TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA

The replication-dependent histone mRNAs end in a stem–loop instead of the poly(A) tail present at the 3′ end of all other cellular mRNAs. Following processing, the 3′ end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem–loop, and this length is maintained by addition of nontemplated uridines if the mRNA is further trimmed by 3′hExo. These mRNAs are tightly cell-cycle regulated, and a critical regulatory step is rapid degradation of the histone mRNAs when DNA replication is inhibited. An initial step in histone mRNA degradation is digestion 2–4 nt into the stem by 3′hExo and uridylation of this intermediate. The mRNA is then subsequently degraded by the exosome, with stalled intermediates being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs have not been definitively identified. Using high-throughput sequencing of histone mRNAs and degradation intermediates, we find that knockdown of TUT7 reduces both the uridylation at the 3′ end as well as uridylation of the major degradation intermediate in the stem. In contrast, knockdown of TUT4 did not alter the uridylation pattern at the 3′ end and had a small effect on uridylation in the stem–loop during histone mRNA degradation. Knockdown of 3′hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3′hExo function together in trimming and uridylating histone mRNAs

Enabling hotspot detection and public health response to the COVID-19 pandemic

INTRODUCTION: Public-facing maps of COVID-19 cases, hospital admissions, and deaths are commonly displayed at the state, county, and zip code levels, and low case counts are suppressed to protect confidentiality. Public health authorities are tasked with case identification, contact tracing, and canvasing for educational purposes during a pandemic. Given limited resources, authorities would benefit from the ability to tailor their efforts to a particular neighborhood or congregate living facility. METHODS: We describe the methods of building a real-time visualization of patients with COVID-19-positive tests, which facilitates timely public health response to the pandemic. We developed an interactive street-level visualization that shows new cases developing over time and resolving after 14 days of infection. Our source data included patient demographics (ie, age, race and ethnicity, and sex), street address of residence, respiratory test results, and date of test. RESULTS: We used colored dots to represent infections. The resulting animation shows where new cases developed in the region and how patterns changed over the course of the pandemic. Users can enlarge specific areas of the map and see street-level detail on residential location of each case and can select from demographic overlays and contour mapping options to see high-level patterns and associations with demographics and chronic disease prevalence as they emerge. CONCLUSIONS: Before the development of this tool, local public health departments in our region did not have a means to map cases of disease to the street level and gain real-time insights into the underlying population where hotspots had developed. For privacy reasons, this tool is password-protected and not available to the public. We expect this tool to prove useful to public health departments as they navigate not only COVID-19 pandemic outcomes but also other public health threats, including chronic diseases and communicable disease outbreaks

Gravitational waves: search results, data analysis and parameter estimation

The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity

Devotions for Advent 2022 Canticles of Luke

Each week of this Advent devotional will focus on one of the four Lukan canticles, putting it in its context as well as making connections to other portions of Scripture. At the end of this Advent season, may we, like those who have gone before us, “sing to the Lord, bless his name; tell of his salvation from day to day” (Ps. 96:2). Many thanks to all the CSL and CTSFW students who contributed devotional reflections. A special note of thanks to my counterpart, Zachary Roll, who organized this effort at Concordia Seminary, St. Louis who has been a joy to work with and to get to know. A final note of thanks to Kim Hosier in the print shop and Rev. Dr. Paul Grime for their aid in completing this devotional booklet.https://scholar.csl.edu/osp/1021/thumbnail.jp

The Einstein Toolkit: A Community Computational Infrastructure for Relativistic Astrophysics

We describe the Einstein Toolkit, a community-driven, freely accessible computational infrastructure intended for use in numerical relativity, relativistic astrophysics, and other applications. The Toolkit, developed by a collaboration involving researchers from multiple institutions around the world, combines a core set of components needed to simulate astrophysical objects such as black holes, compact objects, and collapsing stars, as well as a full suite of analysis tools. The Einstein Toolkit is currently based on the Cactus Framework for high-performance computing and the Carpet adaptive mesh refinement driver. It implements spacetime evolution via the BSSN evolution system and general-relativistic hydrodynamics in a finite-volume discretization. The toolkit is under continuous development and contains many new code components that have been publicly released for the first time and are described in this article. We discuss the motivation behind the release of the toolkit, the philosophy underlying its development, and the goals of the project. A summary of the implemented numerical techniques is included, as are results of numerical test covering a variety of sample astrophysical problems.Comment: 62 pages, 20 figure

TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA

The replication-dependent histone mRNAs end in a stem–loop instead of the poly(A) tail present at the 3′ end of all other cellular mRNAs. Following processing, the 3′ end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem–loop, and this length is maintained by addition of nontemplated uridines if the mRNA is further trimmed by 3′hExo. These mRNAs are tightly cell-cycle regulated, and a critical regulatory step is rapid degradation of the histone mRNAs when DNA replication is inhibited. An initial step in histone mRNA degradation is digestion 2–4 nt into the stem by 3′hExo and uridylation of this intermediate. The mRNA is then subsequently degraded by the exosome, with stalled intermediates being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs have not been definitively identified. Using high-throughput sequencing of histone mRNAs and degradation intermediates, we find that knockdown of TUT7 reduces both the uridylation at the 3′ end as well as uridylation of the major degradation intermediate in the stem. In contrast, knockdown of TUT4 did not alter the uridylation pattern at the 3′ end and had a small effect on uridylation in the stem–loop during histone mRNA degradation. Knockdown of 3′hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3′hExo function together in trimming and uridylating histone mRNAs

PHEV real world driving cycle energy and fuel and consumption reduction potential for connected and automated vehicles

This paper presents real-world driving energy and fuel consumption results for the second-generation Chevrolet Volt plug-in hybrid electric vehicle (PHEV). A drive cycle, local to Michigan Technological University, was designed to mimic urban and highway driving test cycles in terms of distance, transients and average velocity, but with significant elevation changes to establish an energy intensive real-world driving cycle for assessing potential energy savings for connected and automated vehicle (CAV) control. The investigation began by establishing baseline and repeatability of energy consumption at various battery states of charge. It was determined that drive cycle energy consumption under a randomized set of boundary conditions varied within 3.6% of mean energy consumption regardless of initial battery state of charge. After completing 30 baseline drive cycles, a design for six sigma (DFSS) L18 array was designed to look at sensi-tivity of a range of parameters to energy consumption as related to connected and automated vehicles to target highest return on engineering development effort. The parameters explored in the DFSS array that showed the most sensitivity, in order of importance, were battery state of charge, vehicle mass, propulsion system thermal conditioning, HVAC setting and driver behavior. Each of these areas are explored for energy savings and discussed briefly in the context of CAV control opportunity for energy savings potential

Risky business: Modeling mortality risk near the urban-wildland interface for a large carnivore

We examined the spatial distribution of 382 black bear (Ursus americanus) mortalities in the Lake Tahoe Basin and Western Great Basin Desert (WGB) in Nevada, USA from 1997 to 2013. Of the 364 mortalities for which we could determine cause of death, vehicle collisions (n = 160) and direct removal of bears by management personnel (n = 132) were the two largest sources of mortality for bears in our study area at the confluence of the Sierra-Nevada Mountains and the Great Basin Desert. Here we use logistic regression and resource selection probability functions (RSPF) to model probability of mortality in the WGB based on anthropogenic and landscape variables. Further, we assessed the impact of spatial resolution on our analyses and resulting probability of mortality models. Human-induced mortalities of black bears were overwhelmingly concentrated near major roads (defined in our analyses as paved roads with two lanes or more), in the town of Incline Village, Nevada, and along the foothills of the Carson Range east of Lake Tahoe. Our results suggest mortality risk is associated with density of and distance to multiple forest types, human population density, landcover, recreation site density and distance, road density and distance, stream distance, hiking trail density, and waterbody distance. Our model results found environmental variables measured at coarse spatial resolutions such as distance to and density of forest best predicted black bear mortality risk, while anthropogenic variables measured at fine spatial resolutions like distance to and density of recreation site best predicted black bear mortality risk in our study area. Our results demonstrate that carnivore mortality as a phenomenon likely operates at multiple spatial resolutions and thus considering scale is important for modeling mortality risk on the landscape. Keywords: Carnivore, Black bear, Mortality, RSPF, Scale, Human-wildlife conflic