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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure

Abstract INTRODUCTION Successful cognitive aging is related to both maintaining brain structure and avoiding Alzheimer's disease (AD) pathology, but how these factors interplay is unclear. METHODS A total of 109 cognitively normal older adults (70+ years old) underwent amyloid beta (Aβ) and tau positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and cognitive testing. Cognitive aging was quantified using the cognitive age gap (CAG), subtracting chronological age from predicted cognitive age. RESULTS Lower CAG (younger cognitive age) was related to slower decline in episodic memory, multi‐domain cognition, and atrophy of the midcingulate cortex (MCC). Lower entorhinal cortical tau was linked to slower decline in episodic memory, multi‐domain cognition, and hippocampal atrophy. DISCUSSION These results suggest that aging outcomes may be influenced by two independent pathways: one associated with tau accumulation, affecting primarily memory and hippocampal atrophy, and another involving tau‐independent structural preservation of the MCC, benefiting multi‐domain cognition over time. Highlights Younger cognitive age (lower cognitive age gap [CAG]) is related to slower cognitive decline. Lower CAG is linked to slower midcingulate cortex (MCC) atrophy. Reduced tau in the entorhinal cortex is related to less hippocampal atrophy and cognitive decline. Structural preservation of the MCC benefits multi‐domain cognition over time. Two independent pathways influence cognitive aging: tau accumulation and MCC preservation.

Neurosciences & Neurology↗
NASA NTRS1994

GRIS background reduction results using isotopically enriched Ge

The Gamma Ray Imaging Spectrometer (GRIS) was flown twice from Alice Springs, Australia, in the spring of 1992 for a total of 32 hr at float altitude. One of the seven Ge detectors was isotopically enriched (greater than 97% Ge-70). This was the first time an enriched-Ge detector was used for astrophysical observations. Because of its thick anticoincidence shield, the GRIS instrument background is dominated by internal beta-decay in the energy range of 200-1000 keV. Half of the contribution in this beta-decay 'hump' is due to neutron-activated Ge-74. In this energy range, GRIS observed a factor of 2 reduction in the background in the enriched detector, as predicted. In future instruments (e.g., INTEGRAL), with thicker anticoincidence shields and smaller apertures, the background reduction will be even larger. Three strong instrumental background lines (54, 67, and 139 keV) are also eliminated. The elimination of the first two is particularly important for cylotron line observations.

Barthelmy, S. D.↗
DOE OSTI2013

Proton form factor ratio, μ p G E P /G M P from double spin asymmetry

The form factors are fundamental properties of the nucleon representing the effect of its structure on its response to electromagnetic probes such as electrons. They are functions of the four-momentum transfer squared Q 2 between the electron and the proton. This thesis reports the results of a new measurement of the ratio of the electric and magnetic form factors of the proton up to Q 2 = 5.66 (GeV/c) 2 using the double spin asymmetry with a polarized beam and target. Experiment E07-003 (SANE, Spin Asymmetries of the Nucleon Experiment) was carried out in Hall C at Jefferson Lab in 2009 to study the proton spin structure functions with a dynamically polarized ammonia target and longitudinally polarized electron beam. By detecting elastically scattered protons in the High-Momentum Spectrometer (HMS) in coincidence with the electrons in the Big Electron Telescope Array (BETA), elastic measurements were carried out in parallel. The elastic double spin asymmetry allows one to extract the proton electric to magnetic form factor ratio G p E /G p M at high-momentum transfer, Q 2 = 5.66 (GeV/c) 2 . In addition to the coincidence data, inclusively scattered electrons from the polarized ammonia target were detected by HMS, which allows to measure the beam-target asymmetry in the elastic region with the target spin nearly perpendicular to the momentum transfer, and to extract G p E /G p M at low Q 2 = 2.06 (GeV/c) 2 . This alternative measurement of G p E /G p M has verified and confirmed the dramatic discrepancy at high Q 2 between the Rosenbluth and the recoil-polarization-transfer iv method with a different measurement technique and systematic uncertainties uncorrelated to those of the recoil-polarization measurements. The measurement of the form factor ratio at Q 2 = 2.06 (GeV/c) 2 has been determined as {mu}{sub p}G p E /G p M = 0.605{+-}0.178 stat {+-}0.033 sys which is in agreement with an earlier measurement with the polarized target technique at similar kinematics. The measurement of the form factor ratio at Q 2 = 5.66 (GeV/c) 2 has been determined as μ p G p E /G p M = 0.672 {+-} 0.362 stat which represents the highest Q 2 reach with the double spin asymmetry to date.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2012

Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Wnt signaling and colon tumorigenesis - A view from the periphery

In this brief overview we discuss the association between Wnt signaling and colon cell biology and tumorigenesis. Our current understanding of the role of Apc in the {beta}-catenin destruction complex is compared with potential roles for Apc in cell adhesion and migration. The requirement for phosphorylation in the proteasomal-mediated degradation of {beta}-catenin is contrasted with roles for phospho-{beta}-catenin in the activation of transcription, cell adhesion and migration. The synergy between Myb and {beta}-catenin regulation of transcription in crypt stem cells during Wnt signaling is discussed. Finally, potential effects of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis, stem cell localization and crypt fission are considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

INSTABILITY OF MAGNETIZED IONIZATION FRONTS SURROUNDING H II REGIONS

An ionization front (IF) surrounding an H II region is a sharp interface where a cold neutral gas makes the transition to a warm ionized phase by absorbing UV photons from central stars. We investigate the instability of a plane-parallel D-type IF threaded by parallel magnetic fields, by neglecting the effects of recombination within the ionized gas. We find that weak D-type IFs always have the post-IF magnetosonic Mach number M{sub M2}≤1. For such fronts, magnetic fields increase the maximum propagation speed of the IFs, while reducing the expansion factor α by a factor of 1 + 1/(2β{sub 1}) compared to the unmagnetized case, with β{sub 1} denoting the plasma beta in the pre-IF region. IFs become unstable to distortional perturbations owing to gas expansion across the fronts, exactly analogous to the Darrieus-Landau instability of ablation fronts in terrestrial flames. The growth rate of the IF instability is proportional linearly to the perturbation wavenumber, as well as the upstream flow speed, and approximately to α{sup 1/2}. The IF instability is stabilized by gas compressibility and becomes completely quenched when the front is D-critical. The instability is also stabilized by magnetic pressure when the perturbations propagate in the direction perpendicular to the fields. When the perturbations propagate in the direction parallel to the fields, on the other hand, it is magnetic tension that reduces the growth rate, completely suppressing the instability when M{sub M2}{sup 2}<2/(2β{sub 1}−1). When the front experiences an acceleration, the IF instability cooperates with the Rayleigh-Taylor instability to make the front more unstable.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

Instabilities driven by the fundamental crabbing mode

The Electron Ion Collider (EIC) requires crab cavities to correct for crossing angle effects. These cavities produce a time varying horizontal kick that makes the collision head on in the center of mass frame of the bunches. This results in a luminosity that is very close to the the luminosity obtained without a crossing angle. Producing the kick requires a transverse RF field. This field requires a superconducting resonator and reasonable power levels require loaded quality factors of order a million. This results is a very large transverse impedance for the crabbing mode. The horizontal beta function is large and this, coupled with the large transverse impedance of the resonator can lead to strong instabilities. In the first section of the paper a simple model is used to describe the situation without feedback. There are large ranges of tune leading to strong instabilities in both the electron and hadron storage rings of the EIC. These estimates are confirmed with simulations. In the second section, RF feedback is used to reduce the apparent impedance of the crabbing mode. Simulating the actual feedback would require both a significant rewrite of the tracking code and a significant reduction in computational speed. Instead, the apparent impedance is fitted using one pole filters, which allows use of the existing simulation code. In the third section a transverse damping system is outlined.

