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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.

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At least 1,225 records · Page 68
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Mapping the Temperature-dependent and network site-specific onset of spectral diffusion at the surface of a water cluster cage

We explore the kinetic processes that sustain equilibrium in a microscopic, finite system. This is accomplished by monitoring the spontaneous, time-dependent frequency evolution (the frequency autocorrelation) of a single OH oscillator, embedded in a water cluster held in a temperature-controlled ion trap. The measurements are carried out by applying two-color, IR-IR photodissociation mass spectrometry to the D3O+?(HDO)(D2O)19 isotopologue of the “magic number” protonated water cluster, H+?(H2O)21. The OH group can occupy any one of the five spectroscopically distinct sites in the distorted pentagonal dodecahedron cage structure. The OH frequency is observed to evolve over tens of milliseconds in the temperature range (90-120 K). Starting at 100 K, large “jumps” are observed between two OH frequencies separated by ~300 cm-1 indicating migration of the OH group from the bound OH site at 3350 cm-1 to the free position at 3686 cm-1. Increasing the temperature to 110 K leads to partial interconversion among many sites. All sites are observed to interconvert at 120 K such that the distribution of the unique OH group among them adopts the form one would expect for a canonical ensemble. The spectral dynamics displayed by the clusters thus offer an unprecedented view into the molecular-level processes that drive spectral diffusion in an extended network of water molecules.

Yang, Nan↗
DOE OSTI2021

Vascular K ATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides

Vascular tone is dependent on smooth muscle K ATP channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantú syndrome. Unique among K ATP isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular K ATP channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic K ATP channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational “propeller” and “quatrefoil” geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward K ATP channel activation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The Shr receptor from Streptococcus pyogenes uses a cap and release mechanism to acquire heme–iron from human hemoglobin

Streptococcus pyogenes (group A Streptococcus ) is a clinically important microbial pathogen that requires iron in order to proliferate. During infections, S. pyogenes uses the surface displayed Shr receptor to capture human hemoglobin (Hb) and acquires its iron-laden heme molecules. Through a poorly understood mechanism, Shr engages Hb via two structurally unique N-terminal Hb-interacting domains (HID1 and HID2) which facilitate heme transfer to proximal NEAr Transporter (NEAT) domains. Based on the results of X-ray crystallography, small angle X-ray scattering, NMR spectroscopy, native mass spectrometry, and heme transfer experiments, we propose that Shr utilizes a “cap and release” mechanism to gather heme from Hb. In the mechanism, Shr uses the HID1 and HID2 modules to preferentially recognize only heme-loaded forms of Hb by contacting the edges of its protoporphyrin rings. Heme transfer is enabled by significant receptor dynamics within the Shr–Hb complex which function to transiently uncap HID1 from the heme bound to Hb’s β subunit, enabling the gated release of its relatively weakly bound heme molecule and subsequent capture by Shr’s NEAT domains. These dynamics may maximize the efficiency of heme scavenging by S. pyogenes , enabling it to preferentially recognize and remove heme from only heme-loaded forms of Hb that contain iron.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery

G-protein metallochaperone MeaB in bacteria [methylmalonic aciduria type A (MMAA) in humans] is responsible for facilitating the delivery of adenosylcobalamin (AdoCbl) to methylmalonyl-CoA mutase (MCM), the only AdoCbl-dependent enzyme in humans. Genetic defects in the switch III region of MMAA lead to the genetic disorder methylmalonic aciduria in which the body is unable to process certain lipids. Here, we present a crystal structure of Methylobacterium extorquens MeaB bound to a nonhydrolyzable guanosine triphosphate (GTP) analog guanosine-5'-[(β,γ)-methyleno]triphosphate (GMPPCP) with the Cbl-binding domain of its target mutase enzyme (MeMCM cbl ). This structure provides an explanation for the stimulation of the GTP hydrolyase activity of MeaB afforded by target protein binding. We find that upon MCM cbl association, one protomer of the MeaB dimer rotates ~180°, such that the inactive state of MeaB is converted to an active state in which the nucleotide substrate is now surrounded by catalytic residues. Importantly, it is the switch III region that undergoes the largest change, rearranging to make direct contacts with the terminal phosphate of GMPPCP. These structural data additionally provide insights into the molecular basis by which this metallochaperone contributes to AdoCbl delivery without directly binding the cofactor. Our data suggest a model in which GTP-bound MeaB stabilizes a conformation of MCM that is open for AdoCbl insertion, and GTP hydrolysis, as signaled by switch III residues, allows MCM to close and trap its cofactor. Substitutions of switch III residues destabilize the active state of MeaB through loss of protein:nucleotide and protein:protein interactions at the dimer interface, thus uncoupling GTP hydrolysis from AdoCbl delivery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structure of WNT inhibitor adenomatosis polyposis coli down-regulated 1 (APCDD1), a cell-surface lipid-binding protein

Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues, APCDD1 transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed β-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin

Protein translation, one of the most energy-consumptive processes in a eukaryotic cell, requires robust regulation, especially under energy-deprived conditions. A critical component of this regulation is the suppression of translational elongation through reduced ribosome association of the GTPase eukaryotic elongation factor 2 (eEF-2) resulting from its specific phosphorylation by the calmodulin (CaM)-activated α–kinase eEF-2 kinase (eEF-2K). It has been suggested that the eEF-2K response to reduced cellular energy levels is indirect and mediated by the universal energy sensor AMP-activated protein kinase (AMPK) through direct stimulatory phosphorylation and/or downregulation of the eEF-2K-inhibitory nutrient-sensing mTOR pathway. Here, we provide structural, biochemical, and cell-biological evidence of a direct energy-sensing role of eEF-2K through its stimulation by ADP. A crystal structure of the nucleotide-bound complex between CaM and the functional core of eEF-2K phosphorylated at its primary stimulatory site (T348) reveals ADP bound at a unique pocket located on the face opposite that housing the kinase active site. Within this basic pocket (BP), created at the CaM/eEF-2K interface upon complex formation, ADP is stabilized through numerous interactions with both interacting partners. Biochemical analyses using wild-type eEF-2K and specific BP mutants indicate that ADP stabilizes CaM within the active complex, increasing the sensitivity of the kinase to CaM. Induction of energy stress through glycolysis inhibition results in significantly reduced enhancement of phosphorylated eEF-2 levels in cells expressing ADP-binding compromised BP mutants compared to cells expressing wild-type eEF-2K. These results suggest a direct energy-sensing role for eEF-2K through its cooperative interaction with CaM and ADP.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors

The G12D mutation is among the most common KRAS mutations associated with cancer, in particular, pancreatic cancer. Here, we have developed monobodies, small synthetic binding proteins, that are selective to KRAS(G12D) over KRAS(wild type) and other oncogenic KRAS mutations, as well as over the G12D mutation in HRAS and NRAS. Crystallographic studies revealed that, similar to other KRAS mutant-selective inhibitors, the initial monobody bound to the S-II pocket, the groove between switch II and α3 helix, and captured this pocket in the most widely open form reported to date. Unlike other G12D-selective polypeptides reported to date, the monobody used its backbone NH group to directly recognize the side chain of KRAS Asp12, a feature that closely resembles that of a small-molecule inhibitor, MTRX1133. The monobody also directly interacted with H95, a residue not conserved in RAS isoforms. These features rationalize the high selectivity toward the G12D mutant and the KRAS isoform. Structure-guided affinity maturation resulted in monobodies with low nM KD values. Deep mutational scanning of a monobody generated hundreds of functional and nonfunctional single-point mutants, which identified crucial residues for binding and those that contributed to the selectivity toward the GTP- and GDP-bound states. When expressed in cells as genetically encoded reagents, these monobodies engaged selectively with KRAS(G12D) and inhibited KRAS(G12D)-mediated signaling and tumorigenesis. These results further illustrate the plasticity of the S-II pocket, which may be exploited for the design of next-generation KRAS(G12D)-selective inhibitors.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Dinickel enzyme evolved to metabolize the pharmaceutical metformin and its implications for wastewater and human microbiomes

