Showing papers by "University of Wisconsin–Milwaukee published in 2021"

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Abstract: The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1 In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals) These rare variants provide insights into mutational processes and recent human evolutionary history The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 001% The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history

Population Properties of Compact Objects from the Second LIGO-Virgo Gravitational-Wave Transient Catalog

Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.

Observation of Gravitational Waves from Two Neutron Star–Black Hole Coalescences

Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.

A Population-Based Study of Genes Previously Implicated in Breast Cancer

Abstract: Background Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and...

A glycan gate controls opening of the SARS-CoV-2 spike protein.

Abstract: SARS-CoV-2 infection is controlled by the opening of the spike protein receptor binding domain (RBD), which transitions from a glycan-shielded 'down' to an exposed 'up' state to bind the human angiotensin-converting enzyme 2 receptor and infect cells. While snapshots of the 'up' and 'down' states have been obtained by cryo-electron microscopy and cryo-electron tomagraphy, details of the RBD-opening transition evade experimental characterization. Here over 130 µs of weighted ensemble simulations of the fully glycosylated spike ectodomain allow us to characterize more than 300 continuous, kinetically unbiased RBD-opening pathways. Together with ManifoldEM analysis of cryo-electron microscopy data and biolayer interferometry experiments, we reveal a gating role for the N-glycan at position N343, which facilitates RBD opening. Residues D405, R408 and D427 also participate. The atomic-level characterization of the glycosylated spike activation mechanism provided herein represents a landmark study for ensemble pathway simulations and offers a foundation for understanding the fundamental mechanisms of SARS-CoV-2 viral entry and infection.

A gravitational-wave measurement of the Hubble constant following the second observing run of Advanced LIGO and Virgo

Abstract: This paper presents the gravitational-wave measurement of the Hubble constant (H 0) using the detections from the first and second observing runs of the Advanced LIGO and Virgo detector network. The presence of the transient electromagnetic counterpart of the binary neutron star GW170817 led to the first standard-siren measurement of H 0. Here we additionally use binary black hole detections in conjunction with galaxy catalogs and report a joint measurement. Our updated measurement is H 0 = km s−1 Mpc−1 (68.3% of the highest density posterior interval with a flat-in-log prior) which is an improvement by a factor of 1.04 (about 4%) over the GW170817-only value of km s−1 Mpc−1. A significant additional contribution currently comes from GW170814, a loud and well-localized detection from a part of the sky thoroughly covered by the Dark Energy Survey. With numerous detections anticipated over the upcoming years, an exhaustive understanding of other systematic effects are also going to become increasingly important. These results establish the path to cosmology using gravitational-wave observations with and without transient electromagnetic counterparts.

Robust multi-objective optimal design of islanded hybrid system with renewable and diesel sources/stationary and mobile energy storage systems

Abstract: Planning of an islanded hybrid system (IHS) with different sources and storages to supply clean, flexible, and highly reliable energy at consumption sites is of high importance. To this end, this paper presents the design of an IHS with a wind turbine, photovoltaic, diesel generator, and stationary (battery) and mobile (electrical vehicles) energy storage systems (ESS). The proposed method includes a multi-objective optimization to minimize the total cost of construction, maintenance, and operation of sources and ESSs within the IHS and the emission level of the system using two separate objective functions. The problem is subject to operational and planning constraints of sources and ESSs and power. Employing the Pareto optimization technique based on the e-constraint method forms a single-objective optimization problem for the proposed design. The problem involves uncertainties of load, renewable energy, and energy demand of mobile ESSs and has a nonlinear form. Adaptive robust optimization based on a hybrid meta-heuristic algorithm that utilizes a combination of the sine-cosine algorithm (SCA) and crow search algorithm (CSA) is proposed to achieve an optimal robust structure for the suggested scheme. In this scheme, operation model of the mobile storage systems in the IHS considering the uncertainties prediction errors and its model using HMA-based ARO besides adopting the HMA to achieve a unique optimal solution are among the novelties of this research. Eventually, considering the climate data and energy consumption of a region in Rafsanjan, Iran, capabilities of the method in extracting a robust IHS for sources and ESSs are validated depending on optimal economic and environmental conditions. The HMA succeeds to reach an optimal solution with an SD of 0.92% in the final response and this underlines its capability in achieving approximate conditions of unique responsiveness. The proposed scheme with proper planning and operation of sources and storages in the form of a HIS finds optimal values for economic and environmental conditions so that the difference between pollution and cost values from its minimum values at the compromise point is roughly 22%. For 17% uncertainty parameters prediction errors, the scheme obtains a robust structure for the IHS.