43 PARTICLE ACCELERATORS↗
NASA NTRS1980

The effect of preparation conditions on the structure and mechanical properties of reaction-sintered silicon nitride

The microstructure of reaction sintered silicon nitride (RSSN) was changed over a wide range by varying the grain density, grain size of the silicon starting powder, nitriding conditions, and by introducing artificial pores. The influence of single microstructural parameters on mechanical properties like room temperature strength, creep behavior, and resistance to thermal shock was investigated. The essential factors influencing these properties were found to be total porosity, pore size distribution, and the fractions of alpha and beta Si3N4. In view of high temperature engineering applications of RSSN, potentials for optimizing the material's properties by controlled processing are discussed.

Heinrich, J.↗
DOE OSTI2012

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Recent progress on spherical torus research

The spherical torus or spherical tokamak (ST) is a member of the tokamak family with its aspect ratio (A = R{sub 0}/a) reduced to A ∼ 1.5, well below the normal tokamak operating range of A ≥ 2.5. As the aspect ratio is reduced, the ideal tokamak beta β (radio of plasma to magnetic pressure) stability limit increases rapidly, approximately as β ∼ 1/A. The plasma current it can sustain for a given edge safety factor q-95 also increases rapidly. Because of the above, as well as the natural elongation κ, which makes its plasma shape appear spherical, the ST configuration can yield exceptionally high tokamak performance in a compact geometry. Due to its compactness and high performance, the ST configuration has various near term applications, including a compact fusion neutron source with low tritium consumption, in addition to its longer term goal of an attractive fusion energy power source. Since the start of the two mega-ampere class ST facilities in 2000, the National Spherical Torus Experiment in the United States and Mega Ampere Spherical Tokamak in UK, active ST research has been conducted worldwide. More than 16 ST research facilities operating during this period have achieved remarkable advances in all fusion science areas, involving fundamental fusion energy science as well as innovation. These results suggest exciting future prospects for ST research both near term and longer term. The present paper reviews the scientific progress made by the worldwide ST research community during this new mega-ampere-ST era.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2016

First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment

The NEXT experiment aims to observe the neutrinoless double beta decay of xenon in a high-pressure 136 Xe gas TPC using electroluminescence (EL) to amplify the signal from ionization. One of the main advantages of this technology is the possibility to reconstruct the topology of events with energies close to Q ββ . This paper presents the first demonstration that the topology provides extra handles to reject background events using data obtained with the NEXT-DEMO prototype. Single electrons resulting from the interactions of 22 Na 1275 keV gammas and electron-positron pairs produced by conversions of gammas from the 228 Th decay chain were used to represent the background and the signal in a double beta decay. Furthermore, these data were used to develop algorithms for the reconstruction of tracks and the identification of the energy deposited at the end-points, providing an extra background rejection factor of 24.3 ± 1.4 (stat.)%, while maintaining an efficiency of 66.7 ± 1% for signal events.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2015

Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids

Although classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl beta-diol, phthiocerol, with branched-chain fatty acids know as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. We here show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl beta-diol substrate analogues. Applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinase PknB modifies PapA5 on three Thr residues, including two (T196, T198) located on an unresolved loop. These results clarify the DIM biosynthetic pathway and suggest possible mechanisms by which DIM biosynthesis may be regulated by the post-translational modification of PapA5.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2018

Surface background suppression in liquid argon dark matter detectors using a newly discovered time component of tetraphenyl-butadiene scintillation

Here, decays of radioisotopes on inner detector surfaces can pose a major background concern for the direct detection of dark matter. While these backgrounds are conventionally mitigated with position cuts, these cuts reduce the exposure of the detector by decreasing the sensitive mass, and uncertainty in position determination may make it impossible to adequately remove such events in certain detectors. In this paper, we provide a new technique for substantially reducing these surface backgrounds in liquid argon (LAr) detectors, independent of position cuts. These detectors typically use a coating of tetraphenyl-butadiene (TPB) on the inner surfaces as a wavelength shifter to convert vacuum ultraviolet (VUV) LAr scintillation light to the visible spectrum. We find that TPB scintillation contains a component with a previously unreported exceptionally long lifetime (~ms). We discovered that this component differs significantly in magnitude between alpha, beta, and VUV excitation, which enables the use of pulse shape discrimination to suppress surface backgrounds by more than a factor of 10 3 with negligible loss of dark matter sensitivity. We also discuss how this technique can be extended beyond just LAr experiments.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2012

