Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “conformance”

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 649 records · Page 36
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

HIV-1 GP140 immunogens comprising modified NHR1 regions that stabilize pre-fusion envelope conformations

The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.

Kong, Leopold↗
DOE OSTI2022

On-Demand Designing of Cathode Internal Surface Architecture for Dramatic Enhancement of SOFC Performance and Durability

This project is aimed to design and modify the internal surfaces of porous composite cathode from currently commercially viable Solid Oxide Fuel Cells (SOFCs), using additive manufacturing process of Atomic Layer Deposition (ALD). The material systems being investigated are commercial composite electrodes complex three-dimensional topographies. In term of the chemistry of the ALD layer applied on the internal surface of the porous cathode, this project has employed commercially relevant electrolyte, electrocatalyst and noble metal materials set. Such materials are fully compatible with the commercial fuel cells, and this project has developed special nanostructure on the surface of the commercial composite cathodes. The formation of the designed nanoarchitecture on the surface of SOFC cathode has been achieved through precise control of ALD parameters and their effect on overall cell performance and resultant electrochemical reaction mechanism of cathodes has been investigated through full cell electrochemical performance testing and nanostructure characterization by transmission electron microscopy (TEM). Under the support of this award, following has been achieved: (1). For cathode materials in solid oxide fuel cells (SOFCs), such as perovskite mixed conductor La 0.6 Sr 0.4 Co 0.2 Fe 0.8 O 3-x (LSCF), cation surface segregation and consequently losing conductivity and active sites for the oxygen reduction reaction (ORR) are problematic. To mitigate the cation segregation and enhance SOFC durability, further decorating the internal backbone surface using the desired electrocatalysts could be a promoting approach. Commonly, the cation segregation such as Sr is very volatile, so the effective surface decoration is ideally conformal. Nevertheless, the conformal surface coating would inevitably alter the ORR pathways that initially take place on the surface of the backbone. To reveal the impact of the conformal coating on both the catalytic activity and the conductivity of the cathode, the unary electrocatalyst of Pt or CoO x , was applied to the LSCF/SDC composite electrode of inherently functional SOFCs, respectively. Both ALD coating layers evolve strong interaction with the LSCF composite cathode. Upon operations, the Pt coating layer remains conformal on LSCF grain surfaces but turns into discrete particles on SDC grain surfaces. Meanwhile, CoO x conformal coating grows to be the discrete nanograins on both the LSCF and SDC grains. ALD coating of the cathode alone reduces the ohmic resistance up to 28 % for the entire cells. The increased conductivity induced by the ALD coating of Pt or CoO x is ascribed to different mechanisms. For the inherent functional SOFCs, the present study presents a novel and feasible approach to apply a conformal, dense coating layer on the surface of a mixed conductor, simultaneously increasing the conductivity and durability of the SOFC cathode. (2). High resistance of the oxygen electrode still significantly hinders the state-of-the-art Solid Oxide Fuel Cells (SOFCs). In particular, for an oxygen electrode consisting of mixed electronic and ionic conductors, such as perovskite lanthanum strontium cobalt ferrite (LSCF), it deteriorates due to its low chemical stability of the grain surface. Such degradation is often associated with the segregation of cations. To prevent the cation surface segregation and its resultant perovskite phase decomposition, we demonstrate a conformal ultra-thin (7-10 nm) surface heterogeneous coating layer consisting of subjacent discrete Pt nanoparticles capped with a superjacent fully dense conformal CoO x layer. The performance studies indicate the ALD coating reduces the cell series resistance by up to 40 %. The conformal CoO x layer consists of randomly orientated but single-layered nanograins, with high-density intergranular and surface grain boundaries serving as the electrochemical reaction sites and facilitating mass transport. The conformal coating layer appears to have successfully suppressed the Sr outward diffusion and confined the Sr enriched layer to a ~ 2 nm interface perovskite phase between the coating layer and the LSCF grain surface. Moreover, this ultra-thin Sr enriched perovskite layer presumably possesses high oxygen vacancy and high ionic conductivity and further imposes tensile strain to the LSCF grain surfaces. With the combination of a conformal CoO x nanoionics, Sr enriched layer, and its strained interface, the ALD coating induced surface layer is estimated to have a conductivity of ~ 1.27x10 4 S/cm, which is over two orders magnitude of that from LSCF at 750 ºC.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2020

