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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 127 records · Page 7

Rapid Brownian Motion Primes Ultrafast Reconstruction of Intrinsically Disordered Phe-Gly Repeats Inside the Nuclear Pore Complex

Conformational behavior of intrinsically disordered proteins, such as Phe-Gly repeat domains, alters drastically when they are confined in, and tethered to, nan channels. This has challenged our understanding of how they serve to selectively facilitate translocation of nuclear transport receptor (NTR)-bearing macromolecules. Heterogeneous FG-repeats, tethered to the NPC interior, nonuniformly fill the channel in a diameter-dependent manner and adopt a rapid Brownian motion, thereby forming a porous and highly dynamic polymeric meshwork that percolates in radial and axial directions and features two distinguishable zones: a dense hydrophobic rod-like zone located in the center, and a peripheral low-density shell-like zone. The FG-meshwork is locally disrupted upon interacting with NTR-bearing macromolecules, but immediately reconstructs itself between 0.44μs and 7.0μs, depending on cargo size and shape. This confers a perpetually-sealed state to the NPC, and is solely due to rapid Brownian motion of FG-repeats, not FGrepeat hydrophobic bonds. Elongated-shaped macromolecules, both in the presence and absence of NTRs, penetrate more readily into the FG-meshwork compared to their globular counterparts of identical volume and surface chemistry, highlighting the importance of the shape effects in nucleocytoplasmic transport. These results can help our understanding of geometrical effects in, and the design of, intelligent and responsive biopolymer-based materials in nanofiltration and artificial nanopores.

59 BASIC BIOLOGICAL SCIENCES↗

Repeat variation in the human PER2 gene as a new genetic marker associated with cocaine addiction and brain dopamine D2 receptor availability

Low dopamine D2 receptor (D2R) levels in the striatum are consistently reported in cocaine abusers; inter-individual variations in the degree of the decrease suggest a modulating effect of genetic makeup on vulnerability to addiction. The PER2 (Period 2) gene belongs to the clock genes family of circadian regulators; circadian oscillations of PER2 expression in the striatum was modulated by dopamine through D2Rs. Aberrant periodicity of PER2 contributes to the incidence and severity of various brain disorders, including drug addiction. Here we report a newly identified variable number tandem repeat (VNTR) polymorphism in the human PER2 gene (VNTR in the third intron). We found significant differences in the VNTR alleles prevalence across ethnic groups so that the major allele (4 repeats (4R)) is over-represented in non-African population (4R homozygosity is 88%), but not in African Americans (homozygosity 51%). We also detected a biased PER2 genotype distribution among healthy controls and cocaine addicted individuals. In African Americans, the proportion of 4R/three repeat (3R) carriers in healthy controls is much lower than that in cocaine abusers (23% vs 39%, P ¼ 0.004), whereas among non-Africans most 3R/4R heterozygotes are healthy controls (10.5% vs 2.5%, P ¼ 0.04). Analysis of striatal D2R availability measured with positron emission tomography and [11C]raclopride revealed higher levels of D2R in carriers of 4R/4R genotype (Po0.01). Taken together, these results provide preliminary evidence for the role of the PER2 gene in regulating striatal D2R availability in the human brain and in vulnerability for cocaine addiction.

60 APPLIED LIFE SCIENCES↗

Method to improve the repeatability of dynamic contact resistance measurement test results for high-voltage circuit breakers

Dynamic contact resistance measurement (DRM) is an effective technique to evaluate the contact condition in substations without dismantling circuit breakers. However, performing DRM tests with unsuitable test parameters will cause low repeatability of the test results, and even lead to the misdiagnosis of contact condition. Performing the DRM tests at high DC injected current can improve the repeatability. This paper studies the mechanism of the DC injected current on the repeatability of the DRM test results, and it also promotes a new determination method of the DC injected current amplitude. The impact of the DC injected current on DRM test results is reviewed. The mechanism of the DC injected current on DRM test results is investigated by analysing the chemical composition of the contact surface, the force exerted on the contacts, and the temperatures of a-spots on the contacts' surface. Results indicate that not the Lorentz force, but the temperature of a-spots is the primary influencing factor. The amplitude of the DC injected current can be determined by calculating the temperatures of the a-spot on the contacts' surface. And this method can also be used for other SF6 circuit breakers.

