In vitro and in vivo phasor analysis of stoichiometry and pharmacokinetics using short-lifetime near-infrared dyes and time-gated imaging
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The Minos+ experiment is an extension of the Minos experiment at a higher energy and more intense neutrino beam, with the data collection having begun in the fall of 2013. The neutrino beam is provided by the Neutrinos from the Main Injector (NuMI) beam-line at Fermi National Accelerator Laboratory (Fermilab). The detector apparatus consists of two main detectors, one underground at Fermilab and the other in Soudan, Minnesota with the purpose of studying neutrino oscillations at a base line of 735 km. The original data acquisition system has been running for several years collecting data from NuMI, but with the extended run from 2013, parts of the system needed to be replaced due to obsolescence, reliability problems, and data throughput limitations. Specifically, we have replaced the front-end readout controllers, event builder, and data acquisition computing and trigger processing farms with modern, modular and reliable devices with few single points of failure. The new system is based on gigabit Ethernet TCP/IP communication to implement the event building and concatenation of data from many front-end VME readout crates. The simplicity and partitionability of the new system greatly eases the debugging and diagnosing process. As a result, the new system improves throughput by about a factor of three compared to the old system, up to 800 megabits per second, and has proven robust and reliable in the current run.
Purpose: To establish a practical and accurate motion tracking method for the development of rigid motion correction methods in helical x-ray computed tomography (CT). Methods: A commercially available optical motion tracking system provided 6 degrees of freedom pose measurements at 60 Hz. A 4 Multiplication-Sign 4 calibration matrix was determined to convert raw pose data acquired in tracker coordinates to a fixed CT coordinate system with origin at the isocenter of the scanner. Two calibration methods, absolute orientation (AO), and a new method based on image registration (IR), were compared by means of landmark analysis and correlation coefficient in phantom images coregistered using the derived motion transformations. Results: Transformations calculated using the IR-derived calibration matrix were found to be more accurate, with positional errors less than 0.5 mm (mean RMS), and highly correlated image voxel intensities. The AO-derived calibration matrix yielded larger mean RMS positional errors ( Asymptotically-Equal-To 1.0 mm), and poorer correlation coefficients. Conclusions: The authors have demonstrated the feasibility of accurate motion tracking for retrospective motion correction in helical CT. Their new IR-based calibration method based on image registration and function minimization was simpler to perform and delivered more accurate calibration matrices. This technique is a useful tool for future work on rigid motion correction in helical CT and potentially also other imaging modalities.
The SQL Slammer Worm Infection of Davis-Besse Nuclear Power Plant 2003 Precursor Analysis Report leverages publicly available information about Davis-Besse’s 2003 cyber attack and catalogs anomalous observables for each technique employed in the attack. This analysis is based upon the methodology of the Cybersecurity for the Operational Technology Environment (CyOTE) program. On 25 January 2003, the SQL Slammer worm infected more than 90% of vulnerable hosts and crashed the internet in 10 to 15 minutes, making it one of the fastest spreading worms in history. SQL Slammer is a fileless, memory-resident worm that remotely exploits a stack-based buffer overflow vulnerability on local hosts to intensively scan and rapidly self-propagate across the internet. The worm infected approximately 300,000 unpatched hosts running Microsoft Structured Query Language (SQL) Server 2000 or Microsoft Desktop Engine (MSDE) 2000 with SQL Server Resolution Service. The SQL Slammer worm indirectly infected FirstEnergy’s Davis-Besse nuclear power plant by first infecting a consultant’s company network server and then propagating through an external misconfigured connection into Davis-Besse’s site network. The infection caused major network congestion, slow performance, data overloads, and the inability of local hosts to communicate with each other, which eventually caused a loss of availability and a loss of view when the Safety Parameter Display System (SPDS) and Plant Process Computer (PPC) crashed. At the time of the infection, the plant was already offline, the digital monitoring systems had redundant analog backups, and the plant control and safety functions were not affected, so there were no concerns of a safety breach. However, this incident resulted in many lessons learned and spawned important discussions about cybersecurity’s role in nuclear safety and electric power reliability regulation, policy, and guidance. Researchers and analysts identified 10 unique techniques utilized during the attack with a total of 640 observables using MITRE ATT&CK® for Industrial Control Systems. The CyOTE program assesses observables accompanying techniques used prior to the triggering event to identify opportunities to detect malicious activity. If observables accompanying the attack techniques are perceived and investigated prior to the triggering event, earlier comprehension of malicious activity can take place. Eight of the identified techniques used during Davis-Besse cyber attack were precursors to the triggering event. Analysis identified 596 observables associated with these precursor techniques, 428 of which were assessed to have an increased likelihood of being perceived in the 331 days preceding the triggering event. The response and comprehension time could have been reduced if the observables had been identified earlier. The information gathered in this report contributes to a library of observables tied to a repository of artifacts, data sources, and technique detection references for practitioners and developers to support the comprehension of indicators of attack. Asset owners and operators can use these products if they experience similar observables or to prepare for comparable scenarios.
