Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “replication”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening

Tyrosyl DNA-phosphodiesterase I (TDP1) repairs type IB topoisomerase (TOP1) cleavage complexes generated by TOP1 inhibitors commonly used as anticancer agents. TDP1 also removes DNA 3' end blocking lesions generated by chain-terminating nucleosides and alkylating agents, and base oxidation both in the nuclear and mitochondrial genomes. Combination therapy with TDP1 inhibitors is proposed to synergize with topoisomerase targeting drugs to enhance selectivity against cancer cells exhibiting deficiencies in parallel DNA repair pathways. A crystallographic fragment screening campaign against the catalytic domain of TDP1 was conducted to identify new lead compounds. Crystal structures revealed two fragments that bind to the TDP1 active site and exhibit inhibitory activity against TDP1. These fragments occupy a similar position in the TDP1 active site as seen in prior crystal structures of TDP1 with bound vanadate, a transition state mimic. Using structural insights into fragment binding, several fragment derivatives have been prepared and evaluated in biochemical assays. These results demonstrate that fragment-based methods can be a highly feasible approach toward the discovery of small-molecule chemical scaffolds to target TDP1, and for the first time, we provide co-crystal structures of small molecule inhibitors bound to TDP1, which could serve for the rational development of medicinal TDP1 inhibitors.

Lountos, George T.↗
DOE OSTI2022

Antiretroviral therapy for HIV and intrahepatic hepatitis C virus replication

HIV alters host responses to hepatitis C virus (HCV). However, the impact of antiretroviral therapy (ART) on HCV is rarely understood in relevant tissues and never before within individual hepatocytes. HIV and HCV kinetics were studied before and after ART initiation among 19 HIV/HCV co-infected persons. From five persons with the largest decline in plasma HCV RNA, liver tissues collected before and during ART, when plasma HIV RNA was undetectable, were studied. Here we used single-cell laser capture microdissection and quantitative PCR to assess intrahepatic HCV. Immunohistochemistry was performed to characterize intrahepatic immune cell populations. Plasma HCV RNA declined by 0.81 (0.52–1.60) log 10 IU/ml from a median (range) 7.26 (6.05–7.29) log 10 IU/ml and correlated with proportions of HCV-infected hepatocytes (r = 0.89, P = 2 × 10 -5 ), which declined from median (range) of 37% (6–49%) to 23% (0.5–52%) after plasma HIV clearance. Median (range) HCV RNA abundance within cells was unchanged in four of five participants. Liver T-cell abundance unexpectedly decreased, whereas natural killer (NK) and NK T-cell infiltration increased, correlating with changes in proportions of HCV-infected hepatocytes (r = -0.82 and r = -0.73, respectively). Hepatocyte expression of HLA-E, an NK cell restriction marker, correlated with proportions of HCV-infected hepatocytes (r = 0.79). These are the first data to show that ART control of HIV reduces the intrahepatic burden of HCV. Furthermore, our data suggest that HIV affects the pathogenesis of HCV infection by an NK/NK T-cell-mediated mechanism that may involve HLA-E and can be rescued, at least in part, by ART.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Practical State Machine Replication with Confidentiality

We study how to enable arbitrary randomized algorithms in Byzantine fault-tolerant (BFT) settings. We formalize a randomized BFT protocol and provide a simple and efficient construction that can be built on any existing BFT protocols while adding practically no overhead. We go one step further to revisit a confidential BFT protocol (Yin et al., SOSP '03). We show that their scheme is potentially susceptible to safety and confidentiality attacks. We then present a new protocol that is secure in the stronger model we formalize, by extending the idea of a randomized BFT protocol. Our protocol uses only efficient symmetric cryptography, while Yin et al.'s uses costly threshold signatures. We implemented and evaluated our protocols on microbenchmarks and real-world use cases. We show that our randomized BFT protocol is as efficient as conventional BFT protocols, and our confidential BFT protocol is two to three orders of magnitude faster than Yin et al.'s, which is less secure than ours.

Duan, Sisi↗
DOE OSTI2018

A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid

Polyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative-strand RNA virus. For this work, Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encapsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex. One polyamide molecule, UMSL1011, was found to inhibit infection of VSV. To confirm that the polyamide targeted the nucleocapsid, a nucleocapsid-like particle (NLP) was incubated with UMSL1011. The encapsidated RNA in the polyamide-treated NLP was protected from thermo-release and digestion by RNase A. UMSL1011 also inhibits viral RNA synthesis in the intracellular activity assay for the viral RNA-dependent RNA polymerase. The crystal structure revealed that UMSL1011 binds the structured RNA in the nucleocapsid. The conclusion of our studies is that the RNA in the nucleocapsid is a viable antiviral target of polyamides. Since the RNA structure in the nucleocapsid is similar in all negative-strand RNA viruses, polyamides may be optimized to target the specific RNA genome of a negative-strand RNA virus, such as respiratory syncytial virus and Ebola virus.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Parser for Sabin-to-Mahoney Transition Model of Quasispecies Replication

This code is a data parse for preparing output from the Qspp agent-based stochastic simulation model for plotting in Excel. This code is specific to a set of simulations that were run for the purpose of preparing data for a publication. It is necessary to make this code open-source in order to publish the model code (Qspp), which has already been released. There is a necessity of assuring that results from using Qspp for a publication

Ecale Zhou, Carol↗
DOE OSTI2020

X-ray verification of sol-gel resist shrinkage in substrate-conformal imprint lithography for a replicated blazed reflection grating

