Asteroseismology of 16000 Kepler Red Giants: Global Oscillation Parameters, Masses, and Radii

The Kepler mission has provided exquisite data to perform an ensemble asteroseismic analysis on evolved stars. In this work we systematically characterize solar-like oscillations and granulation for 16,094 oscillating red giants, using end-of-mission long-cadence data. We produced a homogeneous catalog of the frequency of maximum power (typical uncertainty $\sigma_{\nu_{\rm max}}$=1.6\%), the mean large frequency separation ($\sigma_{\Delta\nu}$=0.6\%), oscillation amplitude ($\sigma_{\rm A}$=4.7\%), granulation power ($\sigma_{\rm gran}$=8.6\%), power excess width ($\sigma_{\rm width}$=8.8\%), seismically-derived stellar mass ($\sigma_{\rm M}$=7.8\%), radius ($\sigma_{\rm R}$=2.9\%), and thus surface gravity ($\sigma_{\log g}$=0.01 dex). Thanks to the large red giant sample, we confirm that red-giant-branch (RGB) and helium-core-burning (HeB) stars collectively differ in the distribution of oscillation amplitude, granulation power, and width of power excess, which is mainly due to the mass difference. The distribution of oscillation amplitudes shows an extremely sharp upper edge at fixed $\nu_{\rm max}$, which might hold clues to understand the excitation and damping mechanisms of the oscillation modes. We find both oscillation amplitude and granulation power depend on metallicity, causing a spread of 15\% in oscillation amplitudes and a spread of 25\% in granulation power from [Fe/H]=-0.7 to 0.5 dex. Our asteroseismic stellar properties can be used as reliable distance indicators and age proxies for mapping and dating galactic stellar populations observed by Kepler. They will also provide an excellent opportunity to test asteroseismology using Gaia parallaxes, and lift degeneracies in deriving atmospheric parameters in large spectroscopic surveys such as APOGEE and LAMOST.Comment: Accepted for publication in ApJS. Both table 1 and 2 are available for download as ancillary file

Background Parenchymal Enhancement of the Contralateral Normal Breast: Association with Tumor Response in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

AbstractPURPOSE: This study investigated the association between background parenchymal enhancement (BPE) and pathologic response to neoadjuvant chemotherapy (NAC). METHODS: A total of 46 patients diagnosed with invasive breast cancer were analyzed. Each patient had three magnetic resonance imaging (MRI) studies, one pre-treatment and two follow-up (F/U) MRI studies. BPE was measured as the averaged enhancement of the whole fibroglandular tissues. The pre-treatment BPE and the changes in the F/U MRI were compared between patients achieving pathologic complete response (pCR) versus those not. Subgroup analyses based on age, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) status of their cancers were also performed. RESULTS: The pre-treatment BPE was higher in the pCR group than that in the non-pCR group. Compared to baseline, BPE at F/U-1 was significantly decreased in the pCR group but not in the non-pCR group. In subgroup analysis based on age, these results were seen only in the younger group (<55 years old), not in the older group (≥55 years old). Older patients had a significantly lower pre-treatment BPE than younger patients. In analysis based on molecular biomarkers, a significantly decreased BPE at F/U-1 was only found in the ER-negative pCR group but not in the non-pCR, nor in the ER-positive groups. CONCLUSIONS: A higher pre-treatment BPE showing a significant decrease early after starting NAC was related to pCR in pre/peri-menopausal patients

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Confirming chemical clocks: asteroseismic age dissection of the Milky Way disk(s)

Investigations of the origin and evolution of the Milky Way disk have long relied on chemical and kinematic identification of its components to reconstruct our Galactic past. Difficulties in determining precise stellar ages have restricted most studies to small samples, normally confined to the solar neighbourhood. Here we break this impasse with the help of asteroseismic inference and perform a chronology of the evolution of the disk throughout the age of the Galaxy. We chemically dissect the Milky Way disk population using a sample of red giant stars spanning out to 2~kpc in the solar annulus observed by the {\it Kepler} satellite, with the added dimension of asteroseismic ages. Our results reveal a clear difference in age between the low- and high-$\alpha$ populations, which also show distinct velocity dispersions in the $V$ and $W$ components. We find no tight correlation between age and metallicity nor [$\alpha$/Fe] for the high-$\alpha$ disk stars. Our results indicate that this component formed over a period of more than 2~Gyr with a wide range of [M/H] and [$\alpha$/Fe] independent of time. Our findings show that the kinematic properties of young $\alpha$-rich stars are consistent with the rest of the high-$\alpha$ population and different from the low-$\alpha$ stars of similar age, rendering support to their origin being old stars that went through a mass transfer or stellar merger event, making them appear younger, instead of migration of truly young stars formed close to the Galactic bar