A hierarchy of statistics of increasing sophistication and accuracy is proposed to exploit an interesting and fundamental arithmetic structure in the photon bunching noise of incoherent light of large photon occupation number, with the purpose of suppressing the noise and rendering a more reliable and unbiased measurement of the light intensity. The method does not require any new hardware, rather it operates at the software level with the help of high-precision computers to reprocess the intensity time series of the incident light to create a new series with smaller bunching noise coherence length. The ultimate accuracy improvement of this method of flux measurement is limited by the timing resolution of the detector and the photon occupation number of the beam (the higher the photon number the better the performance). The principal application is accuracy improvement in the signal-limited bolometric flux measurement of a radio source.
Star-forming galaxies have been predicted to contribute considerably to the diffuse gamma-ray background as they are guaranteed reservoirs of cosmic rays. Assuming that the hadronic interactions responsible for high-energy gamma rays also produce high-energy neutrinos and that O(100) PeV cosmic rays can be produced and confined in starburst galaxies, we here discuss the possibility that star-forming galaxies are also the main sources of the high-energy neutrinos observed by the IceCube experiment. First, we compute the diffuse gamma-ray background from star-forming galaxies, adopting the latest Herschel PEP/HerMES luminosity function and relying on the correlation between the gamma-ray and infrared luminosities reported by Fermi observations. Then we derive the expected intensity of the diffuse high-energy neutrinos from star-forming galaxies including normal and starburst galaxies. Our results indicate that starbursts, including those with active galactic nuclei and galaxy mergers, could be the main sources of the high-energy neutrinos observed by the IceCube experiment. We find that assuming a cosmic-ray spectral index of 2.1–2.2 for all starburst-like galaxies, our predictions can be consistent with both the Fermi and IceCube data, but larger indices readily fail to explain the observed diffuse neutrino flux. Taking the starburst high-energy spectral index as free parameter, and extrapolating from GeV to PeV energies, we find that the spectra harder than E{sup -2.15} are likely to be excluded by the IceCube data, which can be more constraining than the Fermi data for this population.
Photoionization of Cs (6p {sup 2}P{sub 3/2}) atoms during the operation of a Cs D{sub 2} line (852.1 nm: 6p {sup 2}P{sub 3/2}{yields}6s {sup 2}S{sub 1/2}) laser, pumped by free{yields}free transitions of thermal Cs-Ar ground state pairs, has been investigated experimentally and computationally. Photoexcitation of Cs vapor/Ar mixtures through the blue satellite of the D{sub 2} transition (peaking at 836.7 nm) selectively populates the {sup 2}P{sub 3/2} upper laser level by the dissociation of the CsAr excited complex. Comparison of laser output energy data, for instantaneous pump powers up to 3 MW, with the predictions of a numerical model sets an upper bound of 8 Multiplication-Sign 10{sup -26} cm{sup 4} W{sup -1} on the Cs (6p {sup 2}P{sub 3/2}) two photon ionization cross-section at 836.7 nm which corresponds to a single photon cross-section of 2.4 Multiplication-Sign 10{sup -19} cm{sup 2} for a peak pump intensity of 3 MW cm{sup -2}.
