Decoding Polo-like kinase 1 signaling along the kinetochore–centromere axis

Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet its spatial coordination is obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted active Plk1 to discrete subcompartments within the kinetochore-centromere axis using chemical genetics and decoded functional and phosphoproteomic signatures of each. We observe distinct phosphoproteomic and functional roles, suggesting that Plk1 exists and functions in discrete pools along this axis. Deep within the centromere, Plk1 operates to assure proper chromosome alignment and segregation. Thus, Plk1 at the kinetochore is a conglomerate of an observable bulk pool coupled with additional functional pools below the threshold of microscopic detection/resolution. Although complex, this multiplicity of locales provides an opportunity to decouple functional and phosphoproteomic signatures for a comprehensive understanding of Plk1’s kinetochore functions

Characterization Of Inpaint Residuals In Interferometric Measurements of the Epoch Of Reionization

Radio Frequency Interference (RFI) is one of the systematic challenges preventing 21cm interferometric instruments from detecting the Epoch of Reionization. To mitigate the effects of RFI on data analysis pipelines, numerous inpaint techniques have been developed to restore RFI corrupted data. We examine the qualitative and quantitative errors introduced into the visibilities and power spectrum due to inpainting. We perform our analysis on simulated data as well as real data from the Hydrogen Epoch of Reionization Array (HERA) Phase 1 upper limits. We also introduce a convolutional neural network that capable of inpainting RFI corrupted data in interferometric instruments. We train our network on simulated data and show that our network is capable at inpainting real data without requiring to be retrained. We find that techniques that incorporate high wavenumbers in delay space in their modeling are best suited for inpainting over narrowband RFI. We also show that with our fiducial parameters Discrete Prolate Spheroidal Sequences (DPSS) and CLEAN provide the best performance for intermittent ``narrowband'' RFI while Gaussian Progress Regression (GPR) and Least Squares Spectral Analysis (LSSA) provide the best performance for larger RFI gaps. However we caution that these qualitative conclusions are sensitive to the chosen hyperparameters of each inpainting technique. We find these results to be consistent in both simulated and real visibilities. We show that all inpainting techniques reliably reproduce foreground dominated modes in the power spectrum. Since the inpainting techniques should not be capable of reproducing noise realizations, we find that the largest errors occur in the noise dominated delay modes. We show that in the future, as the noise level of the data comes down, CLEAN and DPSS are most capable of reproducing the fine frequency structure in the visibilities of HERA data.Comment: 26 pages, 18 figure

Search for the Epoch of Reionisation with HERA: Upper Limits on the Closure Phase Delay Power Spectrum

Radio interferometers aiming to measure the power spectrum of the redshifted 21 cm line during the Epoch of Reionisation (EoR) need to achieve an unprecedented dynamic range to separate the weak signal from overwhelming foreground emissions. Calibration inaccuracies can compromise the sensitivity of these measurements to the effect that a detection of the EoR is precluded. An alternative to standard analysis techniques makes use of the closure phase, which allows one to bypass antenna-based direction-independent calibration. Similarly to standard approaches, we use a delay spectrum technique to search for the EoR signal. Using 94 nights of data observed with Phase I of the Hydrogen Epoch of Reionization Array (HERA), we place approximate constraints on the 21 cm power spectrum at $z=7.7$. We find at 95% confidence that the 21 cm EoR brightness temperature is $\le$(372)$^2$ "pseudo" mK$^2$ at 1.14 "pseudo" $h$ Mpc$^{-1}$, where the "pseudo" emphasises that these limits are to be interpreted as approximations to the actual distance scales and brightness temperatures. Using a fiducial EoR model, we demonstrate the feasibility of detecting the EoR with the full array. Compared to standard methods, the closure phase processing is relatively simple, thereby providing an important independent check on results derived using visibility intensities, or related.Comment: 16 pages, 14 figures, accepted for publication by MNRA

Simulating rewetting events in intermittent rivers and ephemeral streams: a global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56‐98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached organic matter. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events

Improved Constraints on the 21 cm EoR Power Spectrum and the X-Ray Heating of the IGM with HERA Phase I Observations