T1rho and T2 relaxation times of the normal adult knee meniscus at 3T : analysis of zonal differences

Background: Prior studies describe histological and immunohistochemical differences in collagen and proteoglycan content in different meniscal zones. The aim of this study is to evaluate horizontal and vertical zonal differentiation of T1rho and T2 relaxation times of the entire meniscus from volunteers without symptom and imaging abnormality. Methods: Twenty volunteers age between 19 and 38 who have no knee-related clinical symptoms, and no history of prior knee surgeries were enrolled in this study. Two T1rho mapping (b-FFE T1rho and SPGR T1rho) and T2 mapping images were acquired with a 3.0-T MR scanner. Each meniscus was divided manually into superficial and deep zones for horizontal zonal analysis. The anterior and posterior horns of each meniscus were divided manually into white, red-white and red zones for vertical zonal analysis. Zonal differences of average relaxation times among each zone, and both inter- and intra-observer reproducibility were statistically analyzed. Results: In horizontal zonal analysis, T1rho relaxation times of the superficial zone tended to be higher than those of the deep zone, and this difference was statistically significant in the medial meniscal segments (84.3 ms vs 76.0 ms on b-FFE, p 0.74) or good (0.60–0.74) in all meniscal segments on both horizontal and vertical zonal analysis, except for inter-class correlation coefficients of the lateral meniscus on SPGR. Compared with SPGR T1rho images, b-FFE T1rho images demonstrated more significant zonal differentiation with higher inter- and intra-observer reproducibility. Conclusions: There are zonal differences in T1rho and T2 relaxation times of the normal meniscus

Confirming chemical clocks: asteroseismic age dissection of the Milky Way disc(s)

Investigations of the origin and evolution of the Milky Way disc have long relied on chemical and kinematic identifications of its components to reconstruct our Galactic past. Difficulties in determining precise stellar ages have restricted most studies to small samples, normally confined to the solar neighbourhood. Here, we break this impasse with the help of asteroseismic inference and perform a chronology of the evolution of the disc throughout the age of the Galaxy. We chemically dissect the Milky Way disc population using a sample of red giant stars spanning out to 2 kpc in the solar annulus observed by the Kepler satellite, with the added dimension of asteroseismic ages. Our results reveal a clear difference in age between the low- and high-α populations, which also show distinct velocity dispersions in the V and W components. We find no tight correlation between age and metallicity nor [α/Fe] for the high-α disc stars. Our results indicate that this component formed over a period of more than 2 Gyr with a wide range of [M/H] and [α/Fe] independent of time. Our findings show that the kinematic properties of young α-rich stars are consistent with the rest of the high-α population and different from the low-α stars of similar age, rendering support to their origin being old stars that went through a mass transfer or stellar merger event, making them appear younger, instead of migration of truly young stars formed close to the Galactic bar

Age determination of galaxy merger remnant stars using asteroseismology

The Milky Way was shaped by the mergers with several galaxies in the past. We search for remnant stars that were born in these foreign galaxies and assess their ages in an effort to put upper limits on the merger times and thereby better understand the evolutionary history of our Galaxy. Using 5D-phase space information from Gaia eDR3, radial velocities from Gaia DR2 and chemical information from apogee DR16, we kinematically and chemically select 21 red giant stars belonging to former dwarf galaxies that merged with the Milky Way. With added asteroseismology from Kepler and K2, we determine the ages of the 21 ex situ stars and 49 in situ stars with an average σage/age of ∼31 per cent. We find that all the ex situ stars are consistent with being older than 8 Gyr. While it is not possible to associate all the stars with a specific dwarf galaxy, we classify eight of them as Gaia-Enceladus/Sausage stars, which is one of the most massive mergers in our Galaxy's history. We determine their mean age to be 9.5 ± 1.3 Gyr consistent with a merger time of 8-10 Gyr ago. The rest of the stars are possibly associated with Kraken, Thamnos, Sequoia, or another extragalactic progenitor. The age determination of ex situ stars paves the way to more accurately pinning down when the merger events occurred and hence provide tight constraints useful for simulating how these events unfolded.Funding for the Stellar Astrophysics Centre was provided by The Danish National Research Foundation (grant agreement no. DNRF106). AH acknowledges support from a Spinoza prize from the Netherlands Research Council (NWO). HHK gratefully acknowledges financial support from a Fellowship at the Institute for Advanced Study. AS acknowledges support from the European Research Council Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, G.A. n. 772293, http://www.asterochronometry.eu). JMDK gratefully acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through an Emmy Noether Research Group (grant number KR4801/1-1), as well as from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). CL acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 852839). JY acknowledges partial support from ERC Synergy Grant WHOLE SUN 810218

Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia.