Massive celestial fermions

In an effort to further the study of amplitudes in the celestial CFT (CCFT), we construct conformal primary wavefunctions for massive fermions. Upon explicitly calculating the wavefunctions for Dirac fermions, we deduce the corresponding transformation of momentum space amplitudes to celestial amplitudes. The shadow wavefunctions are shown to have opposite spin and conformal dimension 2 - Δ. The Dirac conformal primary wave- functions are delta function normalizable with respect to the Dirac inner product provided they lie on the principal series with conformal dimension Δ = 1 + iλ for λ ∈ $\mathbb{R}$. It is shown that there are two choices of a complete basis: single spin J=$\frac{1}{2}$ or J=-$\frac{1}{2}$ and λ ∈ $\mathbb{R}$ or multiple spin J=±$\frac{1}{2}$ and λ $\mathbb{R}$ +∪0 . The massless limit of the Dirac conformal primary wavefunctions is shown to agree with previous literature. The momentum generators on the celestial sphere are derived and, along with the Lorentz generators, form a representation of the Poincaré algebra. Finally, we show that the massive spin-1 conformal primary wavefunctions can be constructed from the Dirac conformal primary wavefunctions using the standard Clebsch-Gordan coefficients. We use this procedure to write the massive spin-$\frac{3}{2}$, Rarita-Schwinger, conformal primary wavefunctions. This provides a prescription for constructing all massive fermionic and bosonic conformal primary wavefunctions starting from spin-$\frac{1}{2}$.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2023

Reduced dynamic complexity allows structure elucidation of an excited state of KRAS G13D

Localized dynamics of RAS, including regions distal to the nucleotide-binding site, is of high interest for elucidating the mechanisms by which RAS proteins interact with effectors and regulators and for designing inhibitors. Among several oncogenic mutants, methyl relaxation dispersion experiments reveal highly synchronized conformational dynamics in the active (GMPPNP-bound) KRAS G13D , which suggests an exchange between two conformational states in solution. Methyl and 31 P NMR spectra of active KRAS G13D in solution confirm a two-state ensemble interconverting on the millisecond timescale, with a major Pγ atom peak corresponding to the dominant State 1 conformation and a secondary peak indicating an intermediate state different from the known State 2 conformation recognized by RAS effectors. High-resolution crystal structures of active KRAS G13D and KRAS G13D -RAF1 RBD complex provide snapshots of the State 1 and 2 conformations, respectively. We use residual dipolar couplings to solve and cross-validate the structure of the intermediate state of active KRAS G13D , showing a conformation distinct from those of States 1 and 2 outside the known flexible switch regions. The dynamic coupling between the conformational exchange in the effector lobe and the breathing motion in the allosteric lobe is further validated by a secondary mutation in the allosteric lobe, which affects the conformational population equilibrium.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

$\mathcal{N}$ = (1, 0) anomaly multiplet relations in six dimensions

We consider conformal and ’t Hooft anomalies in six-dimensional $\mathcal{N}$ = (1, 0) superconformal field theories, focusing on those conformal anomalies that determine the two- and three-point functions of conserved flavor and SU(2) R currents, as well as stress tensors. By analyzing these correlators in superspace, we explain why the number of independent conformal anomalies is reduced in supersymmetric theories. For instance, non- supersymmetric CFTs in six dimensions have three independent conformal c-anomalies, which determine the stress-tensor two- and three-point functions, but in superconformal theories the three c-anomalies are subject to a linear constraint. We also describe anomaly multiplet relations, which express the conformal anomalies of a superconformal theory in terms of its ’t Hooft anomalies. Following earlier work on the conformal a-anomaly, we argue for these relations by considering the supersymmetric dilaton effective action on the tensor branch of such a theory. We illustrate the utility of these anomaly multiplet relations by presenting exact results for conformal anomalies, and hence current and stress-tensor correlators, in several interacting examples.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2021