We present massively parallel high energy electromagnetic particle transportation through a finely segmented detector on a Graphics Processing Unit (GPU). Simulating events of energetic particle decay in a general-purpose high energy physics (HEP) detector requires intensive computing resources, due to the complexity of the geometry as well as physics processes applied to particles copiously produced by primary collisions and secondary interactions. The recent advent of hardware architectures of many-core or accelerated processors provides the variety of concurrent programming models applicable not only for the high performance parallel computing, but also for the conventional computing intensive application such as the HEP detector simulation. The components of our prototype are a transportation process under a non-uniform magnetic field, geometry navigation with a set of solid shapes and materials, electromagnetic physics processes for electrons and photons, and an interface to a framework that dispatches bundles of tracks in a highly vectorized manner optimizing for spatial locality and throughput. Core algorithms and methods are excerpted from the Geant4 toolkit, and are modified and optimized for the GPU application. Program kernels written in C/C++ are designed to be compatible with CUDA and OpenCL and with the aim to be generic enough for easy porting to future programming models and hardware architectures. To improve throughput by overlapping data transfers with kernel execution, multiple CUDA streams are used. Issues with floating point accuracy, random numbers generation, data structure, kernel divergences and register spills are also considered. Performance evaluation for the relative speedup compared to the corresponding sequential execution on CPU is presented as well.
Purpose: Multileaf collimator (MLC) leaf sequencing is performed via commercial black-box implementations, on which a user has limited to no access. We have developed an explicit, generic MLC sequencing model to serve as a tool for future investigations of fluence map optimization, fluence delivery optimization, and rotational collimator delivery methods. Methods: We have developed a novel, comprehensive model to effectively account for a variety of transmission and penumbra effects previously treated on an ad hoc basis in the literature. As the model is capable of quantifying a variety of effects, we utilize the asymmetric leakage intensity across each leaf to deliver fluence maps with pixel size smaller than the narrowest leaf width. Developed using linear programming and mixed integer programming formulations, the model is implemented using state of the art open-source solvers. To demonstrate the versatility of the algorithm, a graphical user interface (GUI) was developed in MATLAB capable of accepting custom leaf specifications and transmission parameters. As a preliminary proof-ofconcept, we have sequenced the leaves of a Varian 120 Leaf Millennium MLC for five prostate cancer patient fields and one head and neck field. Predetermined fluence maps have been processed by data smoothing methods to obtain pixel sizes of 2.5 cm{sup 2}. The quality of output was analyzed using computer simulations. Results: For the prostate fields, an average root mean squared error (RMSE) of 0.82 and gamma (0.5mm/0.5%) of 91.4% were observed compared to RMSE and gamma (0.5mm/0.5%) values of 7.04 and 34.0% when the leakage considerations were omitted. Similar results were observed for the head and neck case. Conclusion: A model to sequence MLC leaves to optimality has been proposed. Future work will involve extensive testing and evaluation of the method on clinical MLCs and comparison with black-box leaf sequencing algorithms currently used by commercial treatment planning systems.
