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At least 1,459 records · Page 81

Nanopores and nucleic acids: prospects for ultrarapid sequencing

DNA and RNA molecules can be detected as they are driven through a nanopore by an applied electric field at rates ranging from several hundred microseconds to a few milliseconds per molecule. The nanopore can rapidly discriminate between pyrimidine and purine segments along a single-stranded nucleic acid molecule. Nanopore detection and characterization of single molecules represents a new method for directly reading information encoded in linear polymers. If single-nucleotide resolution can be achieved, it is possible that nucleic acid sequences can be determined at rates exceeding a thousand bases per second.

Review↗

SU-E-J-224: Using UTE and T1 Weighted Spin Echo Pulse Sequences for MR-Only Treatment Planning; Phantom Study

Purpose: Investigating a new approach in MRI based treatment planning using the combination of (Ultrashort Echo Time) UTE and T1 weighted spin echo pulse sequences to delineate air, bone and water (soft tissues) in generating pseudo CT images comparable with CT. Methods: A gel phantom containing chicken bones, ping pang balls filled with distilled water and air bubbles, was made. It scanned with MRI using UTE and 2D T1W SE pulse sequences with (in plane resolution= 0.53mm, slice thickness= 2 mm) and CT with (in plane resolution= 0.5 mm and slice thickness= 0.75mm) as a ground truth for geometrical accuracy. The UTE and T1W SE images were registered with CT using mutual information registration algorithm provided by Philips Pinnacle treatment planning system. The phantom boundaries were detected using Canny edge detection algorithm for CT, and MR images. The bone, air bubbles and water in ping pong balls were segmented from CT images using threshold 300HU, - 950HU and 0HU, respectively. These tissue inserts were automatically segmented from combined UTE and T1W SE images using edge detection and relative intensity histograms of the phantom. The obtained segmentations of air, bone and water inserts were evaluated with those obtained from CT. Results: Bone and air can be clearly differentiated in UTE images comparable to CT. Combining UTE and T1W SE images successfully segmented the air, bone and water. The maximum segmentation differences from combine MRI images (UTE and T1W SE) and CT are within 1.3 mm, 1.1mm for bone, air, respectively. The geometric distortion of UTE sequence is small less than 1 pixel (0.53 mm) of MR image resolution. Conclusion: Our approach indicates that MRI can be used solely for treatment planning and its quality is comparable with CT.

60 APPLIED LIFE SCIENCES↗

Advances in molecular serotyping and subtyping of Escherichia coli

Escherichia coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for E. coli , which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS) of E. coli is replacing established subtyping methods such as pulsedfield gel electrophoresis, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. Furthermore, a variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.

59 BASIC BIOLOGICAL SCIENCES↗

TreeSAPP: the Tree-based Sensitive and Accurate Phylogenetic Profiler

Microbial communities drive matter and energy transformations integral to global biogeochemical cycles, yet many taxonomic groups facilitating these processes remain poorly represented in biological sequence databases. Due to this missing information, taxonomic assignment of sequences from environmental genomes remains inaccurate. We present the Tree-based Sensitive and Accurate Phylogenetic Profiler (TreeSAPP) software for functionally and taxonomically classifying genes, reactions and pathways from genomes of cultivated and uncultivated microorganisms using reference packages representing coding sequences mediating multiple globally relevant biogeochemical cycles. TreeSAPP uses linear regression of evolutionary distance on taxonomic rank to improve classifications, assigning both closely related and divergent query sequences at the appropriate taxonomic rank. TreeSAPP is able to provide quantitative functional and taxonomic classifications for both assembled and unassembled sequences and files supporting interactive tree of life visualizations.