We report the most sensitive upper limits to date on the 21 cm epoch of reionization power spectrum using 94 nights of observing with Phase I of the Hydrogen Epoch of Reionization Array (HERA). Using similar analysis techniques as in previously reported limits (HERA Collaboration 2022a), we find at 95% confidence that $\Delta^2(k = 0.34$ $h$ Mpc$^{-1}$) $\leq 457$ mK$^2$ at $z = 7.9$ and that $\Delta^2 (k = 0.36$ $h$ Mpc$^{-1}) \leq 3,496$ mK$^2$ at $z = 10.4$, an improvement by a factor of 2.1 and 2.6 respectively. These limits are mostly consistent with thermal noise over a wide range of $k$ after our data quality cuts, despite performing a relatively conservative analysis designed to minimize signal loss. Our results are validated with both statistical tests on the data and end-to-end pipeline simulations. We also report updated constraints on the astrophysics of reionization and the cosmic dawn. Using multiple independent modeling and inference techniques previously employed by HERA Collaboration (2022b), we find that the intergalactic medium must have been heated above the adiabatic cooling limit at least as early as $z = 10.4$, ruling out a broad set of so-called "cold reionization" scenarios. If this heating is due to high-mass X-ray binaries during the cosmic dawn, as is generally believed, our result's 99% credible interval excludes the local relationship between soft X-ray luminosity and star formation and thus requires heating driven by evolved low-metallicity stars.Comment: 57 pages, 37 figures. Updated to match the accepted ApJ version. Corresponding author: Joshua S. Dillo

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

Validation of the HERA Phase I Epoch of Reionization 21 cm Power Spectrum Software Pipeline

We describe the validation of the HERA Phase I software pipeline by a series of modular tests, building up to an end-to-end simulation. The philosophy of this approach is to validate the software and algorithms used in the Phase I upper-limit analysis on wholly synthetic data satisfying the assumptions of that analysis, not addressing whether the actual data meet these assumptions. We discuss the organization of this validation approach, the specific modular tests performed, and the construction of the end-to-end simulations. We explicitly discuss the limitations in scope of the current simulation effort. With mock visibility data generated from a known analytic power spectrum and a wide range of realistic instrumental effects and foregrounds, we demonstrate that the current pipeline produces power spectrum estimates that are consistent with known analytic inputs to within thermal noise levels (at the 2σ level) for k > 0.2h Mpc-1 for both bands and fields considered. Our input spectrum is intentionally amplified to enable a strong "detection" at k ~ 0.2 h Mpc-1-at the level of ~25σ-with foregrounds dominating on larger scales and thermal noise dominating at smaller scales. Our pipeline is able to detect this amplified input signal after suppressing foregrounds with a dynamic range (foreground to noise ratio) of ≳107. Our validation test suite uncovered several sources of scale-independent signal loss throughout the pipeline, whose amplitude is well-characterized and accounted for in the final estimates. We conclude with a discussion of the steps required for the next round of data analysis

Effects of model incompleteness on the drift-scan calibration of radio telescopes

Precision calibration poses challenges to experiments probing the redshifted 21-cm signal of neutral hydrogen from the Cosmic Dawn and Epoch of Reionization (z ~ 30-6). In both interferometric and global signal experiments, systematic calibration is the leading source of error. Though many aspects of calibration have been studied, the overlap between the two types of instruments has received less attention. We investigate the sky based calibration of total power measurements with a HERA dish and an EDGES-style antenna to understand the role of autocorrelations in the calibration of an interferometer and the role of sky in calibrating a total power instrument. Using simulations we study various scenarios such as time variable gain, incomplete sky calibration model, and primary beam model. We find that temporal gain drifts, sky model incompleteness, and beam inaccuracies cause biases in the receiver gain amplitude and the receiver temperature estimates. In some cases, these biases mix spectral structure between beam and sky resulting in spectrally variable gain errors. Applying the calibration method to the HERA and EDGES data, we find good agreement with calibration via the more standard methods. Although instrumental gains are consistent with beam and sky errors similar in scale to those simulated, the receiver temperatures show significant deviations from expected values. While we show that it is possible to partially mitigate biases due to model inaccuracies by incorporating a time-dependent gain model in calibration, the resulting errors on calibration products are larger and more correlated. Completely addressing these biases will require more accurate sky and primary beam models