This High Performance Data Facility (HPDF) Project is creating a new scientific user facility to provide advanced infrastructure for data-intensive science, supporting the DOE’s Office of Science (SC) community. HPDF’s mission is to enable and accelerate scientific discovery by delivering state-of-the-art data management infrastructure, capabilities, and tools. This meta-analysis examines the needs of the breadth of the SC community, captured in publicly available community reports or mission documents. The meta-analysis identifies and provides initial characterization of fifteen core requirements for the HPDF Project team to consider during the conceptual design phase. The fifteen requirements illustrate how scientific work among SC communities requires modern, seamless user experiences across the ASCR Ecosystem to advance the use of large volumes of heterogeneous data. The scientific community requires support for the missing middle of compute between local and HPC to interactively and collaboratively use growing datasets. Data producers and end users will benefit from enhanced data catalogs and portals that improve data access through advanced search of well curated data. The fifteen requirements are examined here organized across five themes for discussion. Examples in each theme illustrate the array of scientific needs that convey the important role that the fully realized and operational High Performance Data Facility will be able to play as an integral part of the evolving ASCR Ecosystem. Our amalgamated data tables from ESnet reports demonstrate ranges to the volumes of data HPDF must be concerned with, but limitations are inherent to this meta-analysis (see Key Challenges & Limitations). Feedback and validation of these requirements along with additional details and emergent community requirements will be gathered through user research and design activities.
Process monitoring and control requires detection of structural changes in a data stream in real time. This paper introduces an efficient sequential Monte Carlo algorithm designed for learning unknown changepoints in continuous time. The method is intuitively simple: new changepoints for the latest window of data are proposed by conditioning only on data observed since the most recent estimated changepoint, as these observations carry most of the information about the current state of the process. The proposed method shows improved performance over the current state of the art. Another advantage of the proposed algorithm is that it can be made adaptive, varying the number of particles according to the apparent local complexity of the target changepoint probability distribution. This saves valuable computing time when changes in the changepoint distribution are negligible, and enables re-balancing of the importance weights of existing particles when a significant change in the target distribution is encountered. The plain and adaptive versions of the method are illustrated using the canonical continuous time changepoint problem of inferring the intensity of an inhomogeneous Poisson process, although the method is generally applicable to any changepoint problem. Performance is demonstrated using both conjugate and non-conjugate Bayesian models for the intensity. Lastly, appendices to the article are available online, illustrating the method on other models and applications.
With the increase of the scale and intensity of the parallel I/O workloads generated by those scientific applications running on high performance computing facilities, understanding the I/O dynamics, especially the root cause of the I/O performance variability and degradation in HPC environment, have become extremely critical to the HPC community. In this paper, we run extensive I/O measuring tests on a production leadership-class storage system to capture the performance variabilities of large-scale parallel I/O. Analyzing these results and its statistic correlation revealed some valuable insights into the characteristics of the storage system and the root cause of I/O performance variability. Further, we leverage these findings and propose an I/O middleware design refactoring which can improve the performance of the parallel I/O by optimizing the data striping and placement. Our preliminary evaluation results demonstrate the proposed approach can reduce the average per-process write latency by at least 80% and the maximum per-process write latency by at least 20%.