Cheng, Tingting↗

The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats

On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. But, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform, glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. In order to obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We also found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC. Collectively, these results provide information about glutaminases that may aid in the design of isoform-specific glutaminase inhibitors.

59 BASIC BIOLOGICAL SCIENCES↗

Structure of native four-repeat satellite III sequence with non-canonical base interactions

Abstract Tandem-repetitive DNA (where two or more DNA bases are repeated numerous times) can adopt non-canonical secondary structures. Many of these structures are implicated in important biological processes. Human Satellite III (HSat3) is enriched for tandem repeats of the sequence ATGGA and is located in pericentromeric heterochromatin in many human chromosomes. Here, we investigate the secondary structure of the four-repeat HSat3 sequence 5′-ATGGA ATGGA ATGGA ATGGA-3′ using X-ray crystallography, NMR, and biophysical methods. Circular dichroism spectroscopy, thermal stability, native PAGE, and analytical ultracentrifugation indicate that this sequence folds into a monomolecular hairpin with non-canonical base pairing and B-DNA characteristics at concentrations below 0.9 mM. NMR studies at 0.05–0.5 mM indicate that the hairpin is likely folded-over into a compact structure with high dynamics. Crystallographic studies at 2.5 mM reveal an antiparallel self-complementary duplex with the same base pairing as in the hairpin, extended into an infinite polymer. The non-canonical base pairing includes a G–G intercalation sandwiched by sheared A–G base pairs, leading to a cross-strand four guanine stack, so called guanine zipper. The guanine zippers are spaced throughout the structure by A–T/T–A base pairs. Our findings lend further insight into recurring structural motifs associated with the HSat3 and their potential biological functions.

59 BASIC BIOLOGICAL SCIENCES↗

Efficient quantum repeater based on deterministic Rydberg gates

We propose an efficient quantum repeater architecture with mesoscopic atomic ensembles, where the Rydberg blockade is employed for deterministic local entanglement generation, entanglement swapping, and entanglement purification. Compared to a conventional atomic-ensemble-based quantum repeater, the entanglement distribution rate is improved by up to two orders of magnitude with the help of the deterministic Rydberg gate. This quantum repeater scheme is robust and fast, and thus opens up a way for practical long-distance quantum communication.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Rate analysis for a hybrid quantum repeater

We present a detailed rate analysis for a hybrid quantum repeater assuming perfect memories and using optimal probabilistic entanglement generation and deterministic swapping routines. The hybrid quantum repeater protocol is based on atomic qubit-entanglement distribution through optical coherent-state communication. An exact, analytical formula for the rates of entanglement generation in quantum repeaters is derived, including a study on the impacts of entanglement purification and multiplexing strategies. More specifically, we consider scenarios with as little purification as possible and we show that for sufficiently low local losses, such purifications are still more powerful than multiplexing. In a possible experimental scenario, our hybrid system can create near-maximally entangled (F=0.98) pairs over a distance of 1280 km at rates of the order of 100 Hz.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Quantum repeaters based on deterministic storage of a single photon in distant atomic ensembles

Quantum repeaters hold the promise to prevent the photon losses in communication channels. Most recently, the serious efforts have been applied to achieve scalable distribution of entanglement over long distances. However, the probabilistic nature of entanglement generation and realistic quantum memory storage times make the implementation of quantum repeaters an outstanding experimental challenge. We propose a quantum repeater protocol based on the deterministic storage of a single photon in atomic ensembles confined in distant high-finesse cavities and show that this system is capable of distributing the entanglement over long distances with a much higher rate as compared to previous protocols, thereby alleviating the limitations on the quantum memory lifetime by several orders of magnitude. Our scheme is robust with respect to phase fluctuations in the quantum channel, while the fidelity imperfection is fixed and negligibly small at each step of entanglement swapping.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Searching for gravitational waves with strongly lensed repeating fast radio bursts