FLT3 is an attractive therapeutic target in acute lymphoblastic leukemia (ALL) but the mechanism for its activation in this cancer is incompletely understood. Profiling global gene expression in large ALL cohorts, we identify over-expression of FLT3 in ZNF384-rearranged ALL, consistently across cases harboring different fusion partners with ZNF384. Mechanistically, we discover an intergenic enhancer element at the FLT3 locus that is exclusively activated in ZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There is also a global enrichment of active enhancers within ZNF384 binding sites across the genome in ZNF384-rearranged ALL cells. Downregulation of ZNF384 blunts FLT3 activation and decreases ALL cell sensitivity to FLT3 inhibitor gilteritinib in vitro. In patient-derived xenograft models of ZNF384-rearranged ALL, gilteritinib exhibits significant anti-leukemia efficacy as a monotherapy in vivo. Collectively, our results provide insights into FLT3 regulation in ALL and point to potential genomics-guided targeted therapy for this patient population

Calcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Rationale: Cardiomyocytes generated from human induced pluripotent stem cells (hiPSCs) are suggested as the most promising candidate to replenish cardiomyocyte loss in regenerative medicine. Little is known about their calcium homeostasis, the key process underlying excitation-contraction coupling. Objective: We investigated the calcium handling properties of hiPSC-derived cardiomyocytes and compared with those from human embryonic stem cells (hESCs). Methods and Results: We differentiated cardiomyocytes from hiPSCs (IMR90 and KS1) and hESCs (H7 and HES3) with established protocols. Beating outgrowths from embryoid bodies were typically observed 2 weeks after induction. Cells in these outgrowths were stained positively for tropomyosin and sarcomeric alpha-actinin. Reverse-transcription polymerase chain reaction studies demonstrated the expressions of cardiac-specific markers in both hiPSC- and hESC-derived cardiomyocytes. Calcium handling properties of 20-day-old hiPSC- and hESC-derived cardiomyocytes were investigated using fluorescence confocal microscopy. Compared with hESC-derived cardiomyocytes, spontaneous calcium transients from both lines of hiPSC-derived cardiomyocytes were of significantly smaller amplitude and with slower maximal upstroke velocity. Better caffeine-induced calcium handling kinetics in hESC-CMs indicates a higher sacroplasmic recticulum calcium store. Furthermore, in contrast with hESC-derived cardiomyocytes, ryanodine did not reduce the amplitudes, maximal upstroke and decay velocity of calcium transients of hiPSC-derived cardiomyocytes. In addition, spatial inhomogeneity in temporal properties of calcium transients across the width of cardiomyocytes was more pronounced in hiPSC-derived cardiomyocytes than their hESC counterpart as revealed line-scan calcium imaging. Expressions of the key calcium-handling proteins including ryanodine recptor-2 (RyR2), sacroplasmic recticulum calcium-ATPase (SERCA), junction (Jun) and triadin (TRDN), were significantly lower in hiPSC than in hESCs. Conclusions: The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation

Highlights • We compared MRI and neuropsychological test data in twins discordant for VCP mutation. • Affected twin revealed rapid cognitive decline in a span of 1 year. • FTD related cognitive features may precede behavioral changes in VCP disease. • Cognitive-behavioral impairment may be missed on routine neurological exam and MMSE. • Need for a dedicated screening measure to recognize the neurological impairment. ARTICLE IN PRESS Please cite this article in press as: Abhilasha Surampalli, Brian T. Gold, Charles Smith, Rudy J. Abstract Inclusion body myopathy, Paget disease of bone and/or frontotemporal dementia is an autosomal dominant disease caused by mutations in the Valosin Containing Protein (VCP) gene. We compared clinical findings including MRI images and neuropsychological assessment data in affected and unaffected twin brothers aged 56 years from a family with the p.R155C VCP gene mutation. The affected twin presented with a 10 year history of progressive proximal muscle weakness, difficulty swallowing, gastroesophageal reflux, fecal incontinence, and peripheral neuropathy. Comprehensive neuropsychological testing revealed rapid cognitive decline in the absence of any behavioral changes in a span of 1 year. This case illustrates that frontotemporal dementia related cognitive impairment may precede behavioral changes in VCP disease as compared with predominance of behavioral impairment reported in previous studies. Our findings suggest that there is a need to establish VCP disease specific tools and normative rates of decline to detect pre-clinical cognitive impairment among affected individuals