Cells from the same individual share common genetic and environmental backgrounds and are not statistically independent; therefore, they are subsamples or pseudoreplicates. Thus, single-cell data ...have a hierarchical structure that many current single-cell methods do not address, leading to biased inference, highly inflated type 1 error rates, and reduced robustness and reproducibility. This includes methods that use a batch effect correction for individual as a means of accounting for within-sample correlation. Here, we document this dependence across a range of cell types and show that pseudo-bulk aggregation methods are conservative and underpowered relative to mixed models. To compute differential expression within a specific cell type across treatment groups, we propose applying generalized linear mixed models with a random effect for individual, to properly account for both zero inflation and the correlation structure among measures from cells within an individual. Finally, we provide power estimates across a range of experimental conditions to assist researchers in designing appropriately powered studies.
Abstract
Solar wind charge exchange (SWCX) is the primary contamination of soft X-ray emission lines from the Milky Way (MW) hot gas. We report a solar cycle (≈10 yr) temporal variation of observed O
...vii
and O
viii
emission line measurements in the XMM-Newton archive, which is tightly correlated with the solar cycle traced by the sunspot number (SSN). This temporal variation is expected to be associated with the heliospheric SWCX. Another observed correlation is that higher solar wind (SW) fluxes lead to higher O
vii
or O
viii
fluxes, which is due to the magnetospheric SWCX. We construct an empirical model to reproduce the observed correlation between the line measurements and the solar activity (i.e., the SW flux and the SSN). With this model we discovered a lag of
0.91
−
0.22
+
0.20
yr between the O
vii
flux and the SSN. This time lag is a combination of the SW transit time within the heliosphere, the lag of the neutral gas distribution responding to solar activity, and the intrinsic lag between the SSN and the launch of a high-energy SW (i.e., O
7+
and O
8+
). MW O
vii
and O
viii
fluxes have mean values of 5.4 L.U. and 1.7 L.U., which are reduced by 50% and 30%, compared to studies where the SWCX contamination is not removed. This correction also changes the determination of the density distribution and the temperature profile of the MW hot gas.
Study design is a critical aspect of any experiment, and sample size calculations for statistical power that are consistent with that study design are central to robust and reproducible results. ...However, the existing power calculators for tests of differential expression in single-cell RNA-seq data focus on the total number of cells and not the number of independent experimental units, the true unit of interest for power. Thus, current methods grossly overestimate the power.
Hierarchicell is the first single-cell power calculator to explicitly simulate and account for the hierarchical correlation structure (i.e., within sample correlation) that exists in single-cell RNA-seq data. Hierarchicell, an R-package available on GitHub, estimates the within sample correlation structure from real data to simulate hierarchical single-cell RNA-seq data and estimate power for tests of differential expression. This multi-stage approach models gene dropout rates, intra-individual dispersion, inter-individual variation, variable or fixed number of cells per individual, and the correlation among cells within an individual. Without modeling the within sample correlation structure and without properly accounting for the correlation in downstream analysis, we demonstrate that estimates of power are falsely inflated. Hierarchicell can be used to estimate power for binary and continuous phenotypes based on user-specified number of independent experimental units (e.g., individuals) and cells within the experimental unit.
Hierarchicell is a user-friendly R-package that provides accurate estimates of power for testing hypotheses of differential expression in single-cell RNA-seq data. This R-package represents an important addition to single-cell RNA analytic tools and will help researchers design experiments with appropriate and accurate power, increasing discovery and improving robustness and reproducibility.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SYNOPSIS We investigate the implementation of Robotic Process Automation (RPA) software in public accounting by interviewing RPA leaders at Big 4 firms. RPA software automates the input, processing, ...and output of data to streamline repetitive, mundane tasks. Many of our findings are unique to accounting. For instance, participants report tax services are furthest along in RPA adoption, followed by advisory and assurance services. Furthermore, RPA has not impacted fees, but there is concern that clients may desire fee reductions due to decreased employee hours. Finally, unlike other technology implementations, RPA adoption is driven primarily by lower-level employees. Similar to other domains, our results indicate massive efficiency and effectiveness gains from RPA implementation. Also, interviewees do not expect reduced head count to result from RPA use. This study is the first to discuss the benefits, opportunities, and challenges to implementing RPA in accounting and serves as a catalyst for future research.
We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of ...heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30–40 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.
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•Critical feedback increases the likelihood of entrepreneurial pivoting.•Self-leadership moderates the relationship between critical feedback and pivoting.•Self-leadership is a ...resource that aids in reacting to critical feedback.
This paper draws on the self-leadership literature to explore who is more likely to respond to critical performance feedback in an early-stage entrepreneurial context. We perform a multi-round laboratory experiment in which participants brainstorm ideas for cricket-based food products, select their best idea, receive randomly generated feedback indicating that their idea is either above average (i.e., non-critical feedback) or below average (i.e., critical feedback), and then decide whether to stick with their original or pivot to a different idea. Results reveal that individuals low in behavioral awareness and constructive cognition, and those high in task motivation, are more likely to pivot to a new product in response to critical feedback. Given the central role responding to feedback plays in entrepreneurship (and in other contexts), these results shed needed light on the question of who is more likely to adapt in response to critical feedback and who is predisposed toward inaction.