Metformin is the first-line treatment for type II diabetes patients and a pervasive pollutant with more than 180 million kg ingested globally and entering wastewater. The drug’s direct mode of action is currently unknown but is linked to effects on gut microbiomes and may involve specific gut microbial reactions to the drug. In wastewater treatment plants, metformin is known to be transformed by microbes to guanylurea, although genes encoding this metabolism had not been elucidated. In the present study, we revealed the function of two genes responsible for metformin decomposition (mfmA and mfmB) found in isolated bacteria from activated sludge. MfmA and MfmB form an active heterocomplex (MfmAB) and are members of the ureohydrolase protein superfamily with binuclear metal-dependent activity. MfmAB is nickel-dependent and catalyzes the hydrolysis of metformin to dimethylamine and guanylurea with a catalytic efficiency (k cat /K M ) of 9.6 × 10 3 M -1 s -1 and KM for metformin of 0.82 mM. MfmAB shows preferential activity for metformin, being able to discriminate other close substrates by several orders of magnitude. Crystal structures of MfmAB show coordination of binuclear nickel bound in the active site of the MfmA subunit but not MfmB subunits, indicating that MfmA is the active site for the MfmAB complex. Mutagenesis of residues conserved in the MfmA active site revealed those critical to metformin hydrolase activity and its small substrate binding pocket allowed for modeling of bound metformin. In conclusion, this study characterizes the products of the mfmAB genes identified in wastewater treatment plants on three continents, suggesting that metformin hydrolase is widespread globally in wastewater.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Theory of topological exciton insulators and condensates in flat Chern bands

Excitons are the neutral quasiparticles that form when Coulomb interactions create bound states between electrons and holes. Due to their bosonic nature, excitons are expected to condense and exhibit superfluidity at sufficiently low temperatures. In interacting Chern insulators, excitons may inherit the nontrivial topology and quantum geometry from the underlying electron wavefunctions. We theoretically investigate the excitonic bound states and superfluidity in flat-band insulators pumped with light. We find that the exciton wavefunctions exhibit vortex structures in momentum space, with the total vorticity being equal to the difference of Chern numbers between the conduction and valence bands. Moreover, both the exciton binding energy and the exciton superfluid density are proportional to the Brillouin-zone average of the quantum metric and the Coulomb potential energy per unit cell. Spontaneous emission of circularly polarized light from radiative decay is a detectable signature of the exciton vorticity. We propose that the vorticity can also be experimentally measured via the nonlinear anomalous Hall effect, whereas the exciton superfluidity can be detected by voltage-drop quantization through a combination of quantum geometry and Aharonov–Casher effect. Topological excitons and their superfluid phase could be realized in flat bands of twisted Van der Waals heterostructures.

Science & Technology - Other Topics↗
DOE OSTI2025

Structural characterization of influenza group 1 chimeric hemagglutinins as broad vaccine immunogens

Chimeric hemagglutinins (cHA) appear to be promising for the design and development of universal influenza vaccines. Influenza A group 1 cHAs, cH5/1, cH8/1, and cH11/1, comprising an H1 stem attached to either an H5, H8, or H11 globular head, have been used sequentially as vaccine immunogens in human clinical trials and induced high levels of broadly protective antibodies. Using X-ray crystallography and negative-stain electron microscopy, we determined structures of cH5/1, cH8/1, and cH11/1 HAs in their apo (unliganded) and antibody Fab-bound states. Stem-reactive antibodies 3E1 and 31.b.09 recognize their cognate epitopes in cH5/1, cH8/1, and cH11/1 HAs. However, with cH5/1, the head domains are rotated by 35 to 45° around the threefold axis of the HA trimer compared to native HA with a more splayed-open conformation at the stem base. cH11/1 with 3E1 is structurally more native-like but resembles cH5/1 with 31.b.09, whereas cH8/1 with 31.b.09 exhibited a range of closed-to-open stem configurations with some separation of head and stem domains. Furthermore, all of these group 1 cHAs effectively bound a broad head trimer interface antibody and other broad stem antibodies. Thus, the cHAs exhibit structural plasticity without compromising the stem and head trimer interface epitopes for elicitation of influenza A group 1 cross-reactive antibodies.