Spontaneous rearrangement of acetylated xylan on hydrophilic cellulose surfaces

The interaction of xylan, an abundant plant polysaccharide, with cellulose microfibrils is essential for secondary cell wall strength. A deeper understanding of these interactions is crucial both to improve our understanding of plant cell wall architecture and to design alternate strategies to overcome cellulose recalcitrance for the production of biofuels and sustainable biomaterials. Naturally occurring acetate or glucuronic acid substitutions on xylan have been shown to influence xylan-cellulose interactions. In this work, we use unrestrained molecular dynamics simulations to determine the interactions with the (110) hydrophilic face of cellulose fibers of four different xylans. In the absence of cellulose, all xylans, independent of the substitution pattern, adopt a highly flexible threefold helical screw conformation. However, when xylan is spatially close to a cellulose surface 1,2 linked acetyl xylans (2AcX) adopt rigid twofold helical screw conformations. The 2AcX conformations are primarily stabilized by interactions between the acetylated oxygen and the glycosidic linkage with C-O6 of cellulose. In contrast, the glycosidic oxygens and acetyl decorations for 1,3 linked acetyl groups (3AcX) are oriented away from the cellulose surface and the 3AcX xylans maintain threefold helical screw conformations on the cellulose surface. Our results show that evenly spaced chemical functionalization (with acetyl groups) and the position of substitution (1,2) on xylan backbone play key roles in tuning the xylan-cellulose interactions to stabilize the twofold helical screw conformations of xylan on the cellulose surface. A comparison with previous experimental findings further suggests that 1,2 substitutions induce twofold helical screw conformations of xylan on the cellulose surface irrespective of the chemical nature of the substituent, while 1,3 substitutions primarily bind lignin in threefold helical screw conformations rather than cellulose in plant cell walls.

1,2 Ac↗
DOE OSTI2024

Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation

Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state. To turn off the kinase, protein phosphatases dephosphorylate these sites, but how the conformation of the dynamic activation loop contributes to dephosphorylation was not known. To answer this, we modulated the activation loop conformational equilibrium of human p38α ΜΑP kinase with existing kinase inhibitors that bind and stabilize specific inactive activation loop conformations. From this, we identified three inhibitors that increase the rate of dephosphorylation of the activation loop phospho-threonine by the PPM serine/threonine phosphatase WIP1. Hence, these compounds are “dual-action” inhibitors that simultaneously block the active site and promote p38α dephosphorylation. Our X-ray crystal structures of phosphorylated p38α bound to the dual-action inhibitors reveal a shared flipped conformation of the activation loop with a fully accessible phospho-threonine. In contrast, our X-ray crystal structure of phosphorylated apo human p38α reveals a different activation loop conformation with an inaccessible phospho-threonine, thereby explaining the increased rate of dephosphorylation upon inhibitor binding. These findings reveal a conformational preference of phosphatases for their targets and suggest a unique approach to achieving improved potency and specificity for therapeutic kinase inhibitors.

Science & Technology - Other Topics↗
DOE OSTI2024

Revealing the mechanism of action of a first-in-class covalent inhibitor of $\mathrm{KRASG12C}$ $\mathrm{(ON)}$ and other functional properties of oncogenic $\text{KRAS}$ by 31 P $\mathrm{NMR}$

Individual oncogenic KRAS mutants confer distinct differences in biochemical properties and signaling for reasons that are not well understood. KRAS activity is closely coupled to protein dynamics and is regulated through two interconverting conformations: state 1 (inactive, effector binding deficient) and state 2 (active, effector binding enabled). Here, we use 31 P NMR to delineate the differences in state 1 and state 2 populations present in WT and common KRAS oncogenic mutants (G12C, G12D, G12V, G13D, and Q61L) bound to its natural substrate GTP or a commonly used nonhydrolyzable analog GppNHp (guanosine-5'-[(β,γ)-imido] triphosphate). Our results show that GppNHp-bound proteins exhibit significant state 1 population, whereas GTP-bound KRAS is primarily (90% or more) in state 2 conformation. This observation suggests that the predominance of state 1 shown here and in other studies is related to GppNHp and is most likely nonexistent in cells. We characterize the impact of this differential conformational equilibrium of oncogenic KRAS on RAF1 kinase effector RAS-binding domain and intrinsic hydrolysis. Through a KRAS G12C drug discovery, we have identified a novel small-molecule inhibitor, BBO-8956, which is effective against both GDP- and GTP-bound KRAS G12C. We show that binding of this inhibitor significantly perturbs state 1–state 2 equilibrium and induces an inactive state 1 conformation in GTP-bound KRAS G12C. In the presence of BBO-8956, RAF1–RAS-binding domain is unable to induce a signaling competent state 2 conformation within the ternary complex, demonstrating the mechanism of action for this novel and active-conformation inhibitor.

