Abstract
We present a new and independent determination of the local value of the Hubble constant based on a calibration of the tip of the red giant branch (TRGB) applied to Type Ia supernovae ...(SNe Ia). We find a value of
H
0
= 69.8 ± 0.8 (±1.1% stat) ± 1.7 (±2.4% sys) km s
−1
Mpc
−1
. The TRGB method is both precise and accurate and is parallel to but independent of the Cepheid distance scale. Our value sits midway in the range defined by the current Hubble tension. It agrees at the 1.2
σ
level with that of the Planck Collaboration et al. estimate and at the 1.7
σ
level with the
Hubble Space Telescope
(
HST
)
SHoES
measurement of
H
0
based on the Cepheid distance scale. The TRGB distances have been measured using deep
HST
Advanced Camera for Surveys imaging of galaxy halos. The zero-point of the TRGB calibration is set with a distance modulus to the Large Magellanic Cloud of 18.477 ± 0.004 (stat) ± 0.020 (sys) mag, based on measurement of 20 late-type detached eclipsing binary stars, combined with an
HST
parallax calibration of a 3.6
μ
m Cepheid Leavitt law based on
Spitzer
observations. We anchor the TRGB distances to galaxies that extend our measurement into the Hubble flow using the recently completed Carnegie Supernova Project I ( CSP-I ) sample containing about 100 well-observed SNe Ia . There are several advantages of halo TRGB distance measurements relative to Cepheid variables; these include low halo reddening, minimal effects of crowding or blending of the photometry, only a shallow (calibrated) sensitivity to metallicity in the
I
band, and no need for multiple epochs of observations or concerns of different slopes with period. In addition, the host masses of our TRGB host-galaxy sample are higher, on average, than those of the Cepheid sample, better matching the range of host-galaxy masses in the CSP-I distant sample and reducing potential systematic effects in the SNe Ia measurements.
We present an analysis of the final data release of the Carnegie Supernova Project I, focusing on the absolute calibration of the luminosity-decline rate relation for Type Ia supernovae (SNe Ia) ...using new intrinsic color relations with respect to the color-stretch parameter, sBV, enabling improved dust extinction corrections. We investigate to what degree the so-called fast-declining SNe Ia can be used to determine accurate extragalactic distances. We estimate the intrinsic scatter in the luminosity-decline rate relation and find it ranges from 0.13 mag to 0.18 mag with no obvious dependence on wavelength. Using the Cepheid variable star data from the SH0ES project, the SN Ia distance scale is calibrated and the Hubble constant is estimated using our optical and near-infrared sample, and these results are compared to those determined exclusively from a near-infrared subsample. The systematic effect of the supernova's host galaxy mass is investigated as a function of wavelength and is found to decrease toward redder wavelengths, suggesting this effect may be due to dust properties of the host. Using estimates of the dust extinction derived from optical and near-infrared wavelengths and applying these to the H band, we derive a Hubble constant , whereas using a simple B − V color correction applied to the B band yields . Photometry of two calibrating SNe Ia from the CSP-II sample, SN 2012ht and SN 2015F, is presented and used to improve the calibration of the SN Ia distance ladder.
Microparticles (MPs) are small (0.1-1.0 µm) vesicles shed from the surface of cells in response to stress. Whether podocytes produce MPs and whether this production reflects glomerular injury are ...unclear. We examined MP formation in cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-β. Urinary podocyte MPs were assessed in three mouse models of diabetic nephropathy: streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG increased MP release as assessed by flow cytometry (P<0.01 and P<0.05, respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited increased urinary podocyte MPs compared with age-matched nondiabetic mice. Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs compared with wild-type littermates (P<0.01). In 1 week post-STZ-treated and 6- and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our results indicate that podocytes produce MPs that are released into urine. Podocyte-derived MPs are generated by exposure to mechanical stretch and high glucose in vitro and could represent early markers of glomerular injury in diabetic nephropathy.
Noise-induced hearing loss (NIHL) results from a complex interplay of damage to the sensory cells of the inner ear, dysfunction of its lateral wall, axonal retraction of type 1C spiral ganglion ...neurons, and activation of the immune response. We use RiboTag and single-cell RNA sequencing to survey the cell-type-specific molecular landscape of the mouse inner ear before and after noise trauma. We identify induction of the transcription factors STAT3 and IRF7 and immune-related genes across all cell-types. Yet, cell-type-specific transcriptomic changes dominate the response. The ATF3/ATF4 stress-response pathway is robustly induced in the type 1A noise-resilient neurons, potassium transport genes are downregulated in the lateral wall, mRNA metabolism genes are downregulated in outer hair cells, and deafness-associated genes are downregulated in most cell types. This transcriptomic resource is available via the Gene Expression Analysis Resource (gEAR; https://umgear.org/NIHL) and provides a blueprint for the rational development of drugs to prevent and treat NIHL.