54 ENVIRONMENTAL SCIENCES↗

SU-F-J-103: Assessment of Liver Tumor Contrast for Radiation Therapy: Inter-Patient and Inter-Sequence Variability

Purpose: To determine the variation in tumor contrast between different MRI sequences and between patients for the purpose of MRI-based treatment planning. Methods: Multiple MRI scans of 11 patients with cancer(s) in the liver were included in this IRB-approved study. Imaging sequences consisted of T1W MRI, Contrast-Enhanced T1W MRI, T2W MRI, and T2*/T1W MRI. MRI images were acquired on a 1.5T GE Signa scanner with a four-channel torso coil. We calculated the tumor-to-tissue contrast to noise ratio (CNR) for each MR sequence by contouring the tumor and a region of interest (ROI) in a homogeneous region of the liver using the Eclipse treatment planning software. CNR was calculated (I-Tum-I-ROI)/SD-ROI, where I-Tum and I-ROI are the mean values of the tumor and the ROI respectively, and SD-ROI is the standard deviation of the ROI. The same tumor and ROI structures were used in all measurements for different MR sequences. Inter-patient Coefficient of variation (CV), and inter-sequence CV was determined. In addition, mean and standard deviation of CNR were calculated and compared between different MR sequences. Results: Our preliminary results showed large inter-patient CV (range: 37.7% to 88%) and inter-sequence CV (range 5.3% to 104.9%) of liver tumor CNR, indicating great variations in tumor CNR between MR sequences and between patients. Tumor CNR was found to be largest in CE-T1W (8.5±7.5), followed by T2W (4.2±2.4), T1W (3.4±2.2), and T2*/T1W (1.7±0.6) MR scans. The inter-patient CV of tumor CNR was also the largest in CE-T1W (88%), followed by T1W (64.3%), T1W (56.2%), and T2*/T1W (37.7) MR scans. Conclusion: Large inter-sequence and inter-patient variations were observed in liver tumor CNR. CE-T1W MR images on average provided the best tumor CNR. Efforts are needed to optimize tumor contrast and its consistency for MRI-based treatment planning of cancer in the liver. This project is supported by NIH grant: 1R21CA165384.

60 APPLIED LIFE SCIENCES↗

Numerical methods for high-dimensional probability density function equations

In this paper we address the problem of computing the numerical solution to kinetic partial differential equations involving many phase variables. These types of equations arise naturally in many different areas of mathematical physics, e.g., in particle systems (Liouville and Boltzmann equations), stochastic dynamical systems (Fokker–Planck and Dostupov–Pugachev equations), random wave theory (Malakhov–Saichev equations) and coarse-grained stochastic systems (Mori–Zwanzig equations). We propose three different classes of new algorithms addressing high-dimensionality: The first one is based on separated series expansions resulting in a sequence of low-dimensional problems that can be solved recursively and in parallel by using alternating direction methods. The second class of algorithms relies on truncation of interaction in low-orders that resembles the Bogoliubov–Born–Green–Kirkwood–Yvon (BBGKY) framework of kinetic gas theory and it yields a hierarchy of coupled probability density function equations. The third class of algorithms is based on high-dimensional model representations, e.g., the ANOVA method and probabilistic collocation methods. A common feature of all these approaches is that they are reducible to the problem of computing the solution to high-dimensional equations via a sequence of low-dimensional problems. The effectiveness of the new algorithms is demonstrated in numerical examples involving nonlinear stochastic dynamical systems and partial differential equations, with up to 120 variables.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Comparison of the Effects of Velocity and Range Triggers on Trajectory Dispersions for the Mars 2020 Mission

Mars 2020, the next planned U.S. rover mission to land on Mars, is based on the design of the successful 2012 Mars Science Laboratory (MSL) mission. Mars 2020 retains most of the entry, descent, and landing (EDL) sequences of MSL, including the closed-loop entry guidance scheme based on the Apollo guidance algorithm. However, unlike MSL, Mars 2020 will trigger the parachute deployment and descent sequence on range trigger rather than the previously used velocity trigger. This difference will greatly reduce the landing ellipse sizes. Additionally, the relative contribution of each models to the total ellipse sizes have changed greatly due to the switch to range trigger. This paper considers the effect on trajectory dispersions due to changing the trigger schemes and the contributions of these various models to trajectory and EDL performance.