Plasma physics simulations are vital for a host of Sandia mission concerns, for fundamental science, and for clean energy in the form of fusion power. Sandia's most mature plasma physics simulation capabilities come in the form of particle-in-cell (PIC) models and magnetohydrodynamics (MHD) models. MHD models for a plasma work well in denser plasma regimes when there is enough material that the plasma approximates a fluid. PIC models, on the other hand, work well in lower-density regimes, in which there is not too much to simulate; error in PIC scales as the square root of the number of particles, making high-accuracy simulations expensive. Real-world applications, however, almost always involve a transition region between the high-density regimes where MHD is appropriate, and the low-density regimes for PIC. In such a transition region, a direct discretization of Vlasov is appropriate. Such discretizations come with their own computational costs, however; the phase-space mesh for Vlasov can involve up to six dimensions (seven if time is included), and to apply appropriate homogeneous boundary conditions in velocity space requires meshing a substantial padding region to ensure that the distribution remains sufficiently close to zero at the velocity boundaries. Moreover, for collisional plasmas, the right-hand side of the Vlasov equation is a collision operator, which is non-local in velocity space, and which may dominate the cost of the Vlasov solver. The present LDRD project endeavors to develop modern, foundational tools for the development of continuum-kinetic Vlasov solvers, using the discontinuous Petrov-Galerkin (DPG) methodology, for discretization of Vlasov, and machine-learning (ML) models to enable efficient evaluation of collision operators. DPG affords several key advantages. First, it has a built-in, robust error indicator, allowing us to adapt the mesh in a very natural way, enabling a coarse velocity-space mesh near the homogeneous boundaries, and a fine mesh where the solution has fine features. Second, it is an inherently high-order, high-intensity method, requiring extra local computations to determine so-called optimal test functions, which makes it particularly suited to modern hardware in which floating-point throughput is increasing at a faster rate than memory bandwidth. Finally, DPG is a residual-minimizing method, which enables high-accuracy computation: in typical cases, the method delivers something very close to the $L^2$ projection of the exact solution. Meanwhile, the ML-based collision model we adopt affords a cost structure that scales as the square root of a standard direct evaluation. Moreover, we design our model to conserve mass, momentum, and energy by construction, and our approach to training is highly flexible, in that it can incorporate not only synthetic data from direct-simulation Monte Carlo (DSMC) codes, but also experimental data. We have developed two DPG formulations for Vlasov-Poisson: a time-marching, backward-Euler discretization and a space-time discretization. We have conducted a number of numerical experiments to verify the approach in a 1D1V setting. In this report, we detail these formulations and experiments. We also summarize some new theoretical results developed as part of this project (published as papers previously): some new analysis of DPG for the convection-reaction problem (of which the Vlasov equation is an instance), a new exponential integrator for DPG, and some numerical exploration of various DPG-based time-marching approaches to the heat equation. As part of this work, we have contributed extensively to the Camellia open-source library; we also describe the new capabilities and their usage. We have also developed a well-documented methodology for single-species collision operators, which we applied to argon and demonstrated with numerical experiments. We summarize those results here, as well as describing at a high level a design extending the methodology to multi-species operators. We have released a new open-source library, MLC, under a BSD license; we include a summary of its capabilities as well.
Surrogate models are increasingly required for applications in which first-principles simulation models are prohibitively expensive to employ for uncertainty analysis, design, or control. They can also be used to approximate models whose discontinuous derivatives preclude the use of gradient-based optimization or data assimilation algorithms. We consider the problem of inferring the 2D location and intensity of a radiation source in an urban environment using a ray-tracing model based on Boltzmann transport theory. Whereas the code implementing this model is relatively efficient, extension to 3D Monte Carlo transport simulations precludes subsequent Bayesian inference to infer source locations, which typically requires thousands to millions of simulations. Additionally, the resulting likelihood exhibits discontinuous derivatives due to the presence of buildings. To address these issues, we discuss the construction of surrogate models for optimization, Bayesian inference, and uncertainty propagation. Specifically, we consider surrogate models based on Legendre polynomials, multivariate adaptive regression splines, radial basis functions, Gaussian processes, and neural networks. We detail strategies for computing training points and discuss the merits and deficits of each method.
Abstract. Future changes in Earth system state will impact agricultural yields and, through these changed yields, can have profound impacts on the global economy. Global gridded crop models estimate the influence of these Earth system changes on future crop yields but are often too computationally intensive to dynamically couple into global multi-sector economic models, such as the Global Change Assessment Model (GCAM) and other similar-in-scale models. Yet, generalizing a faster site-specific crop model's results to be used globally will introduce inaccuracies, and the question of which model to use is unclear given the wide variation in yield response across crop models. To examine the feedback loop among socioeconomics, Earth system changes, and crop yield changes, rapidly generated yield responses with some quantification of crop response uncertainty are desirable. The Persephone v1.0 response functions presented in this work are based on the Agricultural Model Intercomparison and Improvement Project (AgMIP) Coordinated Climate-Crop Modeling Project (C3MP) sensitivity test data set and are focused on providing GCAM and similar models with a tractable number of rapid to evaluate dynamic yield response functions corresponding to a range of the yield response sensitivities seen in the C3MP data set. With the Persephone response functions, a new variety of agricultural impact experiments will be open to GCAM and other economic models: for example, examining the economic impacts of a multi-year drought in a key agricultural region and how economic changes in response to the drought can, in turn, impact the drought.