Science & Technology - Other Topics↗
DOE OSTI2025

Allosteric inhibition of the IZUMO1–JUNO fertilization complex by the naturally occurring antisperm antibody OBF13

Sperm IZUMO1 binds to egg JUNO, and this interaction is essential for mammalian fertilization. Isolated from a female mouse immunized with syngeneic sperm, the antisperm antibody OBF13 recognizes IZUMO1 and inhibits murine fertilization. How OBF13 interferes with sperm–egg interactions was unknown. Here, we present the X-ray crystal structure of IZUMO1 in complex with OBF13. OBF13 binds to the apex of the four-helix domain of IZUMO1, distant from the JUNO-binding site. Our crystal structure of OBF13-bound IZUMO1 resembles apo-IZUMO1 and differs from the structure of IZUMO1 in complex with JUNO. We identify that OBF13 carries a low level of somatic hypermutation, and through deep mutational scanning, we engineer an affinity-enhanced OBF13 variant. This OBF13 variant single-chain fragment variable decreases the apparent affinity of IZUMO1 for membrane-bound murine JUNO and blocks the binding of acrosome-reacted sperm to eggs, thereby preventing fertilization. We propose allostery between the OBF13 epitope and the JUNO-binding site. OBF13 inhibits a conformational change in IZUMO1, preventing fusion-competent sperm from adhering to murine eggs during fertilization. Surprisingly, murine IZUMO1 binds to hamster JUNO with an affinity ~20-fold higher than to murine JUNO. The decreased affinity caused by OBF13 of murine IZUMO1 for hamster JUNO is sufficient for murine sperm to bind to and fuse with hamster eggs. Our studies provide a structural and mechanistic framework for species-specific, allosteric inhibition of IZUMO1 by a naturally occurring antisperm antibody and offer insights into the development of immunocontraceptives.

Science & Technology - Other Topics↗
DOE OSTI2025

Nucleotide- and metalloid-driven conformational changes in the arsenite efflux ATPase ArsA

Arsenite (As III ) is toxic to all organisms due to its ability to tightly bind exposed thiols within cells. An important As III resistance mechanism in prokaryotes involves proteins encoded by thearsoperon. A central component of thearsoperon in many bacteria is the cytoplasmic ATPase, ArsA, which orchestrates a series of nucleotide-dependent handoffs, starting with the capture of As III by the ArsD metallochaperone and culminating in its removal from the cell by the ArsB efflux pump. Although the mechanism of ArsA has been widely studied, the molecular details of how nucleotide hydrolysis modulates these events remain unclear. ArsA is an archetypal member of the intradimeric Walker A (IWA) family of ATPases, implicated in a diversity of complex biological functions. Conformational changes typical of IWA ATPases have been postulated to drive these molecular events but have not been demonstrated. We report cryogenic electron microscopy (cryo-EM) structures of ArsA in MgADP-bound and MgATP-boundopenstates, as well as a distinctclosedMgATP-bound state liganded to As III . X-ray absorption spectroscopy (XAS) confirmed three-coordinate binding of As III to the conserved cysteines at the metalloid-binding site of the closed state. Coupled with biochemical characterization, our cryo-EM structures reveal key conformational changes in the ArsA catalytic cycle consistent with other IWA ATPases and provide the structural basis for allosteric activation of nucleotide hydrolysis by As III . This work establishes how the nucleotide state of ArsA transiently creates a high-affinity binding site that can sequester metalloid within the cell, followed by a nucleotide-driven handoff to ArsB for efflux.

