Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “BASIC INTERACTIONS”

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 1,459 records · Page 81
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

iPNHOT: a knowledge-based approach for identifying protein-nucleic acid interaction hot spots

The interaction between proteins and nucleic acids plays pivotal roles in various biological processes such as transcription, translation, and gene regulation. Hot spots are a small set of residues that contribute most to the binding affinity of a protein-nucleic acid interaction. Compared to the extensive studies of the hot spots on protein-protein interfaces, the hot spot residues within protein-nucleic acids interfaces remain less well-studied, in part because mutagenesis data for protein-nucleic acids interaction are not as abundant as that for protein-protein interactions. In this study, we built a new computational model, iPNHOT, to effectively predict hot spot residues on protein-nucleic acids interfaces. One training data set and an independent test set were collected from dbAMEPNI and some recent literature, respectively. To build our model, we generated 97 different sequential and structural features and used a two-step strategy to select the relevant features. The final model was built based only on 7 features using a support vector machine (SVM). The features include two unique features such as ΔSASsa 1/2 and esp3, which are newly proposed in this study. Based on the cross validation results, our model gave F1 score and AUROC as 0.725 and 0.807 on the subset collected from ProNIT, respectively, compared to 0.407 and 0.670 of mCSM-NA, a state-of-the art model to predict the thermodynamic effects of protein-nucleic acid interaction. The iPNHOT model was further tested on the independent test set, which showed that our model outperformed other methods. Here, by collecting data from a recently published database dbAMEPNI, we proposed a new model, iPNHOT, to predict hotspots on both protein-DNA and protein-RNA interfaces. The results show that our model outperforms the existing state-of-art models. Our model is available for users through a webserver: http://zhulab.ahu.edu.cn/iPNHOT/.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

TU-AB-207A-03: Image Quality, Dose, and Clinical Applications

Practicing medical physicists are often time charged with the tasks of evaluating and troubleshooting complex image quality issues related to CT scanners. This course will equip them with a solid and practical understanding of common CT imaging chain and its major components with emphasis on acquisition physics and hardware, reconstruction, artifacts, image quality, dose, and advanced clinical applications. The core objective is to explain the effects of these major system components on the image quality. This course will not focus on the rapid-changing advanced technologies given the two-hour time limit, but the fundamental principles discussed in this course may facilitate better understanding of those more complicated technologies. The course will begin with an overview of CT acquisition physics and geometry. X-ray tube and CT detector are important acquisition hardware critical to the overall image quality. Each of these two subsystems consists of several major components. An in-depth description of the function and failure modes of these components will be provided. Examples of artifacts related to these failure modes will be presented: off-focal radiation, tube arcing, heel effect, oil bubble, offset drift effect, cross-talk effect, and bad pixels. The fundamentals of CT image reconstruction will first be discussed on an intuitive level. Approaches that do not require rigorous derivation of mathematical formulations will be presented. This is followed by a detailed derivation of the Fourier slice theorem: the foundation of the FBP algorithm. FBP for parallel-beam, fan-beam, and cone-beam geometries will be discussed. To address the issue of radiation dose related to x-ray CT, recent advances in iterative reconstruction, their advantages, and clinical applications will also be described. Because of the nature of fundamental physics and mathematics, limitations in data acquisition, and non-ideal conditions of major system components, image artifact often arise in the reconstructed images. Because of the limited scope of this course, only major imaging artifacts, their appearance, and possible mitigation and corrections will be discussed. Assessment of the performance of a CT scanner is a complicated subject. Procedures to measure common image quality metrics such as high contrast spatial resolution, low contrast detectability, and slice profile will be described. The reason why these metrics used for FBP may not be sufficient for statistical iterative reconstruction will be explained. Optimizing radiation dose requires comprehension of CT dose metrics. This course will briefly describe various dose metrics, and interaction with acquisition parameters and patient habitus. CT is among the most frequently used imaging tools due to its superior image quality, easy to operate, and a broad range of applications. This course will present several interesting CT applications such as a mobile CT unit on an ambulance for stroke patients, low dose lung cancer screening, and single heartbeat cardiac CT. Learning Objectives: Understand the function and impact of major components of X-ray tube on the image quality. Understand the function and impact of major components of CT detector on the image quality. Be familiar with the basic procedure of CT image reconstruction. Understand the effect of image reconstruction on CT image quality and artifacts. Understand the root causes of common CT image artifacts. Be familiar with image quality metrics especially high and low contrast resolution, noise power spectrum, slice sensitivity profile, etc. Understand why basic image quality metrics used for FBP may not be sufficient to characterize the performance of advanced iterative reconstruction. Be familiar with various CT dose metrics and their interaction with acquisition parameters. New development in advanced CT clinical applications. JH: Employee of GE Healthcare. FD: No disclosure.; J. Hsieh, Jiang Hsieh is an employee of GE Healthcare.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Giant virus diversity and host interactions through global metagenomics