Methods based on quantum mechanics equations have been developed since the 1930's with the purpose of accurately studying the electronic structure of molecules. However, it is only during the last two decades that intense development of new computational algorithms has opened the possibility of performing accurate simulations of challenging molecular processes with high-order many-body methods. A wealth of evidence indicates that the proper inclusion of instantaneous interactions between electrons (or the so-called electron correlation effects) is indispensable for the accurate characterization of chemical reactivity, molecular properties, and interactions of light with matter. The availability of reliable methods for benchmarking of medium-size molecular systems provides also a unique chance to propagate high-level accuracy across spatial scales through the multiscale methodologies. Some of these methods have potential to utilize computational resources in an effi*cient way since they are characterized by high numerical complexity and appropriate level of data granularity, which can be effi*ciently distributed over multi-processor architectures. The broad spectrum of coupled cluster (CC) methods falls into this class of methodologies. Several recent CC implementations clearly demonstrated the scalability of CC formalisms on architectures composed of hundreds thousand computational cores. In this context NWChem provides a collection of Tensor Contraction Engine (TCE) generated parallel implementations of various coupled cluster methods capable of taking advantage of many thousand of cores on leadership class parallel architectures.
Reactor dynamics simulations provide essential insights into the time-dependent behavior of nuclear reactors under various operating conditions. However, high-fidelity simulations can be computationally intensive, requiring significant computational resources. Here, to address this challenge, this study employs a differentiable hybrid model that utilizes neural networks as a corrector to enhance the performance of a low-fidelity simulation, aligning its predictions with those of a high-fidelity simulation. Low-fidelity and high-fidelity simulations were obtained by adjusting the mesh size in the System Dynamics Analysis Tool. The differentiable hybrid model was trained in two approaches: time-step-wise and sequence-wise. It was then applied to simulate various transients in a molten salt reactor. Its performance was evaluated by comparing its responses to transients against those of the high-fidelity simulation. An additional approach was performed using a data-driven model to correct the low-fidelity simulation. In comparison, the differentiable hybrid model showed significant improvements in transient prediction, effectively addressing the limitations of the low-fidelity simulations. The results highlighted the robustness of the differentiable hybrid model in both training approaches. It delivered simulations that were at least 3.8 times faster than high-fidelity models. In the time-step-wise approach, it achieved at least a 39% improvement in accuracy. In the sequence-wise approach, it showed at least an 81% accuracy improvement over the full transient. This approach offers a promising path for improving computational efficiency without compromising accuracy in nuclear reactor simulations, making it suitable for real-time digital twin applications.
Due to its nonlinear nature, the supply fan at air handling units with the controller tuned at the design condition tends to be aggressive and oscillate under partial load conditions. Here, the objective of this paper is to develop and validate a gain scheduling control strategy to improve its nonlinear control performance. First, a control-oriented model, which does not require numerous physical parameters and extensive test data, is developed to study the nonlinearity of the fan system. Based on the theoretical model and experimental verifications, the issue of an aggressive response with a conventional fixed-gain controller is caused by the fact that the system gain is proportional to the ratio of the duct static pressure to the fan speed. To address the issue, a scheduling function of the measurable duct static pressure and fan speed is proposed to be included in the conventional fixed-gain controller to compensate for the fan system gain variation. The gain scheduling control strategy is found to approximately maintain the identical control performance under all operation conditions. Most importantly, the gain scheduling control strategy can be readily implemented without intensive computation and additional measurements, showing a promising potential in industrial applications.