Science & Technology - Other Topics↗
DOE OSTI2025

An unusual Co–S bond links B 12 chaperones in an interprotein complex

Chaperones in trafficking pathways ensure specificity of transition metal loading and protection against adventitious side reactions. In B 12 , an essential cofactor for humans, a cobalt ion is coordinated to a >1.3 kDa tetrapyrrolic scaffold, posing logistical challenges for its translocation. In this study, we report the 3.4 Å crystal structure of the human MMACHC and MMADHC B 12 chaperones, tethered via a rarely seen covalent cobalt–sulfur bond. B 12 is bound in the base-off state to MMACHC, with Cys-261 on MMADHC serving as the upper axial ligand; the lower-axial position is vacant. The propensity of thiolato-cobalamin derivatives bound to MMACHC to undergo spontaneous decomposition via general acid catalysis or reduction/oxidation chemistry is averted in the interprotein complex with MMADHC. An exposed face in the complex suggests an exit route for B 12 . No known clinical variants localize to the interprotein interface, consistent with the cobalt–sulfur bond being key to forming the high-affinity complex.

Science & Technology - Other Topics↗
DOE OSTI2020

Rational design, synthesis, and evaluation of uncharged, “smart” bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase

Organophosphate (OP) intoxications from nerve agent and OP pesticide exposures are managed with pyridinium aldoxime–based therapies whose success rates are currently limited. The pyridinium cation hampers uptake of OPs into the central nervous system (CNS). Furthermore, it frequently binds to aromatic residues of OP-inhibited acetylcholinesterase (AChE) in orientations that are nonproductive for AChE reactivation, and the structural diversity of OPs impedes efficient reactivation. Improvements of OP antidotes need to include much better access of AChE reactivators to the CNS and optimized orientation of the antidotes' nucleophile within the AChE active-center gorge. On the basis of X-ray structures of a CNS-penetrating reactivator, monoxime RS194B, reversibly bound to native and venomous agent X (VX)–inhibited human AChE, here we created seven uncharged acetamido bis-oximes as candidate antidotes. Both oxime groups in these bis-oximes were attached to the same central, saturated heterocyclic core. Diverse protonation of the heterocyclic amines and oxime groups of the bis-oximes resulted in equilibration among up to 16 distinct ionization forms, including uncharged forms capable of diffusing into the CNS and multiple zwitterionic forms optimal for reactivation reactions. Conformationally diverse zwitterions that could act as structural antidote variants significantly improved in vitro reactivation of diverse OP-human AChE conjugates. Oxime group reorientation of one of the bis-oximes, forcing it to point into the active center for reactivation, was confirmed by X-ray structural analysis. Finally, our findings provide detailed structure-activity properties of several CNS-directed, uncharged aliphatic bis-oximes holding promise for use as protonation-dependent, conformationally adaptive, “smart” accelerated antidotes against OP toxicity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Gamma Radiolysis of Phenyl-Substituted TODGAs: Part I

The radiolytic stabilities of three phenylated analogs of N,N,N’,N’-tetraoctyl diglycolamide (TODGA) were investigated: 2-(2-(di-n-octylamino)-2-oxoethoxy)-N,N-di-n-octyl-2-phenylacetamide (PhTODGA), which has a phenyl substituent bound to a central methylene, 2-(2-(di-n-octylamino)-2-oxo-1-phenylethoxy)-N,N-di-n-octylpropanamide (PhMeTODGA), which also contains a methyl substituent bound to the methylene on the other side of the ether moiety, and, 2-(2-N-n-hexyl-N-phenylamino)-2-oxoethoxy)-N-n-hexyl-N-phenylacetamide (DHDPDGA), which has phenyl substituents located on the amide groups instead of the central methylenes. The objective of Part I of this series of papers covers was to evaluate the contribution of the phenyl group to the radiolytic stability of these diglycolamides when irradiated in a) n-dodecane, and b) n-dodecane in the presence of a nitric acid-containing aqueous phase. The results indicate that the presence of the phenyl group decreases the overall radiolytic stability compared to unsubstituted TODGA. However, the results also indicate that the phenyl groups interact with nitric acid in a cooperative fashion that enhances the radiation stability of the phenylated diglycolamide (DGA) derivatives in the presence of a nitric acid-containing aqueous phase compared to irradiation in only n-dodecane. So, the results are consistent with the hypothesized formation of nitric acid-phenylated DGA complexes in the n-dodecane phase that are significantly more stable with respect to gamma irradiation, compared to the phenylated DGA molecules alone.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2023

