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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

The utility of {sup 82}Rb PET for myocardial viability assessment: Comparison with perfusion-metabolism {sup 82}Rb-{sup 18}F-FDG PET

Background: {sup 82}Rb kinetics may distinguish scar from viable but dysfunctional (hibernating) myocardium. We sought to define the relationship between {sup 82}Rb kinetics and myocardial viability compared with conventional {sup 82}Rb and {sup 18}F-fluorodeoxyglucose (FDG) perfusion-metabolism PET imaging. Methods: Consecutive patients (N = 120) referred for evaluation of myocardial viability prior to revascularization and normal volunteers (N = 37) were reviewed. Dynamic {sup 82}Rb 3D PET data were acquired at rest. {sup 18}F-FDG 3D PET data were acquired after metabolic preparation using a standardized hyperinsulinemic-euglycemic clamp. {sup 82}Rb kinetic parameters K{sub 1}, k{sub 2}, and partition coefficient (KP) were estimated by compartmental modeling Results: Segmental {sup 82}Rb k{sub 2} and KP differed significantly between scarred and hibernating segments identified by Rb-FDG perfusion-metabolism (k{sub 2}, 0.42 ± 0.25 vs. 0.22 ± 0.09 min{sup −1}; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). As compared to Rb-FDG analysis, segmental Rb KP had a c-index, sensitivity and specificity of 0.809, 76% and 84%, respectively, for distinguishing hibernating and scarred segments. Segmental k{sub 2} performed similarly, but with lower specificity (75%, P < .001) Conclusions: In this pilot study, {sup 82}Rb kinetic parameters k{sub 2} and KP, which are readily estimated using a compartmental model commonly used for myocardial blood flow, reliably differentiated hibernating myocardium and scar. Further study is necessary to evaluate their clinical utility for predicting benefit after revascularization. [French] French Abstract: Contexte: La cinétique du {sup 82}Rb pourrait être utilisée pour distinguer la fibrose myocardique des zones viables mais dysfonctionnelles (en hibernation). Dans cette étude, nous avons cherché à définir la relation entre la cinétique du {sup 82}Rb et la viabilité myocardique en comparant les images de perfusion et métabolisme myocardique utilisant le {sup 82}Rb et le {sup 18}F-fluorodésoxyglucose (FDG) Méthodes: les données obtenues chez 120 patients consécutifs (N = 120) référés pour évaluation de la viabilité du myocarde avant revascularisation et 37 volontaires considérés normaux (N = 37) ont été étudieés. Les données TEP 3D dynamiques {sup 82}Rb ont été acquises au repos. Les données TEP 3D au {sup 18}F-FDG ont été acquises après préparation métabolique utilisant une pince hyperinsulémique-euglycémique normalisée. Les paramètres k1, k2 et le coefficient de partage (KP) de la cinétique du {sup 82}R bont été évalues par modélisation compartimentale. Résultats: les paramètres k2 et KP de distribution du {sup 82}Rb se sont révélés significativement différent entre les zones tissulaires cicatricielles fibreuses et celles en hibernation identifiées par étude métabolique au FDG (k2, 0,42 ± 0,25 vs. 0,22 ± 0,09 min{sup −1}; P < 0,0001; KP, 1,33 ± 0,62 vs. 2,25 ± 0,98 ml/g; P < 0,0001). Par rapport aux données FDG, le paramètre KP du rubidium a révélé un indice de concordance de 0,809 et une sensibilité et