31P NMR↗
DOE OSTI2021

Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases

The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module (tSH2 module). In the autoinhibited state, this module adopts a conformation that stabilizes an inactive conformation of the kinase domain. The binding of the tSH2 module to phosphorylated immunoreceptor tyrosine-based activation motifs necessitates a conformational change, thereby relieving kinase inhibition and promoting activation. We determined the crystal structure of the isolated tSH2 module of Syk and find, in contrast to ZAP-70, that its conformation more closely resembles that of the peptide-bound state, rather than the autoinhibited state. Hydrogen–deuterium exchange by mass spectrometry, as well as molecular dynamics simulations, reveal that the dynamics of the tSH2 modules of Syk and ZAP-70 differ, with most of these differences occurring in the C-terminal SH2 domain. Our data suggest that the conformational landscapes of the tSH2 modules in Syk and ZAP-70 have been tuned differently, such that the autoinhibited conformation of the Syk tSH2 module is less stable. This feature of Syk likely contributes to its ability to more readily escape autoinhibition when compared to ZAP-70, consistent with tighter control of downstream signaling pathways in T cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

High precision tests of QCD without scale or scheme ambiguities: The 40th anniversary of the Brodsky–Lepage–Mackenzie method

A key issue in making precise predictions in QCD is the uncertainty in setting the renormalization scale μ r and thus determining the correct values of the QCD running coupling α s (μ r ) at each order in the perturbative expansion of a QCD observable. It has often been conventional to simply set the renormalization scale to the typical scale of the process Q and vary it in the range μ r $\in$ [Q/2, 2Q] in order to estimate the theoretical error. This is the practice of Conventional Scale Setting (CSS). The resulting CSS prediction will however depend on the theorist’s choice of renormalization scheme and the resulting pQCD series will diverge factorially. It will also disagree with renormalization scale setting used in QED and electroweak theory thus precluding grand unification. A solution to the renormalization scale-setting problem is offered by the Principle of Maximum Conformality (PMC), which provides a systematic way to eliminate the renormalization scale-and-scheme dependence in perturbative calculations. The PMC method has rigorous theoretical foundations, it satisfies Renormalization Group Invariance (RGI) and preserves all self-consistency conditions derived from the renormalization group. The PMC cancels the renormalon growth, reduces to the Gell-Mann–Low scheme in the N c → 0 Abelian limit and leads to scale- and scheme-invariant results. The PMC has now been successfully applied to many high-energy processes. In this article we summarize recent developments and results in solving the renormalization scale and scheme ambiguities in perturbative QCD. In particular, we present a recently developed method the PMC ∞ and its applications, comparing the results with CSS. The method preserves the property of renormalizable SU(N)/U(1) gauge theories defined as Intrinsic Conformality (iCF). This property underlies the scale invariance of physical observables and leads to a remarkably efficient method to solve the conventional renormalization scale ambiguity at every order in pQCD. This new method reflects the underlying conformal properties displayed by pQCD at NNLO, eliminates the scheme dependence of pQCD predictions and is consistent with the general properties of the PMC. A new method to identify conformal and β-terms, which can be applied either to numerical or to theoretical calculations is also shown. We present results for the thrust and C-parameter distributions in e + e - annihilation showing errors and comparison with the CSS. We also show results for a recent innovative comparison between the CSS and the PMC ∞ applied to the thrust distribution investigating both the QCD conformal window and the QED N c → 0 limit. In order to determine the thrust distribution along the entire renormalization group flow from the highest energies to zero energy, we consider the number of flavors near the upper boundary of the conformal window. In this flavor-number regime the theory develops a perturbative infrared interacting fixed point. These results show that PMC ∞ leads to higher precision and introduces new interesting features in the PMC. In fact, this method preserves with continuity the position of the peak, showing perfect agreement with the experimental data already at NNLO. We also show a detailed comparison of the PMC ∞ with the other PMC approaches: the multi-scale-setting approach (PMCm) and the single-scale-setting approach (PMCs) by comparing their predictions for three important fully integrated quantities R e+e- , R$_Τ$ and Γ (H→$b\bar{b}$) up to the four-loop accuracy.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2022