Our current knowledge about nucleocytoplasmic large DNA viruses (NCLDVs) is largely derived from viral isolates that are co-cultivated with protists and algae. Here we reconstructed 2,074 NCLDV genomes from sampling sites across the globe by building on the rapidly increasing amount of publicly available metagenome data. This led to an 11-fold increase in phylogenetic diversity and a parallel 10-fold expansion in functional diversity. Analysis of 58,023 major capsid proteins from large and giant viruses using metagenomic data revealed the global distribution patterns and cosmopolitan nature of these viruses. The discovered viral genomes encoded a wide range of proteins with putative roles in photosynthesis and diverse substrate transport processes, indicating that host reprogramming is probably a common strategy in the NCLDVs. Furthermore, inferences of horizontal gene transfer connected viral lineages to diverse eukaryotic hosts. We anticipate that the global diversity of NCLDVs that we describe here will establish giant viruses-which are associated with most major eukaryotic lineages-as important players in ecosystems across Earth's biomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

An efficient three-dimensional rhizosphere modeling capability to study the effect of root system architecture on soil water and reactive transport

This research was to develop a rhizosphere modeling capability for plant-soil interactions by integrating water and ion uptake and release from three dimensional (3D) root systems and 3D variably saturated flow and multicomponent reactive transport in soil. We combined open source software for simulating plant and soil interactions with parallel processing computational technologies to address highly-resolved root system architecture and soil hydrobiogeochemical processes. Simulation capability was demonstrated on Brachypodium distachyon . Our demonstration problem showed that availability of water and plant nutrients is controlled by the interplay between 1) transpiration-driven cycles of water uptake, root zone saturation and desaturation; 2) sorption and desorption via competitive ion exchange; 3) buildup of ions not taken up during kinetic uptake of nutrients/ions from pore water; and 4) advection, dispersion, and diffusion of ions in the soil. The uptake of water and ions by individual roots leads to dynamic, local gradients in ion concentrations. The resulting higher solution ionic strength can lead to increasing sorption of K+ and NH4+ on the soil exchange sites, despite their preferential absorption by roots. The modeling framework makes it possible to explore alternative conceptual models and improve the understanding of the biogeochemical and physical environment within the rhizosphere.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

A Mo-anode-based in-house source for small-angle X-ray scattering measurements of biological macromolecules