We report that since their serendipitous discovery, fast radio bursts (FRBs) have garnered a great deal of attention from both observers and theorists. A new class of radio telescopes with wide fields of view have enabled a rapid accumulation of FRB observations, confirming that FRBs originate from cosmological distances. The high occurrence rate of FRBs and the development of new instruments to observe them create opportunities for FRBs to be utilized for a host of astrophysical and cosmological studies. We focus on the rare, and as yet undetected, subset of FRBs that undergo repeated bursts and are strongly gravitationally lensed by intervening structure. An extremely precise timing of burst arrival times is possible for strongly lensed repeating FRBs, and we show how this timing precision enables the search for long-wavelength gravitational waves, including those sourced by supermassive black hole binary systems. The timing of burst arrival for strongly lensed repeating FRBs is sensitive to gravitational-wave sources near the FRB host galaxy, which may lie at cosmological distances and would therefore be extremely challenging to detect by other means. Timing of strongly lensed FRBs can also be combined with pulsar timing array data to search for correlated time delays characteristic of gravitational waves passing through the Earth.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Repeated gravitational wave bursts from cosmic strings

A characteristic observational signature of cosmic strings are short duration gravitational wave (GW) bursts. These have been searched for by the LIGO-Virgo-KAGRA (LVK) Collaboration and will be searched for with LISA. We point out that these burst signals are repeated, since cosmic string loops evolve quasiperiodically in time, and will always appear from essentially the same position in the sky. We estimate the number of GW repeaters for LVK and LISA and show that the string tension that can be probed scales as detector sensitivity to the sixth power, which raises hope for detection in future GW detectors. Furthermore, the observation of repeated GW bursts from the same cosmic string loop helps distinguish between the GW waveform parameters and the sky localization.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Modifying Network Guided Vehicle for Repeatable EcoCAR ACC Energy Testing

The newest iteration of the Department of Energy (DOE) Advanced Vehicle Technology Competitions is the EcoCAR Mobility Challenge. In this paper, ANL and HORIBA MIRA collaborate to propose and pilot a test method that enables controlled, repeatable track-based energy consumption testing of semi-autonomous features. The testing was performed at MIRA’s proving ground facility in Nuneaton, UK, using their Network Guided Vehicle (NGV) connectivity and automation test platform. The NGV served as a repeatable lead vehicle following prescribed drive traces around two different track circuits while the host vehicle under test, a Honda Civic with full speed range Adaptive Cruise Control, followed behind. Over the course of a two day test, multiple iterations of certification and custom EPA drive traces were performed on track, demonstrating the viability of a two vehicle energy test. Results were analyzed to assess NGV lead vehicle performance in following the prescribed cycle using SAE J2951 standard calculations in an effort to quantify how repeatably and accurately the lead vehicle followed the trace. Host vehicle energy consumption was assessed using both vehicle CAN bus monitoring and an on-board fuel flow meter.

ACC↗

SU-E-J-263: Repeatability of SUV and Texture Parameters in Serial PET Studies

Purpose: Standardized uptake values (SUV) are standard quantitative PET measures of FDG tumor uptake used,and are used as a tool to monitor response to therapy. Textural analysis is emerging as a new tool for assessing intratumoral heterogeneity which may allow better tissue characterization and improved prediction of response and survival rate.Understanding what variations may be expected in these parameters is key in order to make decisions based on how the change throughout the course of treatment. The aim of this study was to assess repeatability in SUV measures and texture parameters,and establish criteria that differentiate changes associated with treatment rather than statistical variability. Methods: Eighty patients,167 random lesions total,were scanned in a GE Discovery STE PET/CT Scanner. One field-of-view was chosen centered on the largest lesion observed in a clinical whole-body FDG PET.Immediately following,a gated 9 min scan was acquired in list mode,without changing the patient’s position between any scans. Data was replayed into 3 time bins,3 min each,in order to insure equivalent noise characteristics in each replicate.Data was reconstructed into 128×128×47 square matrices.One VOI was drawn over each lesion for each patient and used to segment all 3 replicates. The mean.max and peak SUV were calculated for each VOI and replicate. First-order textural features were also calculated (skewness and kurtosis). Repeatability was calculated as the average standard deviation over the mean for the 3 repeated measurements for each lesion. Results: The average percent error in the SUV max,peak and mean were 3.4%(0– 12.9%),1.9% (0–7.5%),2.8% (0–12.2%),respectively.For skewness and kurtosis they were 10.9% and 17.8%. Conclusion: We have shown that there is a large variation in %error in SUV measures across patients. SUVpeak is the least variable and kurtosis and skewness parameters are less reliable thatn SUVs.Higher order textures are be.