Intrinsic frame inverse mass tensor as a function of {beta} and {gamma} in the Bohr Hamiltonian

Analytical expressions are derived for the components of the intrinsic frame inverse mass tensor of the Bohr Hamiltonian. These expressions contain parameters which are determined by the experimental data on the B(E2)'s and the excitation energies of the low-lying collective states. It is shown that the nondiagonal component of the intrinsic frame mass tensor has a small effect on the collective motion. It is shown also that the values of the B{sub {beta}{beta}}, B{sub {gamma}{gamma}} and the rotational mass coefficientB{sub 1} differ in the well-deformed nuclei by factor 3 or more.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2017

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1980

Polarization and position measurements of Type III bursts

The positional and polarization characteristics of Type III bursts in the range 24-220 MHz as measured by the Culgoora radioheliograph, spectrograph and spectropolarimeter are reported. The study includes 997 bursts which are of two classes: fundamental-harmonic (F-H) pairs and 'structureless' bursts with no visible F-H structure, and concentrates on the polarization of the bursts and the variation of polarization from centre to limb. The observed centre-to-limb decrease in polarization approximately follows a cosine law. This decrease is not as predicted by simple theory but is consistent with other observations which imply that open field lines from an active region diverge strongly. The observed o-mode polarization of harmonic radiation implies that the wave vectors of Langmuir waves are always parallel, within about 20 deg, to the magnetic field, while the constancy of H polarization with frequency implies that the ratio of gyromagnetic to plasma frequency, the Alfven speed and the plasma beta are constant with height on the open field lines above an active region. Finally, it is inferred that some factor, in addition to the magnetic field strength, controls the polarization of F radiation.

Suzuki, S.↗
NASA NTRS1983

Chromospheric and coronal emissions from the giants in the Hyades

The visible Ca II K and International Ultraviolet Explorer spectra from the four K0 III stars (theta-1, gamma, delta, and epsilon Tau) in the Hyades, along with a field giant of similar spectral type, beta Gem, have been measured. Among the Hyades giants, the range of the high-temperature emissions can be a factor of 6 or more for C IV and an order of magnitude in the X-ray luminosity measured by Stern et al. (1981). For these presumably coeval cluster giants with similar macroscopic parameters, such as age, mass, effective temperature, gravity, and projected rotational velocity, the observed range in chromospheric and coronal emissions is not easily explained by the dominant factors thought to control these emissions in cool stars. It is possible that the emissions are time variable, on a time scale longer than six months. This would be the first evidence that giants undergo magnetic activity cycles similar to those of dwarf stars.

Baliunas, S. L.↗
DOE OSTI2017

Calculation of the Geometric Factor in a New Experiment Aimed at Studying Radiative Neutron Decay

A new experiment aimed at studying radiative neutron decay is proposed. The respective experimental procedure reduces to measuring the time spectra of triple coincidences of the emitted photon, beta electron, and recoil proton along with the spectrum of double coincidences of ordinary decay products. By means of this procedure, we were able to measure for the first time the branching ratio for radiative neutron decay, BR = (3.2 ± 1.6) × 10{sup −3} (at a confidence level of C.L. = 99.7%, the photon energy being in excess of 35 keV) in 2005 at our old setup. The average value of this branching ratio was greater by a factor of 1.5 than its theoretical counterpart calculated on the basis of the Standard Model. However, we cannot state that we have seen a deviation fromthe StandardModel prediction since the experimental error was quite large in that experiment. The present study is devoted to implementing, by means of the popular Geant4 code package, a computer analog of the respective experiment at a new facility. Our calculations reveal that the resulting geometri©factor values make it possible to a accumulate, in a live experiment, a data sample sufficient for measuring the above branching ratio to a precision of a few percent.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