We demonstrate the use of a molybdenum-anode-based in-house small-angle X-ray scattering (SAXS) setup to study biological macromolecules in solution. Our system consists of a microfocus X-ray tube delivering a highly collimated flux of 2.5 × 10{sup 6} photons/s at a beam size of 1.2 × 1.2 mm{sup 2} at the collimation path exit and a maximum beam divergence of 0.16 mrad. The resulting observable scattering vectors q are in the range of 0.38 Å{sup −1} down to 0.009 Å{sup −1} in SAXS configuration and of 0.26 Å{sup −1} up to 5.7 Å{sup −1} in wide-angle X-ray scattering (WAXS) mode. To determine the capabilities of the instrument, we collected SAXS data on weakly scattering biological macromolecules including proteins and a nucleic acid sample with molecular weights varying from ∼12 to 69 kDa and concentrations of 1.5–24 mg/ml. The measured scattering data display a high signal-to-noise ratio up to q-values of ∼0.2 Å{sup −1} allowing for an accurate structural characterization of the samples. Moreover, the in-house source data are of sufficient quality to perform ab initio 3D structure reconstructions that are in excellent agreement with the available crystallographic structures. In addition, measurements for the detergent decyl-maltoside show that the setup can be used to determine the size, shape, and interactions (as characterized by the second virial coefficient) of detergent micelles. This demonstrates that the use of a Mo-anode based in-house source is sufficient to determine basic geometric parameters and 3D shapes of biomolecules and presents a viable alternative to valuable beam time at third generation synchrotron sources.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2021

Manganese uptake by red maples in response to mineral dissolution rates in soil

Manganese (Mn) is an essential plant micronutrient that influences photosynthesis, ecosystem productivity, and soil carbon storage. Our objective was to quantify how Mn uptake by forest vegetation relates to Mn release into soil solution through mineral dissolution. In this work, a greenhouse pot experiment was conducted to quantify Mn uptake by red maple saplings as a function of mineral solubility to test whether Mn uptake was limited by the supply of Mn to soil solution. Differences in soil microbial community composition between treatments, particularly amongst Mn cycling bacteria and fungi, were also evaluated to assess potential microbial impacts on observed Mn fluxes. Plant Mn uptake was highest in systems supplied with dissolved Mn(II) because it was not kinetically limited by mineral weathering. Mn uptake was also higher in systems supplied with a fast-weathering substrate (shale containing Mn(II)-bearing pyrite) than a slow-weathering substrate (Mn(IV)-oxide). However, vegetation accumulated a decreasing proportion of available Mn with increasing solubility, indicating that uptake was tempered relative to solubility. The presence of bacterial phyla containing known Mn-oxidizing bacteria indicates the potential for Mn-oxidizing bacteria to influence Mn solubility within Mn-oxide and dissolved Mn treatments. A relatively low abundance of these bacteria points to their limited capacity to oxidize and retain Mn in the shale treatments, consistent with substantial Mn leaching. We conclude that Mn uptake was primarily controlled by dissolution rates of Mn-bearing minerals but modified by biological processes. The quantitative framework presented here can guide understanding of how biogeochemical processes control element cycling between plants and soils.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal

Highlights: Black-Right-Pointing-Pointer Full-length 21.5-kDa MBP isoform is translocated to the nucleus. Black-Right-Pointing-Pointer We hypothesized that the exon-II-encoded sequence contained the NLS. Black-Right-Pointing-Pointer We mutated this sequence in RFP-tagged constructs and transfected N19-cells. Black-Right-Pointing-Pointer Abolition of two key positively-charged residues resulted in loss of nuclear-trafficking. Black-Right-Pointing-Pointer The 21.5-kDa isoform of classic MBP contains a non-traditional PY-NLS. -- Abstract: The predominant 18.5-kDa classic myelin basic protein (MBP) is mainly responsible for compaction of the myelin sheath in the central nervous system, but is multifunctional, having numerous interactions with Ca{sup 2+}-calmodulin, actin, tubulin, and SH3-domains, and can tether these proteins to a lipid membrane in vitro. The full-length 21.5-kDa MBP isoform has an additional 26 residues encoded by exon-II of the classic gene, which causes it to be trafficked to the nucleus of oligodendrocytes (OLGs). We have performed site-directed mutagenesis of selected residues within this segment in red fluorescent protein (RFP)-tagged constructs, which were then transfected into the immortalized N19-OLG cell line to view protein localization using epifluorescence microscopy. We found that 21.5-kDa MBP contains two non-traditional PY-nuclear-localization signals, and that arginine and lysine residues within these motifs were involved in subcellular trafficking of this protein to the nucleus, where it may have functional roles during myelinogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Rational design of antimicrobial peptides targeting Gram-negative bacteria

