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At least 253 records · Page 14

Speculation and replication in temperature accelerated dynamics

Accelerated Molecular Dynamics (AMD) is a class of MD-based algorithms for the long-time scale simulation of atomistic systems that are characterized by rare-event transitions. Temperature-Accelerated Dynamics (TAD), a traditional AMD approach, hastens state-to-state transitions by performing MD at an elevated temperature. Recently, Speculatively-Parallel TAD (SpecTAD) was introduced, allowing the TAD procedure to exploit parallel computing systems by concurrently executing in a dynamically generated list of speculative future states. Although speculation can be very powerful, it is not always the most efficient use of parallel resources. In this paper, we compare the performance of speculative parallelism with a replica-based technique, similar to the Parallel Replica Dynamics method. A hybrid SpecTAD approach is also presented, in which each speculation process is further accelerated by a local set of replicas. Finally and overall, this work motivates the use of hybrid parallelism whenever possible, as some combination of speculation and replication is typically most efficient.

36 MATERIALS SCIENCE↗

Improve Replication of In-service Mechanical Environments

Structural dynamic testing is a common method for determining if the design of a component of a system will mechanically fail when deployed into its field environment. To satisfy the test's goal, the mechanical stresses must be replicated. Structural dynamic testing is commonly executed on a shaker table or a shock apparatus such as a drop table or a resonant plate. These apparatus impart a force or load on the component through a test fixture that connects the unit under test to the apparatus. Because the test fixture is directly connected to the unit under test, the fixture modifies the structural dynamics of the system, thus varying the locations and relative levels of stress on the unit under test. This may lead to a false positive or negative indication if the unit under test will fail in its field environment depending on the environment and the test fixture. This body of research utilizes topology optimization using the Plato software to design a test fixture that attaches to the unit under test that matches the dynamic impedance of the next level of assembly. The optimization's objective function is the difference between the field configuration and the laboratory configuration's frequency response functions. It was found that this objective function had many local minima and posed difficulties in converging to an acceptable solution. A case study is presented that uses this objective function and although the results are not perfect, they are quantifiably better than the current method of using a sufficiently stiff fixture.

42 ENGINEERING↗

FY18 ASC P&EM L2 Milestone 6356: Improve Replication of In-service Mechanical Environments. Executive Summary

The overall goal of this work was to improve the modeling of laboratory shock and vibration testing. Laboratory shock and vibration testing is used to qualify Nuclear Weapon components for the environment they will experience in the field. Standard practice is to use rigid test fixtures so that no spurious modes are introduced during laboratory testing. Rigid test fixtures may however in some cases change the dynamics of the component being tested, resulting in laboratory testing being more severe than what would occur in the field. This milestone investigated the use of topology optimization to create laboratory test fixtures that would better replicate the dynamics that components experience in field environments.

42 ENGINEERING↗

Replicated Computational Results (RCR) Report for "Adaptive Precision Block-Jacobi for High Performance Preconditioning in the Ginkgo Linear Algebra Software''

In, a practical implementation of a novel adaptive precision block-Jacobi preconditioner is introduced. In particular, the authors present a heavily-tuned GPU implementation of the adaptive precision block-Jacobi preconditioner within the Ginkgo numerical linear algebra library. The performance of the methodology and implementation is demonstrated using the proposed preconditioning scheme within Ginkgo’s high-performance Conjugate Gradient (CG) implementation on an NVIDIA Volta GPU. In this report, we replicate a subset of the computational results presented in. The focus is generating results from Fig. 9 to evaluate the performance of using Ginkgo’s CG solver integrated with either the full or the adaptive precision block-Jacobi preconditioner applied to a variety of test cases

97 MATHEMATICS AND COMPUTING↗

SCALE Calculations Replicating ARH-600 Data

This report documents Standardized Computer Analyses for Licensing Evaluation (SCALE) calculations replicating data from the ARH-600 criticality handbook. These calculations complement those reproduced with MCNP in PRC-NS-00009. Calculations were performed with SCALE version 6.1, using the v7-238 cross section library. The original ARH-600 data were calculated by the Atlantic Richfield Hanford (ARH) Company starting in the 1960s, and Monte Carlo N-Particle (MCNP) calculations were performed by the Hanford Plateau Remediation Company in 2010. This report is not intended to replace final analysis of fissile systems by qualified criticality personnel.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

A Single Amino Acid Substitution in the Matrix Protein (M51R) of Vesicular Stomatitis New Jersey Virus Impairs Replication in Cultured Porcine Macrophages and Results in Significant Attenuation in Pigs

