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At least 127 records · Page 7

Studying the Effects of Overlapping Objects in Dark Energy

Observing the clustering of galaxies allows us to calculate cosmological parameters necessary for understanding dark energy. However, as the density of observed objects increases, the probability of these objects blending likewise increases, causing multiplegalaxies to be observed as one. This affects the calculated values of parameters such as the galaxy bias (b) and the matter energy density (ΩM). To see whether the bias from incorrectly inferring the galaxy count is significant, we compare the correlation functions in simulated data for “observed” and “true” data sets with one-to-one andmultiple-to-one correspondences.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer’s disease

The molecular mechanisms underlying neuronal dysfunction in Alzheimer’s disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant’s real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau’s synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

60 APPLIED LIFE SCIENCES↗

Structural Similarities and Overlapping Activities among Dihydroflavonol 4-Reductase, Flavanone 4-Reductase, and Anthocyanidin Reductase Offer Metabolic Flexibility in the Flavonoid Pathway

Flavonoids are potent antioxidants that play a role in defense against pathogens, UV-radiation, and the detoxification of reactive oxygen species. Dihydroflavonol 4-reductase (DFR) and flavanone 4-reductase (FNR) reduce dihydroflavonols and flavanones, respectively, using NAD(P)H to produce flavan-(3)-4-(di)ols in flavonoid biosynthesis. Anthocyanidin reductase (ANR) reduces anthocyanidins to flavan-3-ols. In addition to their sequences, the 3D structures of recombinant DFR, FNR and ANR from sorghum and switchgrass showed a high level of similarity. The catalytic mechanism, substrate-specificity and key residues of three reductases were deduced from crystal structures, site-directed mutagenesis, molecular docking, kinetics, and thermodynamic ana-lyses. Although DFR displayed its highest activity against dihydroflavonols, it also showed activity against flavanones and anthocyanidins. It was inhibited by the flavonol quercetin and high concentrations of dihydroflavonols/flavonones. SbFNR1 and SbFNR2 did not show any activity against dihydroflavonols. However, SbFNR1 displayed activity against flavanones and ANR activity against two anthocyanidins, cyanidin and pelargonidin. Therefore, SbFNR1 and SbFNR2 could be specific ANR isozymes without delphinidin activity. Sorghum has high concentrations of 3-deoxyanthocyanidins in vivo, supporting the observed high activity of SbDFR against flavonols. Mining of expression data indicated substantial induction of these three reductase genes in both switchgrass and sorghum in response to biotic stress. Key signature sequences for proper DFR/ANR classification are proposed and could form the basis for future metabolic engineering of flavonoid metabolism.

3-deoxyanthocyanidin↗

NGC 4869 in the Coma Cluster: Twist, Wrap, Overlap, and Bend

The upgraded Giant Metrewave Radio Telescope (GMRT) has been used to image the head–tail radio galaxy NGC 4869 in the Coma cluster with an angular resolution of 6.″26 at 250–500 MHz and 2.″18 at the 1050–1450 MHz bands. The archival legacy GMRT data have also been used to image the source with angular resolutions from 4.″9 to 21.″8 at 610 MHz, 325 MHz, 240 MHz, and 150 MHz. We find that the ∼200 kpc scale radio morphology consists of five distinct regions with the clear presence of a pinch at ≈1.′4 (=38.8 kpc) and a ridge at ≈3.′4 (=94.2 kpc) from the head. The sharp bend by ∼70° at ∼3.′5 (=97 kpc) from the head is possibly due to projection effects. The radio spectra show progressive spectral steepening as a function of distance from the head and there is possibly re-acceleration of the synchrotron electrons and perhaps also magnetic field regeneration in the 6″–208″ (=2.8–96.1 kpc) region of the jet. We report a steep spectrum sheath layer enveloping a flat spectrum spine, hinting at a transverse velocity structure with a fast-moving spine surrounded by a slow-moving sheath layer. We also derive the lifetimes of the radiating electrons and equipartition parameters. A plausible explanation for the characteristic feature, a ridge of emission perpendicular to the direction of tail is the flaring of a straight, collimated radio jet as it crosses a surface brightness edge due to Kelvin–Helmholtz instabilities.

79 ASTRONOMY AND ASTROPHYSICS↗

K2-79b and K2-222b: Mass Measurements of Two Small Exoplanets with Periods beyond 10 days that Overlap with Periodic Magnetic Activity Signals

We present mass and radius measurements of K2-79b and K2-222b, two transiting exoplanets orbiting active G-type stars observed with HARPS-N and K2. Their respective 10.99 day and 15.39 day orbital periods fall near periods of signals induced by stellar magnetic activity. The two signals might therefore interfere and lead to an inaccurate estimate of exoplanet mass. We present a method to mitigate these effects when radial velocity (RV) and activityindicator observations are available over multiple observing seasons and the orbital period of the exoplanet is known. We perform correlation and periodogram analyses on subsets composed of each target's two observing seasons, in addition to the full data sets. For both targets, these analyses reveal an optimal season with little to no interference at the orbital period of the known exoplanet. We make a confident mass detection of each exoplanet by confirming agreement between fits to the full RV set and the optimal season. For K2-79b, we measure a mass of 11.8 ± 3.6 M ⊕ and a radius of 4.09 ± 0.17 R ⊕ . For K2-222b, we measure a mass of 8.0 ± 1.8 M ⊕ and a radius of 2.35 ± 0.08 R ⊕ . According to model predictions, K2-79b is a highly irradiated Uranus analog and K2-222b hosts significant amounts of water ice. We also present a RV solution for a candidate second companion orbiting K2-222 at 147.5 days.

79 ASTRONOMY AND ASTROPHYSICS↗

Studying the effects of overlapping objects in dark energy

Observing the clustering of galaxies allows us to calculate cosmological parameters necessary for understanding dark energy. However, as the density of observed objects increases, the probability of these objects blending likewise increases, causing multiple galaxies to be observed as one. This affects the inferred values of parameters such as the galaxy bias (b) and the matter energy density (ΩM). To see whether the bias from incorrectly inferring the galaxy count is significant, we compare the correlation functions in simulated data for “true” and “observed” data sets with one-to-one and multiple-to-one correspondences, respectively. For each data set, we create two correlation functions: one “measured” function directly relying on the galaxies’ positions using the TreeCorr python library, and one “model” derived mathematically from the galaxies’ power spectrum using the Cosmological Core Library (CCL). By minimizing the residual between these two functions, we compute the ideal values for b and ΩM across the various possible redshifts that position the galaxies in three dimensional space. This minimization is done with an Markov chain Monte Carlo (MCMC) estimate that finds one value of ΩM and ten values for b corresponding to the ten redshift bins ranging from z = 0.2 to z = 1.2. We find that neither b nor ΩM is particularly affected by inclusion of blended galaxies. Though there is room for improvement, the data suggests that the fluctuations we found are a result of noise or limitations on the modeling rather than blending explicitly.

79 ASTRONOMY AND ASTROPHYSICS↗