Membrane-targeting host antimicrobial peptides (AMPs) can kill or inhibit the growth of Gram-negative bacteria. However, the evolution of resistance among microbes poses a substantial barrier to the long-term utility of the host AMPs. Combining experiment and molecular dynamics simulations, we demonstrate that terminal carboxyl capping enhances both membrane insertion and antibacterial activity of an AMP called P1. Furthermore, we show that a bacterial strain with evolved resistance to this peptide becomes susceptible to P1 variants with either backbone capping or lysine-to-arginine substitutions. Our results suggest that cocktails of closely related AMPs may be useful in overcoming evolved resistance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Design of compact ultrafast microscopes for single- and multi-shot imaging with MeV electrons

Ultrafast high-energy electron microscopy, taking advantage of strong interaction of electrons with matter while minimizing space charge problems, can be used to address a wide range of grand challenges in basics energy sciences. However, MeV-electron lenses are inherently bulky and expensive, preventing them from acceptance in a broad scientific community. In this article, we report our novel design of a compact, low-cost imaging-lens system for MeV-electrons based on quadrupole multiplets, including triplet, quadruplet and quintuplet, both symmetric and asymmetric. We compare optical performance of quadrupole-based condenser, objective and projector lenses with that of the traditional round-lenses and discuss the strategy for their practical use in constructing MeV-electron microscopes for high spatial and temporal resolution single- and multi-shot imaging. Combining the compound electron-optical system with a photocathode radiofrequency (RF) gun, such a MeV electron microscope can be fit into a smallsized laboratory for ultrafast observations and measurements.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2012

In vivo subcellular localization of Mal de Rio Cuarto virus (MRCV) non-structural proteins in insect cells reveals their putative functions

The in vivo subcellular localization of Mal de Rio Cuarto virus (MRCV, Fijivirus, Reoviridae) non-structural proteins fused to GFP was analyzed by confocal microscopy. P5-1 showed a cytoplasmic vesicular-like distribution that was lost upon deleting its PDZ binding TKF motif, suggesting that P5-1 interacts with cellular PDZ proteins. P5-2 located at the nucleus and its nuclear import was affected by the deletion of its basic C-termini. P7-1 and P7-2 also entered the nucleus and therefore, along with P5-2, could function as regulators of host gene expression. P6 located in the cytoplasm and in perinuclear cloud-like inclusions, was driven to P9-1 viroplasm-like structures and co-localized with P7-2, P10 and {alpha}-tubulin, suggesting its involvement in viroplasm formation and viral intracellular movement. Finally, P9-2 was N-glycosylated and located at the plasma membrane in association with filopodia-like protrusions containing actin, suggesting a possible role in virus cell-to-cell movement and spread.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Substrate Promotes Productive Gas Binding in the α-Ketoglutarate-Dependent Oxygenase FIH

The Fe 2+ /α-ketoglutarate (αKG)-dependent oxygenases use molecular oxygen to conduct a wide variety of reactions with important biological implications, such as DNA base excision repair, histone demethylation, and the cellular hypoxia response. These enzymes follow a sequential mechanism in which O 2 binds and reacts after the primary substrate binds, making those structural factors that promote productive O 2 binding central to their chemistry. A large challenge in this field is to identify strategies that engender productive turnover. Factor inhibiting HIF (FIH) is a Fe 2+ /αKG-dependent oxygenase that forms part of the O 2 sensing machinery in human cells by hydroxylating the C-terminal transactivation domain (CTAD) found within the HIF-1α protein. In this work, the structure of FIH was determined with the O 2 analogue NO bound to Fe, offering the first direct insight into the gas binding geometry in this enzyme. Through a combination of density functional theory calculations, {FeNO} 7 electron paramagnetic resonance spectroscopy, and ultraviolet–visible absorption spectroscopy, we demonstrate that CTAD binding stimulates O 2 reactivity by altering the orientation of the bound gas molecule. Although unliganded FIH binds NO with moderate affinity, the bound gas can adopt either of two orientations with similar stability; upon CTAD binding, NO adopts a single preferred orientation that is appropriate for supporting oxidative decarboxylation. Combined with other studies of related enzymes, our data suggest that substrate-induced reorientation of bound O 2 is the mechanism utilized by the αKG oxygenases to tightly couple O 2 activation to substrate hydroxylation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Structural and Biophysical Characterization of the Mycobacterium tuberculosis Protein Rv0577, a Protein Associated with Neutral Red Staining of Virulent Tuberculosis Strains and Homologue of the Streptomyces coelicolor Protein KbpA