spécificité de 76% et 84%, pour la distinction des segments en hibernation et cicatrisés. Les résultats du paramètre k2 se sont révélés similaires, mais avec une spécificité plus faible calculée à 75% (P < 0,001). Conclusions: Dans cette étude pilote, les paramètres cinétiques k2 et KP de perfusion myocardique au {sup 82}Rb, qui sont facilement estimés à l’aide d’un modèle compartimental couramment utilisé pour flux sanguin myocardique, ont permis de différencier de manière fiable le myocarde cicatricielle des zones myocardiques hibernantes. Une étude plus approfondie est souhaitable pour valider leur utilité clinique en revacularisation. [Spanish] Spanish Abstract: Antecedentes: La cinética con {sup 82}Rb puede distinguir las cicatrices miocárdicas del tejido viable pero disfuncional (hibernante). Buscamos definir la relación entre la cinética del {sup 82}Rb y la viabilidad miocárdica comparada con las imágenes convencionales de PET con {sup 82}Rb y {sup 18}F-flurodeoxyglucosa (FDG). Métodos: se evaluaron a Pacientes Consecutivos (N = 120) referidos para evaluación de viabilidad miocárdica previos a revascularización y voluntarios normales (N = 37). Los datos de PET 3D dinámico con {sup 82}Rb fueron adquiridos en reposo. Los datos de {sup 18}F-FDG 3D PET fueron adquiridos posterior a la preparación metabólica usando un clamp hiperinsulínico-euglucémico. Los patrones cinéticos K1, k2 y el coeficiente de partición (KP) fueron estimados por el modelo compartimental. Resultados: el k2 y KP del {sup 82}Rb permitueron distinguier el tejido cicatricial de los segmentos hibernados identificados por la vía perfusión metabolismo de Rb-FDG (k{sub 2}, 0.42 ± 0.25 vs. 0.22 ± 0.09 min-1; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). En comparación con el análisis de Rb-FDG, el KP segmentario del Rb tuvo un índice-c, sensbilidad y especificidad de 0.809 76 y 84%, respectivamente, para distinguir segmentos hibernantes y cicatriciales. k2 Segmentario tuvo un desempeño similar pero con una menor especificidad (75%, P < .001). Conclusiones: En este estudio piloto, los parámetros cinéticos k2 y KP del {sup 82}Rb, los cuales son estimados usando un modelo compartimental usado comúnmente para flujo sanguíneo miocárdico, diferenciaron el miocardio hibernante del cicatricial. Se necesita estudiar más a fondo para evaluar la utilidad clínica para la predicción del beneficio posterior a la revascularización [Chinese] Chinese Abstract: 背景: 铷-82({sup 82}Rb)药代动力学可能区分梗死与功能受损但存活的心肌(冬眠心肌)。我们将探讨{sup 82}Rb药代动力学与存活心肌的关系,并与常规的{sup 82}Rb和{sup 18}F-氟脱氧葡萄糖(FDG)灌注-代谢PET显像进行比较。 方法: 连续纳入120名血运重建前评估存活心肌的患者和37名正常志愿者。获得静息{sup 82}Rb 3D-PET动态采集数据;采用标准化的高胰岛素 - 正葡萄糖钳夹试验得到{sup 18}F-FDG 3D PET代谢显像数据; 通过房室模型计算{sup 82}Rb动力学参数k{sub 1},k{sub 2}和分配系数(KP)。 结果: 以Rb-FDG灌注代谢显像鉴定疤痕心肌组和冬眠心肌组,两组的{sup 82}Rb节段性 k{sub 2}值和KP值有明显差异(k{sub 2}, 0.42 ± 0.25 vs 0.22 ± 0.09 min{sup −1}; P < .0001; KP, 1.33 ± 0.62 vs 2.25 ± 0.98 ml/g; P < .0001)。以Rb-FDG灌注代谢显像为诊断标准,{sup 82}Rb节段性 KP对疤痕和冬眠心肌鉴别效能的c指数,敏感性和特异性分别是0.809, 76%和84%。节段性k{sub 2}的鉴别效能与KP相似,但特异性较低(75%,P < .001)。 结论: 在本试验性研究中,通过常规用于{sup 82}Rb心肌血流量测定的房室模型计算出的{sup 82}Rb动力学参数k{sub 2}和KP,可以有效的区分冬眠心肌和瘢痕心肌。 但需要进一步的研究来评估其对预测血运重建是否获益的临床价值。.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Zodiacal exoplanets in time (Zeit). I. A Neptune-sized planet orbiting an M4.5 dwarf in the Hyades star cluster

