated into case-based models, typifications and theoretical abstractions. These differences pose different challenges for empirical data gathering, and imply the use of different validation strategies.Agent-Based Models, Empirical Calibration and Validation, Taxanomy of Models

On Validating an Astrophysical Simulation Code

We present a case study of validating an astrophysical simulation code. Our study focuses on validating FLASH, a parallel, adaptive-mesh hydrodynamics code for studying the compressible, reactive flows found in many astrophysical environments. We describe the astrophysics problems of interest and the challenges associated with simulating these problems. We describe methodology and discuss solutions to difficulties encountered in verification and validation. We describe verification tests regularly administered to the code, present the results of new verification tests, and outline a method for testing general equations of state. We present the results of two validation tests in which we compared simulations to experimental data. The first is of a laser-driven shock propagating through a multi-layer target, a configuration subject to both Rayleigh-Taylor and Richtmyer-Meshkov instabilities. The second test is a classic Rayleigh-Taylor instability, where a heavy fluid is supported against the force of gravity by a light fluid. Our simulations of the multi-layer target experiments showed good agreement with the experimental results, but our simulations of the Rayleigh-Taylor instability did not agree well with the experimental results. We discuss our findings and present results of additional simulations undertaken to further investigate the Rayleigh-Taylor instability.Comment: 76 pages, 26 figures (3 color), Accepted for publication in the ApJ