The 261-residue Mycobacterium tuberculosis protein Rv0577 is a prominent antigen in tuberculosis patients, the responsible component for neutral red staining of virulent strains of M. tuberculosis, a putative component in a methylglyoxal detoxification pathway, and an agonist of toll-like receptor 2. It also has 36% sequence identity to AfsK-binding protein A (KbpA), a component in the complex secondary metabolite pathways in the Streptomycetes genus from which many commercial antibiotics are derived. To gain insight into the biological function of Rv0577 and the family of KpbA kinase regulators, the crystal structure for Rv0577 was determined to a resolution of 1.75 Å (3OXH), binding properties with neutral red and deoxyadenosine (Ado) surveyed, backbone dynamics measured, and thermal stability assayed by CD spectroscopy. The protein is composed of four approximate repeats with an topology arranged radially in consecutive pairs to form two continuous eight-strand -sheets capped on both ends with an -helix. The two -sheets intersect in the center at roughly a right angle and form an asymmetric deep “saddle” on both sides of the protein, saddle one (P11 to A129) and saddle two (L143 to A258), that may serve to bind ligands. NMR chemical shift perturbation experiments show that neutral red binds to Rv0577, further cementing the role of Rv0577 in the neutral red staining of virulent strains of M. tuberculosis. Similar experiments show that adenosine also bind to Rv0577, although less tightly, with estimated dissociation constants of 4.1 ± 0.3 mM for saddle one and > 1 M for saddle two. Heteronuclear steady-state {1H}-15N NOE, T1, and T2 values were generally uniform through-out the sequence with only a few modest pockets of differences suggestive of slightly different motion in loops between -strands in saddle 1. Circular dichroism spectroscopy characterization of the thermal stability of Rv0577 indicated irreversible unfolding upon heating with an estimated melting temperature of 56 °C. While it is not known if Rv0577 has a kinase regulatory role similar to its Streptomyces homolog KbpA, protein kinase and phosphatase signaling help M. tuberculosis adapt to the hostile host environment during infections. Consequently, new anti-tuberculosis drugs targeting Rv0577 may act by interfering with multiple mechanisms; a potential signaling machinery as well as toll-like receptor 2 activation and the methylglyoxal detoxification pathway.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Structural Insight into a Novel Formyltransferase and Evolution to a Nonribosomal Peptide Synthetase Tailoring Domain

Nonribosomal peptide synthetases (NRPSs) increase the chemical diversity of their products by acquiring tailoring domains. Linear gramicidin synthetase starts with a tailoring formylation (F) domain, which likely originated from a sugar formyltransferase (FT) gene. Here, we present studies on an Anoxybacillus kamchatkensis sugar FT representative of the prehorizontal gene transfer FT. Gene cluster analysis reveals that this FT acts on a UDP-sugar in a novel pathway for synthesis of a 7-formamido derivative of CMP-pseudaminic acid. We recapitulate the pathway up to and including the formylation step in vitro, experimentally demonstrating the role of the FT. We also present X-ray crystal structures of the FT alone and with ligands, which unveil contrasts with other structurally characterized sugar FTs and show close structural similarity with the F domain. In conclusion, the structures reveal insights into the adaptations that were needed to co-opt and evolve a sugar FT into a functional and useful NRPS domain.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