Studying the properties of young planetary systems can shed light on how the dynamics and structure of planets evolve during their most formative years. Recent K2 observations of nearby young clusters (10–800 Myr) have facilitated the discovery of such planetary systems. Here we report the discovery of a Neptune-sized planet transiting an M4.5 dwarf (K2-25) in the Hyades cluster (650–800 Myr). The light curve shows a strong periodic signal at 1.88 days, which we attribute to spot coverage and rotation. We confirm that the planet host is a member of the Hyades by measuring the radial velocity of the system with the high-resolution near-infrared spectrograph Immersion Grating Infrared Spectrometer. This enables us to calculate a distance based on K2-25's kinematics and membership to the Hyades, which in turn provides a stellar radius and mass to ≃5%–10%, better than what is currently possible for most Kepler M dwarfs (12%–20%). We use the derived stellar density as a prior on fitting the K2 transit photometry, which provides weak constraints on eccentricity. Utilizing a combination of adaptive optics imaging and high-resolution spectra, we rule out the possibility that the signal is due to a bound or background eclipsing binary, confirming the transits’ planetary origin. K2-25b has a radius (3.43{sub −0.31}{sup +0.95} R{sub ⊕}) much larger than older Kepler planets with similar orbital periods (3.485 days) and host-star masses (0.29 M{sub ⊙}). This suggests that close-in planets lose some of their atmospheres past the first few hundred million years. Additional transiting planets around the Hyades, Pleiades, and Praesepe clusters from K2 will help confirm whether this planet is atypical or representative of other close-in planets of similar age.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2016

The spin relaxation of nitrogen donors in 6H SiC crystals as studied by the electron spin echo method

We present the detailed study of the spin kinetics of the nitrogen (N) donor electrons in 6H SiC wafers grown by the Lely method and by the sublimation “sandwich method” (SSM) with a donor concentration of about 10{sup 17 }cm{sup −3} at T = 10–40 K. The donor electrons of the N donors substituting quasi-cubic “k1” and “k2” sites (N{sub k1,k2}) in both types of the samples revealed the similar temperature dependence of the spin-lattice relaxation rate (T{sub 1}{sup −1}), which was described by the direct one-phonon and two-phonon processes induced by the acoustic phonons proportional to T and to T{sup 9}, respectively. The character of the temperature dependence of the T{sub 1}{sup −1} for the donor electrons of N substituting hexagonal (“h”) site (N{sub h}) in both types of 6H SiC samples indicates that the donor electrons relax through the fast-relaxing centers by means of the cross-relaxation process. The observed enhancement of the phase memory relaxation rate (T{sub m}{sup −1}) with the temperature increase for the N{sub h} donors in both types of the samples, as well as for the N{sub k1,k2} donors in Lely grown 6H SiC, was explained by the growth of the free electron concentration with the temperature increase and their exchange scattering at the N donor centers. The observed significant shortening of the phase memory relaxation time T{sub m} for the N{sub k1,k2} donors in the SSM grown sample with the temperature lowering is caused by hopping motion of the electrons between the occupied and unoccupied states of the N donors at N{sub h} and N{sub k1,k2} sites. The impact of the N donor pairs, triads, distant donor pairs formed in n-type 6H SiC wafers on the spin relaxation times was discussed.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2013

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2 products. • JWH-018, JWH-073 and their human metabolites have high affinity for CB{sub 2} receptors. • JWH-018, JWH-073 and their human metabolites are potent agonists at CB{sub 2} receptors. • JWH-018, JWH-073 and their metabolites exhibit distinct CB{sub 2} signaling properties. • Studies of JWH-018 and JWH-073 should consider actions at CB{sub 1} and CB{sub 2} receptors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Sgr B2(N): A bipolar outflow and rotating hot core revealed by ALMA