Dutta, Soumyo↗

Real Time Metrics and Analysis of Integrated Arrival, Departure, and Surface Operations

To address the Integrated Arrival, Departure, and Surface (IADS) challenge, NASA is developing and demonstrating trajectory-based departure automation under a collaborative effort with the FAA and industry known Airspace Technology Demonstration 2 (ATD-2). ATD-2 builds upon and integrates previous NASA research capabilities that include the Spot and Runway Departure Advisor (SARDA), the Precision Departure Release Capability (PDRC), and the Terminal Sequencing and Spacing (TSAS) capability. As trajectory-based departure scheduling and collaborative decision making tools are introduced in order to reduce delays and uncertainties in taxi and climb operations across the National Airspace System, users of the tools across a number of roles benefit from a real time system that enables common situational awareness. A real time dashboard was developed to inform and present users notifications and integrated information regarding airport surface operations. The dashboard is a supplement to capabilities and tools that incorporate arrival, departure, and surface air-traffic operations concepts in a NextGen environment. In addition to shared situational awareness, the dashboard offers the ability to compute real time metrics and analysis to inform users about capacity, predictability, and efficiency of the system as a whole. This paper describes the architecture of the real time dashboard as well as an initial proposed set of metrics. The potential impact of the real time dashboard is studied at the site identified for initial deployment and demonstration in 2017: Charlotte-Douglas International Airport (CLT). The architecture of implementing such a tool as well as potential uses are presented for operations at CLT. Metrics computed in real time illustrate the opportunity to provide common situational awareness and inform users of system delay, throughput, taxi time, and airport capacity. In addition, common awareness of delays and the impact of takeoff and departure restrictions stemming from traffic flow management initiatives are explored. The potential of the real time tool to inform users of the predictability and efficiency of using a trajectory-based departure scheduling system is also discussed.

integrated arrival departure surface operations↗

Microbiome-wide association studies link dynamic microbial consortia to disease

Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.

Gilbert, Jack A.↗

Divergent viral phosphodiesterases for immune signaling evasion

Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase (PDE)-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. Here, we use a canonical 2H PDE (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments reveal remarkable substrate specificity of these PDEs that corresponds to variations in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host nucleotide signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.

CBASS↗

TH-EF-BRA-06: A Novel Retrospective 3D K-Space Sorting 4D-MRI Technique Using a Radial K-Space Acquisition MRI Sequence

Purpose: Current retrospective 4D-MRI provides superior tumor-to-tissue contrast and accurate respiratory motion information for radiotherapy motion management. The developed 4D-MRI techniques based on 2D-MRI image sorting require a high frame-rate of the MR sequences. However, several MRI sequences provide excellent image quality but have low frame-rate. This study aims at developing a novel retrospective 3D k-space sorting 4D-MRI technique using radial k-space acquisition MRI sequences to improve 4D-MRI image quality and temporal-resolution for imaging irregular organ/tumor respiratory motion. Methods: The method is based on a RF-spoiled, steady-state, gradient-recalled sequence with minimal echo time. A 3D radial k-space data acquisition trajectory was used for sampling the datasets. Each radial spoke readout data line starts from the 3D center of Field-of-View. Respiratory signal can be extracted from the k-space center data point of each spoke. The spoke data was sorted based on its self-synchronized respiratory signal using phase sorting. Subsequently, 3D reconstruction was conducted to generate the time-resolved 4D-MRI images. As a feasibility study, this technique was implemented on a digital human phantom XCAT. The respiratory motion was controlled by an irregular motion profile. To validate using k-space center data as a respiratory surrogate, we compared it with the XCAT input controlling breathing profile. Tumor motion trajectories measured on reconstructed 4D-MRI were compared to the average input trajectory. The mean absolute amplitude difference (D) was calculated. Results: The signal extracted from k-space center data matches well with the input controlling respiratory profile of XCAT. The relative amplitude error was 8.6% and the relative phase error was 3.5%. XCAT 4D-MRI demonstrated a clear motion pattern with little serrated artifacts. D of tumor trajectories was 0.21mm, 0.23mm and 0.23mm in SI, AP and ML directions, respectively. Conclusion: A novel retrospective 3D k-space sorting 4D-MRI technique has been developed and evaluated on human digital phantom. NIH (1R21CA165384-01A1)