Display omitted
•A cell-type-specific transcriptomic map of the cochlear response to noise•Noise-resilient type 1A auditory neurons upregulate the ATF3/4 pathway•Monocytes significantly alter their gene expression in response to noise exposure•STAT3/IRF7 are probable regulators of a general cochlear transcriptomic response to noise
Milon et al. show that cell-type-specific transcriptomic changes following noise exposure dominate the response compared to common changes. The noise-resilient type 1A neurons induce the ATF3/ATF4 stress-response pathway, and the outer hair cells and lateral wall downregulate mRNA metabolism genes and potassium transport genes, respectively.
Human genetic diversity in southern Europe is higher than in other regions of the continent. This difference has been attributed to postglacial expansions, the demic diffusion of agriculture from the ...Near East, and gene flow from Africa. Using SNP data from 2,099 individuals in 43 populations, we show that estimates of recent shared ancestry between Europe and Africa are substantially increased when gene flow from North Africans, rather than Sub-Saharan Africans, is considered. The gradient of North African ancestry accounts for previous observations of low levels of sharing with Sub-Saharan Africa and is independent of recent gene flow from the Near East. The source of genetic diversity in southern Europe has important biomedical implications; we find that most disease risk alleles from genome-wide association studies follow expected patterns of divergence between Europe and North Africa, with the principal exception of multiple sclerosis.
We present an updated analysis of the intrinsic colors of Type Ia supernova (SNe Ia) using the latest data release of the Carnegie Supernova Project. We introduce a new light-curve parameter very ...similar to stretch that is better suited for fast-declining events, and find that these peculiar types can be seen as extensions to the population of "normal" SNe Ia. With a larger number of objects, an updated fit to the Lira relation is presented along with evidence for a dependence on the late-time slope of the B - V light-curves with stretch and color. Using the full wavelength range from u to H band, we place constraints on the reddening law for the sample as a whole and also for individual events/hosts based solely on the observed colors. The photometric data continue to favor low values of R sub(V), though with large variations from event to event, indicating an intrinsic distribution. We confirm the findings of other groups that there appears to be a correlation between the derived reddening law, R sub(V), and the color excess, E(B - V), such that larger E(B - V) tends to favor lower R sub(V). The intrinsic u-band colors show a relatively large scatter that cannot be explained by variations in R sub(V) or by the Goobar power-law for circumstellar dust, but rather is correlated with spectroscopic features of the supernova and is therefore likely due to metallicity effects.
Interest in sigma-1 receptors (S1Rs) has significantly increased in the last 25 years and more recently for their role in pain modulation. S1Rs are novel chaperone proteins that modulate several ...cellular processes and can modulate the activity of many ion channels and receptors. They are heavily localized in pain pathways, leading to the development of S1R antagonists for pain modulation. Although the exact mechanism by which S1R antagonists act is unclear, there has been marked advances in the preclinical and clinical development of S1R antagonists.
This review covers the brief history of S1Rs and the research leading to the development of S1R antagonists in clinical trials for chronic pain. Focus is given to E-52862 and
18
FFTC-146 (aka CM-304) as their clinical development has broken ground for S1R antagonists- with both being first-in-class ligands for treatment and diagnostic imaging, respectively.
S1R antagonists represent a unique intracellular target for pain modulation, due to the receptor's chaperone activity in modulating various proteins in pain pathways. The research on S1R has grown exponentially in the last 20 years, and as more is understood about the basic science of the receptor, the drug development in this field will also flourish.
Canopy structure from space using GEDI lidar Hakkenberg, Christopher R; Tang, Hao; Burns, Patrick ...
Frontiers in ecology and the environment,
February 2023, 2023-02-00, 20230201, Letnik:
21, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Hakkenberg et al discuss the Global Ecosystem Dynamics Investigation (GEDI) lidar mission, the first spaceborne lidar investigation specifically designed to measure canopy structure for ecosystem ...science. Although GEDI's near-global coverage and temporal repeat frequency have the potential to transform global forest monitoring capabilities, some important considerations should be noted for ecologists hoping to employ these novel datasets. At present, GEDI does not by itself provide spatially continuous maps of canopy structure at moderately fine spatial resolutions. To mitigate against GEDI's discontinuous sampling scheme and provide analysis-ready data for the research community, the GEDI science team has released a series of gridded data products of structural features like canopy height and aboveground biomass.
Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical ...next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping).
PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial.
Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19-9 (CA-19-9), and favorable RECIST imaging response.
PDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC. See related commentary by Zhang et al., p. 3176.
The Fukushima-Daiichi nuclear accident brought together compromised irradiated fuel and large amounts of seawater in a high radiation field. Based on newly acquired thermochemical data for a series ...of uranyl peroxide compounds containing charge-balancing alkali cations, here we show that nanoscale cage clusters containing as many as 60 uranyl ions, bonded through peroxide and hydroxide bridges, are likely to form in solution or as precipitates under such conditions. These species will enhance the corrosion of the damaged fuel and, being thermodynamically stable and kinetically persistent in the absence of peroxide, they can potentially transport uranium over long distances.
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