Gamma Radiolysis of Phenyl-Substituted TODGAs: Part II

The radiolytic degradation chemistry of three phenylated analogs of $N,N,N’,N’$-tetraoctyl diglycolamide (TODGA) was investigated: 2-(2-(di-$n$-octylamino)-2-oxoethoxy)-$N,N$-di-$n$-octyl-2-phenylacetamide (PhTODGA), which has a phenyl substituent bound to a central methylene, 2-(2-(di-$n$-octylamino)-2-oxo-1-phenylethoxy)-$N,N$-di-$n$-octylpropanamide (PhMeTODGA), which also contains a methyl substituent bound to the methylene on the other side of the ether moiety, and, 2-(2-$N$-$n$-hexyl-$N$-phenylamino)-2-oxoethoxy)-$N$-$n$-hexyl-$N$-phenylacetamide (DHDPDGA), which has phenyl substituents located on the amide groups instead of the central methylenes. In Part II of this series of papers radiolytic degradation products were identified after separation with liquid chromatography by High Resolution, Accurate-Mass mass spectrometry and collision-induced dissociation. At least twenty-two radiolytic degradation products were identified for PhTODGA, twenty-nine for PhMeTODGA, and over three dozen for DHDPDGA. The suite of radiolytic degradation products of these three investigated ligands was significantly larger than has been reported for previously studied diglycolamides, owing to their asymmetric nature, and to the identification of several new degradation mechanisms, including addition of methyl, hydroxyl, and nitrogen oxide radicals, that have not been previously reported for diglycolamides. Degradation products that contained addition of a NO 2 or NO 3 group were particularly prevalent for DHDPDGA, likely due to the phenyl side-groups. In conclusion, several of these newly observed mechanisms do not appear to depend on the presence of the phenyl groups, suggesting these novel mechanisms may apply to other diglycolamides.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2026

Augmenting subspace optimization methods with linear bandits

In this work, we consider the framework of methods for unconstrained minimization that are, in each iteration, restricted to a model that is only a valid approximation to the objective function on some affine subspace containing an incumbent point. These methods are of practical interest in computational settings where derivative information is either expensive or impossible to obtain. Recent attention has been paid in the literature to employing randomized matrix sketching for generating the affine subspaces within this framework. We consider a relatively straightforward, deterministic augmentation of such a generic subspace optimization method. In particular, we consider a sequential optimization framework where actions consist of one-dimensional linear subspaces and rewards consist of (approximations to) the magnitudes of directional derivatives computed in the direction of the action subspace. Reward maximization in this context is consistent with maximizing lower bounds on descent guaranteed by first-order Taylor models. This sequential optimization problem can be analysed through the lens of dynamic regret. We modify an existing linear upper confidence bound (UCB) bandit method and prove sublinear dynamic regret in the subspace optimization setting. We demonstrate the efficacy of employing this linear UCB method in a setting where forward-mode algorithmic differentiation can provide directional derivatives in arbitrary directions and in a derivative-free setting. For the derivative-free setting, we propose SS-POUNDers, an extension of the derivative-free optimization method POUNDers that employs the linear UCB mechanism to identify promising subspaces. Our numerical experiments suggest a preference, in either computational setting, for employing a linear UCB mechanism within a subspace optimization method.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Microstate distinguishability, quantum complexity, and the eigenstate thermalization hypothesis

In this work, we use quantum complexity theory to quantify the difficulty of distinguishing eigenstates obeying the eigenstate thermalization hypothesis (ETH). After identifying simple operators with an algebra of low-energy observables and tracing out the complementary high-energy Hilbert space, the ETH leads to an exponential suppression of trace distance between the coarse grained eigenstates. Conversely, we show that an exponential hardness of distinguishing between states implies ETH-like matrix elements. Finally, the BBBV lower bound on the query complexity of Grover search then translates directly into a complexity-theoretic statement lower bounding the hardness of distinguishing these reduced states

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