60 APPLIED LIFE SCIENCES↗

Breaking the curse of dimensionality to identify causal variants in Breeding 4

In the past, plant breeding has undergone three major transformations and is currently transitioning to a new technological phase, Breeding 4. This phase is characterized by the development of methods for biological design of plant varieties, including transformation and gene editing techniques directed toward causal loci. The application of such technologies will require to reliably estimate the effect of loci in plant genomes by avoiding the situation where the number of loci assayed ($p$) surpasses the number of plant genotypes (n). Here, we discuss approaches to avoid this curse of dimensionality ($n\ll p$), which will involve analyzing intermediate phenotypes such as molecular traits and component traits related to plant morphology or physiology. Because these approaches will rely on novel data types such as DNA sequences and high-throughput phenotyping images, Breeding 4 will call for analyses that are complementary to traditional quantitative genetic studies, being based on machine learning techniques which make efficient use of sequence and image data. In this article, we will present some of these techniques and their application for prioritizing causal loci and developing improved varieties in Breeding 4.

59 BASIC BIOLOGICAL SCIENCES↗

Modelica-json: Transforming energy models to digitize the control delivery process

Building simulation models are typically not used to generate the documentation required for bidding and project delivery of commercial building systems, or for their semantic modeling and commissioning. This paper presents a software tool that aids in digitizing the control delivery process, spanning simulation during design to implementation and formal verification during commissioning. The tool can generate from Modelica models digital documentation of control sequences. This digital documentation, along with other project drawings and specifications can be used for project bidding. It can also be used for implementation of control sequences through machineto-machine translation to commercial legacy control products, for which we are currently developing the proposed ASHRAE Standard 231P based on the presented work. Moreover, as-installed control sequences can be formally verified against the design specification, and a semantic model in Brick can be exported to aid in configuration of building analytics and fault detection. The paper presents what we believe is the first translation of a Modelica-implemented control sequence to a native implementation on a commercial control platform, using the webCTRL product line from Automated Logic. The paper also shows how a webCTRL implementation can be formally verified against its Modelica specification. These use cases have all been demonstrated with a prototype implementation that is now being further developed.

Wetter, Michael↗

Operational Impact of the Baseline Integrated Arrival, Departure and Surface System Field Demonstration

To address the Integrated Arrival, Departure, and Surface (IADS) challenge, NASA is developing and demonstrating trajectory-based departure automation under a collaborative effort with the FAA (Federal Aviation Administration) and industry known Airspace Technology Demonstration 2 (ATD-2). ATD-2 builds upon and integrates previous NASA research capabilities that include the Spot and Runway Departure Advisor (SARDA), the Precision Departure Release Capability (PDRC), and the Terminal Sequencing and Spacing (TSAS) capability. As trajectory-based departure scheduling and collaborative decision making tools are introduced in order to reduce delays and uncertainties in taxi and climb operations across the National Airspace System, users of the tools across a number of roles benefit from a real time system that enables common situational awareness. A real time dashboard was developed to inform and present users notifications and integrated information regarding airport surface operations. The dashboard is a supplement to capabilities and tools that incorporate arrival, departure, and surface air-traffic operations concepts in a NextGen environment. In addition to shared situational awareness, the dashboard offers the ability to compute real time metrics and analysis to inform users about capacity, predictability, and efficiency of the system as a whole. This paper describes the architecture of the real time dashboard as well as an initial proposed set of metrics. The potential impact of the real time dashboard is studied at the site identified for initial deployment and demonstration in 2017: Charlotte-Douglas International Airport (CLT). The architecture of implementing such a tool as well as potential uses are presented for operations at CLT. Metrics computed in real time illustrate the opportunity to provide common situational awareness and inform users of system delay, throughput, taxi time, and airport capacity. In addition, common awareness of delays and the impact of takeoff and departure restrictions stemming from traffic flow management initiatives are explored. The potential of the real time tool to inform users of the predictability and efficiency of using a trajectory-based departure scheduling system is also discussed.

air traffic optimization↗

A packet-based concept for spacecraft command planning

The current generation of spacecraft being developed and operated by the Applied Physics Laboratory provides users with access to a broad spectrum of scientific instruments on maneuverable platforms that can be oriented for observation of both moving and stationary targets of interest. The capability of these increasingly complex spacecraft to perform data collection operations is approaching one observation per orbit. To enable both rapid configuration and generation of complex spacecraft command sequences, as well as reusability of command sequences among data collection operations, a packet-based concept for spacecraft command planning has been developed. The configuration of the spacecraft for any operation is designed using 'packets' where a packet represents a set of commands that is reusable. The packets can be combined in varying levels of functionality, and in varying time relationships, to create an observation timeline. At the lowest packet level are primitives. Primitives relate the details of command generation for a particular spacecraft to a 'message template.' Thus the packet concept itself is reusable from one spacecraft to the next.