60 APPLIED LIFE SCIENCES↗

SU-E-T-764: Track Repeating Algorithm for Proton Therapy Applied to Intensity Modulated Proton Therapy for Head-And-Neck Patients

Purpose: To determine the suitability of fast Monte Carlo techniques for dose calculation in particle therapy based on track-repeating algorithm for Intensity Modulated Proton Therapy, IMPT. The application of this technique will make possible detailed retrospective studies of large cohort of patients, which may lead to a better determination of Relative Biological Effects from the analysis of patient data. Methods: A cohort of six head-and-neck patients treated at the University of Texas MD Anderson Cancer Center with IMPT were utilized. The dose distributions were calculated with the standard Treatment Plan System, TPS, MCNPX, GEANT4 and FDC, a fast track-repeating algorithm for proton therapy for the verification and the patient plans. FDC is based on a GEANT4 database of trajectories of protons in a water. The obtained dose distributions were compared to each other utilizing the g-index criteria for 3mm-3% and 2mm-2%, for the maximum spatial and dose differences. The γ-index was calculated for voxels with a dose at least 10% of the maximum delivered dose. Dose Volume Histograms are also calculated for the various dose distributions. Results: Good agreement between GEANT4 and FDC is found with less than 1% of the voxels with a γ-index larger than 1 for 2 mm-2%. The agreement between MCNPX with FDC is within the requirements of clinical standards, even though it is slightly worse than the comparison with GEANT4.The comparison with TPS yielded larger differences, what is also to be expected because pencil beam algorithm do not always performed well in highly inhomogeneous areas like head-and-neck. Conclusion: The good agreement between a track-repeating algorithm and a full Monte Carlo for a large cohort of patients and a challenging, site like head-and-neck, opens the path to systematic and detailed studies of large cohorts, which may yield better understanding of biological effects.

60 APPLIED LIFE SCIENCES↗

SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ({sup 1}H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo {sup 1}H MRS. Methods: We used high-field {sup 1}H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

60 APPLIED LIFE SCIENCES↗

Rapid quantification of sequence repeats to resolve the size, structure and contents of bacterial genomes

Background: The numerous classes of repeats often impede the assembly of genome sequences from the short reads provided by new sequencing technologies. We demonstrate a simple and rapid means to ascertain the repeat structure and total size of a bacterial or archaeal genome without the need for assembly by directly analyzing the abundances of distinct k-mers among reads. Results: The sensitivity of this procedure to resolve variation within a bacterial species is demonstrated: genome sizes and repeat structure of five environmental strains of E. coli from short Illumina reads were estimated by this method, and total genome sizes corresponded well with those obtained for the same strains by pulsed-field gel electrophoresis. In addition, this approach was applied to read-sets for completed genomes and shown to be accurate over a wide range of microbial genome sizes. Conclusions: Application of these procedures, based solely on k-mer abundances in short read data sets, allows aspects of genome structure to be resolved that are not apparent from conventional short read assemblies. This knowledge of the repetitive content of genomes provides insights into genome evolution and diversity.

59 BASIC BIOLOGICAL SCIENCES↗

Comparative Genome Analysis Reveals an Absence of Leucine-Rich Repeat Pattern-Recognition Receptor Proteins in the Kingdom Fungi</strong

In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants. The absence of pattern recognition receptors suggests that fungi may possess novel classes of pattern recognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence of the osmotrophic growth form.

59 BASIC BIOLOGICAL SCIENCES↗

DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases

Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.

59 BASIC BIOLOGICAL SCIENCES↗

Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

08 HYDROGEN↗