In this study, we explore the virulence of vesicular stomatitis New Jersey virus (VSNJV) in pigs and its potential relationship with the virus’s ability to modulate innate responses. For this purpose, we developed a mutant of the highly virulent strain NJ0612NME6, containing a single amino acid substitution in the matrix protein (M51R). The M51R mutant of NJ0612NME6 was unable to suppress the transcription of genes associated with the innate immune response both in primary fetal porcine kidney cells and porcine primary macrophage cultures. Impaired viral growth was observed only in porcine macrophage cultures, indicating that the M51 residue is required for efficient replication of VSNJV in these cells. Furthermore, when inoculated in pigs by intradermal scarification of the snout, M51R infection was characterized by decreased clinical signs including reduced fever and development of less and smaller secondary vesicular lesions. Pigs infected with M51R had decreased levels of viral shedding and absence of RNAemia compared to the parental virus. The ability of the mutant virus to infect pigs by direct contact remained intact, indicating that the M51R mutation resulted in a partially attenuated phenotype capable of causing primary lesions and transmitting to sentinel pigs. Collectively, our results show a positive correlation between the ability of VSNJV to counteract the innate immune response in swine macrophage cultures and the level of virulence in pigs, a natural host of this virus. More studies are encouraged to evaluate the interaction of VSNJV with macrophages and other components of the immune response in pigs.

59 BASIC BIOLOGICAL SCIENCES↗

EcoFAB 3.0: a sterile system for studying sorghum that replicates previous field and greenhouse observations

Introduction Studying plant-microbe interactions is one of the key elements in understanding the path to sustainable agricultural practices. These interactions play a crucial role in ensuring survival of healthy plants, soil and microbial communities. Many platforms have been developed over the years to isolate these highly complex interactions however, these are designed for small model plants. This creates a need for complementary devices for larger plants, such as sorghum. Methods This work introduces a novel platform, EcoFAB 3.0, which is designed to enable studying bioenergy plants such as sorghum for up to 4 weeks in a controlled sterile environment. Several other advantages of this platform such as dark root chambers and user-friendly assembly are also discussed in this work. Results and discussion EcoFAB 3.0 was found to replicate previous greenhouse and field observations when comparing an engineered sorghum line overproducing 4-hydroxybenzoic acid (4-HBA) and wildtype (variety BTx430). Consistent with greenhouse and field observations, it was found that the engineered line of sorghum grown in EcoFAB 3.0 had a higher 4-HBA content and a lower dry biomass.

Gupta, Kshitiz↗

The Interaction between the DOCK7 Protein and the E2 Protein of Classical Swine Fever Virus Is Not Involved with Viral Replication or Pathogenicity

The classical swine fever virus (CSFV) particle consists of three glycoproteins, all of which have been shown to be important proteins involved in many virus functions, including interaction with several host proteins. One of these proteins, E2, has been shown to be directly involved with adsorption to the host cell and important for virus virulence. Using the yeast two-hybrid system, we have previously shown that CSFV E2 specifically interacts with the (DOCK7) dedicator of cytokinesis, a scaffolding protein. In this report, the interaction between E2 and DOCK7 was evaluated. To confirm the yeast two-hybrid results and to determine that DOCK7 interacts in swine cells with E2, we performed co-immunoprecipitation and proximity ligation assay (PLA). After demonstrating the protein interaction in swine cells, E2 amino acid residues Y65, V283, and T149 were determined to be critical for interaction with Dock7 by using a random mutated library of E2 and a reverse yeast two-hybrid approach. That disruption of these three residues with mutations Y65F, V283D, and T149A abrogated the Dock7-E2 protein interaction. These mutations were then introduced into a recombinant CSFV, E2DOCK7v, by a reverse genomics approach using the highly virulent CSFV Brescia isolate as a backbone. E2DOCKv was shown to have similar growth kinetics in swine primary macrophages and SK6 cell cultures to the parental Brescia strain. Similarly, E2DOCK7v demonstrated a similar level of virulence to the parental Brescia when inoculated in domestic pigs. Animals intranasally inoculated with 10 5 TCID 50 developed a lethal form of clinical disease with virological and hematological kinetics changes indistinguishable from that produced by the parental strain. Therefore, interaction between CSFV E2 and host DOCK7 is not critically involved in the process of virus replication and disease production.

60 APPLIED LIFE SCIENCES↗

Replication Package for "Union-Find and Usability: A Case Study and Analysis of Rust Formal Verifier

This replication package is a case study on automated deductive verification for Rust for practical programs. It is a companion artifact to a corresponding usability study on verification titled "Union-Find and Usability: A Case Study and Analysis of Rust Formal Verifiers". It seeks to answer the question "Can Rust developers today use Rust verifiers to verify their code?". To answer this question, the study contrasts the verification experience of two mature Rust verifiers, Creusot and Prusti, by using the tools to develop a verified implementation of union-find in Rust. The union-find implementation is based on real-world code as used in the popular egg E-graph library. The artifact consists of two different verified libraries, one using Creusot and one using Prusti. The libraries have similar Rust interfaces and high-level proofs but differ in their details: Creusot and Prusti have different annotation languages and support different proof styles. Each implementation can be verified with its respective tool and compiles as a traditional Rust development.