We present the results of SiO (2 − 1) and SO{sub 2} (12{sub 4,8}--13{sub 3,11}) line observations of Sgr B2(N) made with the Atacama Large Millimeter/submillimeter Array at an angular resolution of ∼2″. Our analysis of the SiO and SO{sub 2} line emission reveals a bipolar molecular outflow in an east–west direction whose driving source is located at K2. In addition, the SO{sub 2} line core shows a north–south velocity gradient most probably indicating a hot core of molecular gas rotating around K2. Fractional abundances of SO{sub 2} and SiO (X(SO{sub 2}) and X(SiO), respectively) in the outflowing molecular gas are derived from comparisons with the C{sup 18}O emission. Assuming an excitation temperature of 100 ± 50 K, we calculate X(SO{sub 2}) = 2.3{sub −0.4}{sup +2.6} × 10{sup −8} and X(SiO) = 1.2{sub −0.1}{sup +0.1} × 10{sup −9}. The outflow from Sgr B2(N) K2 is characterized as a young (5 × 10{sup 3} yr) and massive (∼2000 M{sub ⊙}) but moderately collimated (∼60°) outflow. We also report a possible detection of the SiO (v=2,J=2--1) maser emission from the position of K2. If confirmed, it would make Sgr B2(N) the fourth star-forming region associated with SiO masers.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

Hydrokinetic Energy Conversion by Flow-Induced Oscillation of Two Tandem Cylinders of Different Stiffness

Abstract The vortex-induced vibration for aquatic clean energy (VIVACE) converter harnesses hydrokinetic energy by enhancing flow-induced oscillations (FIOs) of elastically supported rigid cylinders in a river, tide, or ocean current. The harnessing power depends on the intensity of the oscillation, which is a consequence of the flow–structure interaction. The inflow condition for the downstream (second) cylinder is slowed down and perturbed by the upstream (first) cylinder, due to the shielding effect. Therefore, the optimal structural parameters, i.e., stiffness and damping ratio, for the second cylinder may be different from the first cylinder, in terms of energy harnessing. To improve the performance of the VIVACE converter, a series of experiments are conducted in a recirculating water channel, with various stiffness combinations of two cylinders in tandem. Results show that the stiffness of the second cylinder, K2, does not affect the energy harnessing power in vortex-induced vibration (VIV) occurring at low speeds, because the oscillation of the downstream cylinder in this velocity range is completely dominated by the wake of the upstream cylinder. K2 has a great influence on the harnessing power at higher velocities in the transition region from VIV to galloping and in galloping. Changing K2 onsets and enhances galloping at lower flow velocity and harnesses up to 110% more energy than the case of K1 = K2.

Engineering↗
DOE OSTI2025

Microbial vitamin biosynthesis links gut microbiota dynamics to chemotherapy toxicity

ABSTRACT Dose-limiting toxicities pose a major barrier to cancer treatment. While preclinical studies show that the gut microbiota influences and is influenced by anticancer drugs, data from patients paired with careful side effect monitoring remains limited. Here, we investigate capecitabine (CAP)-microbiome interactions through longitudinal metagenomic sequencing of stool from 56 advanced colorectal cancer patients. CAP significantly altered the gut microbiome, enriching for menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, targeted gene deletions, and media supplementation revealed that menaquinol biosynthesis protectsEscherichia colifrom drug toxicity. Stool menaquinol gene and metabolite levels were associated with decreased peripheral sensory neuropathy. Machine learning models trained in this cohort predicted toxicities in an independent cohort. Taken together, these results suggest treatment-associated increases in microbial vitamin biosynthesis serve a chemoprotective role for bacterial and host cells. Further, our findings provide a foundation for in-depth mechanistic dissection, human intervention studies, and extension to other cancer treatments. IMPORTANCE Side effects are common during the treatment of cancer. The trillions of microbes found within the human gut are sensitive to anticancer drugs, but the effects of treatment-induced shifts in gut microbes for side effects remain poorly understood. We profiled gut microbes in colorectal cancer patients treated with capecitabine and carefully monitored side effects. We observed a marked expansion in genes for producing vitamin K2 (menaquinone). Vitamin K2 rescued gut bacterial growth and was associated with decreased side effects in patients. We then used information about gut microbes to develop a predictive model of drug toxicity that was validated in an independent cohort. These results suggest that treatment-associated increases in bacterial vitamin production protect both bacteria and host cells from drug toxicity, providing new opportunities for intervention and motivating the need to better understand how dietary intake and bacterial production of micronutrients like vitamin K2 influence cancer treatment outcomes.