Surface-relief gratings fabricated through nanoimprint lithography (NIL) are prone to topographic distortion induced by resist shrinkage. Characterizing the impact of this effect on blazed diffraction efficiency is particularly important for applications in astrophysical spectroscopy at soft x-ray wavelengths ( λ ≈ 0.5 − 5 nm) that call for the mass-production of large-area grating replicas with sub-micron, sawtooth surface-relief profiles. A variant of NIL that lends itself well for this task is substrate-conformal imprint lithography (SCIL), which uses a flexible, composite stamp formed from a rigid master template to imprint nanoscale features in an inorganic resist that cures thermodynamically through a silica sol-gel process. While SCIL enables the production of several hundred imprints before stamp degradation and avoids many of the detriments associated with large-area imprinting in NIL, the sol-gel resist suffers shrinkage dependent on the post-imprint cure temperature. Through atomic force microscopy and diffraction-efficiency testing at beamline 6.3.2 of the Advanced Light Source, the impact of this effect on blaze response is constrained for a ∼160-nm-period grating replica cured at 90 ° C. Results demonstrate a ∼2 ° reduction in blaze angle relative to the master grating, which was fabricated by anisotropic wet etching in 〈311〉-oriented silicon to yield a facet angle close to 30 ° .

McCoy, Jake A. (ORCID:0000000216057517)↗
DOE OSTI2016

Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers

Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the “shock and kill” strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~10 6 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35–50 days, followed by in vivo experimental depletion of CD8 + cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~10 4 copies/ml) peaking at 5–12 days post-treatment. CD8 + cell depletion resulted in a more robust viral rebound (10 7 copies/ml) that was controlled upon CD8 + T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of the patterns of virus rebound after RMD administration and CD8 + cell depletion suggested that RMD impact on T cells is only transient and does not irreversibly alter the ability of SIV-specific T cells to control the reactivated virus.

Microbiology↗
DOE OSTI2014

A non-linear elastic constitutive framework for replicating plastic deformation in solids.

Ductile metals and other materials typically deform plastically under large applied loads; a behavior most often modeled using plastic deformation constitutive models. However, it is possible to capture some of the key behaviors of plastic deformation using only the framework for nonlinear elastic mechanics. In this paper, we develop a phenomenological, hysteretic, nonlinear elastic constitutive model that captures many of the features expected of a plastic deformation model. This model is based on calculating a secant modulus directly from a material s stress-strain curve. Scalar stress and strain values are obtained in three dimensions by using the von Mises invariants. Hysteresis is incorporated by tracking an additional history variable and assuming an elastic unloading response. This model is demonstrated in both single- and multi-element simulations under varying strain conditions.

Roberts, Scott Alan↗
DOE OSTI2016

Advancing Replicable Solutions for High-Performance Homes in the Southeast

The work presented in this report advances the goals of the U.S. Department of Energy Building America program by improving the energy performance of affordable and market-rate housing. Southface Energy Institute (Southface), part of the U.S. Department of Energy Building America research team Partnership for Home Innovation, worked with owners and builders with various market constraints and ultimate goals for three projects in three climate zones (CZs): Savannah Gardens in Savannah, Georgia (CZ 2); JMC Patrick Square in Clemson, South Carolina (CZ 3); and LaFayette in LaFayette, Georgia (CZ 4). This report documents the design process, computational energy modeling, construction, envelope performance metrics, long-term monitoring results, and successes and failures of the design and execution of these high-performance homes.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2016

Advancing Replicable Solutions for High-Performance Homes in the Southeast

Southface Energy Institute (Southface) partnered with owners and/or builders with various market constraints and ultimate goals for three projects in different climate zones: Savannah, GA (CZ 2), Clemson, SC (CZ 3), and LaFayette, GA (CZ 4). This report documents the design process, computational energy modeling, construction, envelope performance metrics, long-term monitoring results, and successes and failures of the design and execution of these high performance homes. The three bedroom/two bathroom test home in Savannah Gardens on an elevated slab foundation has a semi-conditioned, encapsulated attic. A neighboring home built to EarthCraft specifications was also monitored as a control for exterior foam insulation and a heat pump water heater (HPWH). For the JMC Patrick Square, a single-story project in Clemson, the small-scale production builder wanted to increase their level of energy efficiency beyond their current green building practices, including bringing ducts into conditioned space. Through a combination of upgrade measures the team met this goal and achieved many Zero Energy Ready Home requirements. LaFayette Housing Authority undertook a development of 30 affordable rental housing units in 15 duplexes in LaFayette, GA. Because they would be long-term owners, their priorities were low utility bills for the residents and durable, maintainable buildings. The team employed BEopt to optimize buildling envelope and systems choices, including 2x6 advanced framed walls, insulated slab, and heat pump water heater in a utility closet which was ducted to/from an encapsulated attic.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2018

Calibration of laboratory aging practice to replicate changes to roof albedo in a Chinese city

Highly reflective roofs can save building air conditioning energy, mitigate the urban heat island, and offset CO 2 emissions. A laboratory aging methodology was developed to simulate change in the solar reflectances of field-applied roof coatings induced by one year of natural exposure in Guangzhou (China). The approach compared the changes in solar reflectance spectra observed in the naturally exposed materials with those obtained following a three-stage laboratory procedure: conditioning, soiling, and weathering. The method was systematically modified over five trials by adjusting the key variables in laboratory aging: composition of the soiling mixture, deposition mass, and conditions of soiling application. Tests were performed using a small number of specimens. Simulating exposure in Guangzhou required a loading of soiling agents greater than that used to simulate US cites. In the final trial, the reduction in solar reflectance was reproduced to within an average of 0.02 for three of the six products, and to within an average of 0.06 for the remaining three products.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