Sarracino, John↗

A Distributed OpenCL Framework using Redundant Computation and Data Replication

Applications written solely in OpenCL or CUDA cannot execute on a cluster as a whole. Most previous approaches that extend these programming models to clusters are based on a common idea: designating a centralized host node and coordinating the other nodes with the host for computation. However, the centralized host node is a serious performance bottleneck when the number of nodes is large. In this paper, we propose a scalable and distributed OpenCL framework called SnuCL-D for large-scale clusters. SnuCL-D's remote device virtualization provides an OpenCL application with an illusion that all compute devices in a cluster are confined in a single node. To reduce the amount of control-message and data communication between nodes, SnuCL-D replicates the OpenCL host program execution and data in each node. We also propose a new OpenCL host API function and a queueing optimization technique that significantly reduce the overhead incurred by the previous centralized approaches. To show the effectiveness of SnuCL-D, we evaluate SnuCL-D with a microbenchmark and eleven benchmark applications on a large-scale CPU cluster and a medium-scale GPU cluster.

Kim, Junghyun↗

TableCalculator: a Transparent Public Tool to Replicate US NRC LLW Classification Table Calculations - 19395

Classification of Low-Level Waste (LLW) as Class A, B, C, or Greater than Class C (GTCC) is based on tables provided in Section 61.55 of Title 10 of the Code of Federal Regulations (CFR). Those tables were developed from model projections of dose to an inadvertent intruder in agricultural and construction scenarios at different times after closure of a LLW land disposal site. The calculations were performed with two FORTRAN codes, which are documented in US NRC guidance documents published in the early 1980's. Although the equations and parameter values used in the codes are publicly available, no modern, user-friendly implementation of the codes is known to US NRC staff. Because Very Low-Level Waste (VLLW) and GTCC waste disposal are related to the low end and high end of the existing LLW waste classifications, respectively, recent interest in options for disposal of VLLW and GTCC waste have generated public interest in the original assumptions made during the development of the LLW classification tables. Certain stakeholder analyses have recommended alternatives to the existing LLW concentration limits by calculating a projected intruder dose under different conditions than were evaluated in the original development of 10 CFR Part 61 (e.g., using more modern dosimetry or assuming deeper disposal) and comparing the radionuclide concentrations that result in a projected annual dose of 5 milliSieverts (mSv) (500 millirem (mrem)) total effective dose equivalent (TEDE) to the concentrations in the waste classification tables. However, beginning with the 10 CFR Part 61 LLW classification limits and modifying only one or two assumptions to generate a proposed concentration limit could lead to misleading results without a thorough analysis of whether other assumptions made in the original development of the waste classification tables remain valid. In particular, the US NRC made adjustments to the 10 CFR 61.55 table values during the rulemaking process based on qualitative considerations. Those adjustments mean that many of the values in the final tables cannot simply be assumed to quantitatively represent a 5 mSv (500 mrem) projected inadvertent intruder dose without an assessment of whether the technical bases used to develop the adjustments are applicable to the new analysis. Furthermore, the waste classification limits were based on the limiting critical organ dose rather than a TEDE. Therefore, any calculation based on the assumption that the waste classification limits correspond to 5 mSv (500 mrem) TEDE could benefit from consideration of how differences in exposure pathways could affect the limiting critical organ dose differently from the TEDE. To facilitate a more comprehensive understanding of the calculations used to develop the waste classification tables, the US NRC staff has developed a user-friendly tool to replicate the original calculations. Results were verified against output from the FORTRAN codes and the classification table values. The tool, TableCalculator, is expected to be made publicly available and will allow the user to trace the original calculations and to observe the effects of changes in disposal assumptions and other parameter values. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Replication of N[superscript 2],3-Ethenoguanine by DNA Polymerases

The unstable DNA adduct N2,3-ethenoguanine, a product of both exposure to the carcinogen vinyl chloride and of oxidative stress, was built into an oligonucleotide, using an isostere strategy to stabilize the glycosidic bond. This modification was then used to examine the cause of mutations by DNA polymerases, in terms of both the biochemistry of the lesion and a structure of the lesion within a polymerase.

59 BASIC BIOLOGICAL SCIENCES↗

Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

The CMG helicase is composed of Cdc45, Mcm2–7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7–4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2–7, braced by Cdc45–GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2–7 double hexamer. In addition, the Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.

59 BASIC BIOLOGICAL SCIENCES↗

Immunological Correlates of the HIV-1 Replication-Competent Reservoir Size

Understanding what shapes the latent human immunodeficiency virus type 1 (HIV-1) reservoir is critical for developing strategies for cure. Here, we measured frequency of persistent HIV-1 infection after 5 years of suppressive antiretroviral therapy initiated during chronic infection. Pretreatment CD8 + T-cell activation, nadir CD4 count, and CD4:CD8 ratio predicted reservoir size.

60 APPLIED LIFE SCIENCES↗