Ants exhibit a striking diversity of reproductive systems, varying in traits such as the number of reproductives per colony 1, the mode of daughter production (sexual or asexual) 2, and the mode of ...caste determination (genetic or environmental) 3. Species employing mixed reproductive systems present a unique opportunity to explore the causes and consequences of alternative breeding strategies. Mixed reproductive systems in ants include social polymorphism in colony queen number, whereby single-queen (monogyne) and multiple-queen (polygyne) colonies co-occur within species 4–7, and facultative asexuality, in which female offspring may be produced sexually or asexually within colonies 8–13. Here, we document a remarkable confluence of multiple mixed reproductive systems in the tropical fire ant, Solenopsis geminata, in a population with three important features: (1) polygyne colonies produce workers sexually but queens asexually, whereas monogyne colonies produce both castes sexually; (2) polygyne queens mate with monogyne males to produce workers, but monogyne queens do not mate with polygyne males; and (3) different asexual/polygyne lineages evidently were founded separately by genetically distinct founder queens, which appear to have originated from the same neighboring monogyne population. Multiple asexual/polygyne genomes are transmitted undiluted in this system, but sterile workers produced with sperm from a sexually-reproducing/monogyne population are necessary for the persistence of these lineages. The intersection of social polymorphism, facultative asexuality, and genetic caste determination marks this population of S. geminata as an embodiment of the diversity of ant reproductive systems and suggests previously unknown connections between these phenomena.
•Multi-queen colonies of a fire ant produce queens asexually but workers sexually•Single-queen colonies produce both queens and workers sexually•Queens in multi-queen colonies require sperm from single-queen colony males to produce workers•Distinct asexual/multi-queen lineages may stem from a sexual/single-queen population
Lacy et al. describe a socially polymorphic population of an ant in which multi-queen colonies produce queens asexually but produce workers sexually via matings with males from the sexually-reproducing single-queen social form. Two distinct asexual lineages from multi-queen colonies likely originated from the same sexual single-queen population.
RATIONALE:The developing heart requires both mechanical load and vascularization to reach its proper size, yet the regulation of human heart growth by these processes is poorly understood.
...OBJECTIVE:We seek to elucidate the responses of immature human myocardium to mechanical load and vascularization using tissue engineering approaches.
METHODS AND RESULTS:Using human embryonic stem cell and human induced pluripotent stem cell–derived cardiomyocytes in a 3-dimensional collagen matrix, we show that uniaxial mechanical stress conditioning promotes 2-fold increases in cardiomyocyte and matrix fiber alignment and enhances myofibrillogenesis and sarcomeric banding. Furthermore, cyclic stress conditioning markedly increases cardiomyocyte hypertrophy (2.2-fold) and proliferation rates (21%) versus unconditioned constructs. Addition of endothelial cells enhances cardiomyocyte proliferation under all stress conditions (14% to 19%), and addition of stromal supporting cells enhances formation of vessel-like structures by ≈10-fold. Furthermore, these optimized human cardiac tissue constructs generate Starling curves, increasing their active force in response to increased resting length. When transplanted onto hearts of athymic rats, the human myocardium survives and forms grafts closely apposed to host myocardium. The grafts contain human microvessels that are perfused by the host coronary circulation.
CONCLUSIONS:Our results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.
We present measurements of the density, hydraulic conductivity, and specific discharge of a widespread firn aquifer in Antarctica, within the Wilkins Ice Shelf. At the field site, the aquifer is ...16.2 m thick, starting at 13.4 m from the snow surface and transitioning from water‐saturated firn to ice at 29.6 m. Hydraulic conductivity derived from slug tests show a geometric mean value of 1.4 ± 1.2 × 10−4 m s−1, equivalent to permeability of 2.6 ± 2.2 × 10−11 m2. A borehole dilution test indicates an average specific discharge value of 1.9 ± 2.8 × 10−6 m s−1. Ground‐penetrating radar profiles and a groundwater flow model show the aquifer is draining laterally into a large nearby rift. Our findings indicate that the firn aquifer in the vicinity of the field site is likely not in a steady state and its presence likely contributed to past ice shelf instability.
Plain Language Summary
Firn aquifers occur in areas of high melt and snow accumulation when meltwater percolates into firn (compacted snow older than 1 year) pore space and is stored throughout the winter without refreezing. In December 2018, a field team traveled to the Wilkins Ice Shelf on the Antarctic Peninsula and drilled into an aquifer. We used a combination of hydrology and ground‐penetrating radar measurements to show that water is flowing laterally through porous buried snow and draining into a nearby rift. Firn aquifers are important since they allow meltwater to be stored at depth, possibly running off into cracks, crevasses, or rifts and increasing fracture depth, thereby leading to ice shelf destabilization.
Key Points
An extensive perennial firn aquifer within the Wilkins Ice Shelf is characterized for its hydrologic properties
Field data and modeling show the aquifer has high permeability and is flowing into a nearby rift
Past disintegration events on the Wilkins Ice Shelf with hydrofracture characteristics are likely a result of the aquifer's presence
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