Barnes, Valerie B.↗

Working fluid selection for space-based two-phase heat transport systems

The working fluid for externally-mounted, space-based two-phase heat transport systems is considered. A sequence of screening criteria involving freezing and critical point temperatures and latent heat of vaporization and vapor density are applied to a data base of 860 fluids. The thermal performance of the 52 fluids which pass this preliminary screening are then ranked according to their impact on the weight of a reference system. Upon considering other nonthermal criteria (flammability, toxicity, and chemical stability) a final set of 10 preferred fluids is obtained. The effects of variations in system parameters is investigated for these 10 fluids by means of a factorial design.

Mclinden, Mark O.↗

Risk-based Prioritization of Facility Decommissioning and Environmental Restoration Projects in the National Nuclear Legacy Liabilities Program at the Chalk River Laboratory - 13564

Chalk River Laboratory (CRL), located in Ontario Canada, has a large number of remediation projects currently in the Nuclear Legacy Liabilities Program (NLLP), including hundreds of facility decommissioning projects and over one hundred environmental remediation projects, all to be executed over the next 70 years. Atomic Energy of Canada Limited (AECL) utilized WorleyParsons to prioritize the NLLP projects at the CRL through a risk-based prioritization and ranking process, using the WorleyParsons Sequencing Unit Prioritization and Estimating Risk Model (SUPERmodel). The prioritization project made use of the SUPERmodel which has been previously used for other large-scale site prioritization and sequencing of facilities at nuclear laboratories in the United States. The process included development and vetting of risk parameter matrices as well as confirmation/validation of project risks. Detailed sensitivity studies were also conducted to understand the impacts that risk parameter weighting and scoring had on prioritization. The repeatable prioritization process yielded an objective, risk-based and technically defendable process for prioritization that gained concurrence from all stakeholders, including Natural Resources Canada (NRCan) who is responsible for the oversight of the NLLP. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Environmental Risk Evaluation System – An Approach to Ranking Risk of Ocean Energy Development on Coastal and Estuarine Environments

Deployment and operation of ocean energy devices does not represent the first foray into industrialization of the oceans; shipping, nearshore development, waste disposal, subsea mining, oil and gas extraction, and large-scale commercial fishing all coexist in various states of equilibrium with the marine environment. In most cases these industries were developed without a clear understanding of the likely outcomes of large-scale development. In virtually every country where the harvest of ocean energy is emerging, regulators and stakeholders require that the industry examine potential effects of devices, minimize the footprint of effects, and provide management measures that either avoid the impacts or mitigate to further reduce the residual impacts. The ERES analysis is based on scenarios that are consistent with sequences of events that lead to adverse impacts, distinguishing between episodic, intermittent, and chronic risks. In the context of ocean energy development, an episodic scenario might involve the exceedingly rare but potentially devastating event of an oil spill from vessels caused by the presence of the device, while vulnerable receptors are present; understanding the risk of such a scenario involves determining the probability of the occurrence by examining factors such as the petroleum content of ocean energy devices, the vessel traffic volume and the proximity of shipping lanes to the ocean energy devices, the reliability of the control measures to avoid an episodic event, and the likely presence of seabirds, marine mammals, or fish that may be affected by oil. In contrast, chronic risk scenarios involve events or circumstances that are continuous, so that risk characterization involves assessing only the severity of the consequences. An example of a chronic risk scenario might be the toxicity to marine organisms due to low-level chemical releases from anti-biofouling paints and coatings that may be used on devices, and the effect that the level of toxicity may have on marine flora and fauna. Between these two extremes are intermittent events, such as encounters between fish and rotating tidal turbine blades that will occur only when fish are present and the tidal device is turning. A key feature of understanding risk is describing the uncertainty associated with the occurrence of an episodic, intermittent, or chronic event, as well as the uncertainty of the resulting consequences.

ocean energy↗