Microbiology↗
DOE OSTI2016

ZODIACAL EXOPLANETS IN TIME (ZEIT). III. A SHORT-PERIOD PLANET ORBITING A PRE-MAIN-SEQUENCE STAR IN THE UPPER SCORPIUS OB ASSOCIATION

We confirm and characterize a close-in (P{sub orb} = 5.425 days), super-Neptune sized (5.04{sub −0.37}{sup +0.34} R{sub ⊕}) planet transiting K2-33 (2MASS J16101473-1919095), a late-type (M3) pre-main-sequence (11 Myr old) star in the Upper Scorpius subgroup of the Scorpius–Centaurus OB association. The host star has the kinematics of a member of the Upper Scorpius OB association, and its spectrum contains lithium absorption, an unambiguous sign of youth (<20 Myr) in late-type dwarfs. We combine photometry from K2 and the ground-based MEarth project to refine the planet’s properties and constrain the host star’s density. We determine K2-33’s bolometric flux and effective temperature from moderate-resolution spectra. By utilizing isochrones that include the effects of magnetic fields, we derive a precise radius (6%–7%) and mass (16%) for the host star, and a stellar age consistent with the established value for Upper Scorpius. Follow-up high-resolution imaging and Doppler spectroscopy confirm that the transiting object is not a stellar companion or a background eclipsing binary blended with the target. The shape of the transit, the constancy of the transit depth and periodicity over 1.5 yr, and the independence with wavelength rule out stellar variability or a dust cloud or debris disk partially occulting the star as the source of the signal; we conclude that it must instead be planetary in origin. The existence of K2-33b suggests that close-in planets can form in situ or migrate within ∼10 Myr, e.g., via interactions with a disk, and that long-timescale dynamical migration such as by Lidov–Kozai or planet–planet scattering is not responsible for all short-period planets.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

Wavelength Dependence of Activity-induced Photometric Variations for Young Cool Stars in Hyades

We investigate photometric variations due to stellar activity that induce systematic radial-velocity errors (so-called “jitter”) for the four targets in the Hyades open cluster observed by the K2 mission (EPIC 210721261, EPIC 210923016, EPIC 247122957, and EPIC 247783757). Applying Gaussian process regressions to the K2 light curves and the near-infrared (NIR) light curves observed with the IRSF 1.4 m telescope, we derive the wavelength dependences of the photometric signals due to stellar activity. To estimate the temporal variations in the photometric variability amplitudes between the two observation periods of K2 and IRSF, separated by more than 2 yr, we analyze a number of K2 targets in Hyades that have also been observed in Campaigns 4 and 13 and find a representative variation rate over 2 yr of 38% ± 71%. Taking this temporal variation into account, we constrain projected sizes and temperature contrast properties of the starspots in the stellar photosphere to be approximately 10% and 0.95%, respectively. These starspot properties can induce relatively large differences in the variability amplitude over different observational passbands, and we find that radial-velocity jitter may be more suppressed in the NIR than previously expected. Our result supports profits of ongoing exoplanet search projects that are attempting to detect or confirm young planets in open clusters via radial-velocity measurements in the NIR.

47 OTHER INSTRUMENTATION↗
NASA NTRS1972

High resolution spectroscopy of the disk chromosphere. II - Time sequence observations of Ca II H and K emissions.

Two independent sets of high resolution time series spectra of the Ca II H and K emission obtained at the Solar Tower and at the Big Dome of the Sacramento Peak Observatory on September 11th, 1971 are reported. The evolutionary behavior of the emission first reported by Wilson and Evans is confirmed, but the detail of the evolution is found to be more complex. In one case, a doubly peaked feature showing some K3 emission evolves into a single K2 (red) peak with no K3 emission. Coincidentally, a neighboring doubly peaked feature evolves to a very strong blue peak. In an entirely independent sequence a doubly peaked feature evolves into a single red peak. The K2 emission then fades completely although the continuum threads are still strong. Finally a strong K2 blue peak appears. It is concluded that the observed evolution of the K2 emission is due to temporal variations in the physical conditions which give rise to them.

Wilson, P. R.↗