Poly(cyclosilane) Connectivity Tunes Optical Absorbance

We report herein the influence of skeletal connectivity on the conformation-dependent optical properties of cyclosilane homo- and copolymers. 1,3-Linked cyclosilanes were bathochromically shifted by 20 nm in solution relative to 1,4-linked cyclosilanes, an effect reproduced by quantum chemical calculations on oligomeric model systems. Polysilane optical properties are conformation-dependent, and 1,3-linked cyclosilanes were hypothesized to adopt a favorable conformation unavailable to 1,4-linked cyclosilanes constrained to an endocyclic gauche conformation. Copolymerization of the isomeric cyclosilanes 1,3Si 6 and 1,4Si 6 afforded linear statistical copolymers, as characterized by 1 H and 29 Si NMR spectroscopies. The distinct connectivity of each comonomer was found to give rise to tunable absorption spectra, where the position of the absorption band systematically increased with the increased corporation of 1,3Si 6 . Computational studies pointed to conformation-dependent changes in orbital symmetry in shifting the most intense transition from the low-energy highest occupied molecular orbital (HOMO) → lowest unoccupied molecular orbital (LUMO) transition to a higher-energy HOMO → LUMO + n transition. Here, the results of these studies demonstrate for the first time the role of silicon skeletal connectivity in controlling conformation and optoelectronic properties and provide new insight into the structure-based design of solution-processable silicon-based polymeric materials.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Modeling of Hidden Structures Using Sparse Chemical Shift Data from NMR Relaxation Dispersion

NMR relaxation dispersion measurements report on conformational changes occurring on the μs-ms timescale. Chemical shift information derived from relaxation dispersion can be used to generate structural models of weakly populated alternative conformational states. Current methods to obtain such models rely on determining the signs of chemical shift changes between the conformational states, which are difficult to obtain in many situations. Here, we use a “sample and select” method to generate relevant structural models of alternative conformations of the C-terminal-associated region of Escherichia coli dihydrofolate reductase (DHFR), using only unsigned chemical shift changes for backbone amides and carbonyls ( 1 H, 15 N, and 13 C'). We find that CS-Rosetta sampling with unsigned chemical shift changes generates a diversity of structures that are sufficient to characterize a minor conformational state of the C-terminal region of DHFR. The excited state differs from the ground state by a change in secondary structure, consistent with previous predictions from chemical shift hypersurfaces and validated by the x-ray structure of a partially humanized mutant of E. coli DHFR (N23PP/G51PEKN). The results demonstrate that the combination of fragment modeling with sparse chemical shift data can determine the structure of an alternative conformation of DHFR sampled on the μs-ms timescale. Such methods will be useful for characterizing alternative states, which can potentially be used for in silico drug screening, as well as contributing to understanding the role of minor states in biology and molecular evolution.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Predicting RNA structure and dynamics with deep learning and solution scattering

Advanced deep learning and statistical methods can predict structural models for RNA molecules. However, RNAs are flexible, and it remains difficult to describe their macromolecular conformations in solutions where varying conditions can induce conformational changes. Small-angle x-ray scattering (SAXS) in solution is an efficient technique to validate structural predictions by comparing the experimental SAXS profile with those calculated from predicted structures. There are two main challenges in comparing SAXS profiles to RNA structures: the absence of cations essential for stability and charge neutralization in predicted structures and the inadequacy of a single structure to represent RNA’s conformational plasticity. We introduce a solution conformation predictor for RNA (SCOPER) to address these challenges. This pipeline integrates kinematics-based conformational sampling with the innovative deep learning model, IonNet, designed for predicting Mg 2+ ion binding sites. Validated through benchmarking against 14 experimental data sets, SCOPER significantly improved the quality of SAXS profile fits by including Mg 2+ ions and sampling of conformational plasticity. We observe that an increased content of monovalent and bivalent ions leads to decreased RNA plasticity. Therefore, carefully adjusting the plasticity and ion density is crucial to avoid overfitting experimental SAXS data. SCOPER is an efficient tool for accurately validating the solution state of RNAs given an initial, sufficiently accurate structure and provides the corrected atomistic model, including ions.

59 BASIC BIOLOGICAL SCIENCES↗