Upper limits on the isotropic gravitational-wave background from Advanced LIGO and Advanced Virgo’s third observing run

Abstract: We report results of a search for an isotropic gravitational-wave background (GWB) using data from Advanced LIGO’s and Advanced Virgo’s third observing run (O3) combined with upper limits from the earlier O1 and O2 runs. Unlike in previous observing runs in the advanced detector era, we include Virgo in the search for the GWB. The results of the search are consistent with uncorrelated noise, and therefore we place upper limits on the strength of the GWB. We find that the dimensionless energy density Ω GW ≤ 5.8 × 10 − 9 at the 95% credible level for a flat (frequency-independent) GWB, using a prior which is uniform in the log of the strength of the GWB, with 99% of the sensitivity coming from the band 20–76.6 Hz; Ω GW ( f ) ≤ 3.4 × 10 − 9 at 25 Hz for a power-law GWB with a spectral index of 2 / 3 (consistent with expectations for compact binary coalescences), in the band 20–90.6 Hz; and Ω GW ( f ) ≤ 3.9 × 10 − 10 at 25 Hz for a spectral index of 3, in the band 20–291.6 Hz. These upper limits improve over our previous results by a factor of 6.0 for a flat GWB, 8.8 for a spectral index of 2 / 3 , and 13.1 for a spectral index of 3. We also search for a GWB arising from scalar and vector modes, which are predicted by alternative theories of gravity; we do not find evidence of these, and place upper limits on the strength of GWBs with these polarizations. We demonstrate that there is no evidence of correlated noise of magnetic origin by performing a Bayesian analysis that allows for the presence of both a GWB and an effective magnetic background arising from geophysical Schumann resonances. We compare our upper limits to a fiducial model for the GWB from the merger of compact binaries, updating the model to use the most recent data-driven population inference from the systems detected during O3a. Finally, we combine our results with observations of individual mergers and show that, at design sensitivity, this joint approach may yield stronger constraints on the merger rate of binary black holes at z ≳ 2 than can be achieved with individually resolved mergers alone.

Evaluation of Sampling, Analysis, and Normalization Methods for SARS-CoV-2 Concentrations in Wastewater to Assess COVID-19 Burdens in Wisconsin Communities

Abstract: Wastewater surveillance for SARS-CoV-2 provides an approach for assessing the infection burden across a sewer service area. For these data to be useful for public health, measurement variability and the relationship to case data need to be established. We determined SARS-CoV-2 RNA concentrations in the influent of 12 wastewater treatment plants from August 2020 to January 2021. Technical replicates for N1 gene concentrations showed a relative standard deviation of 24%, suggesting it is possible to track relatively small (similar to 30%) changes in SARS-CoV-2 concentrations over time. COVID-19 cases were correlated significantly (rho >= 0.70) to wastewater SARS-CoV-2 RNA concentrations across large and small service areas, with weaker relationships (rho >= 0.59) in two communities. SARS-CoV-2 concentrations normalized to per capita slightly improved correlations to COVID-19 incidence, but normalizing to a spiked recovery control (BCoV) or a fecal marker (PMMoV or HF183) reduced correlations for a number of plants. Daily sampling demonstrated that a minimum of two samples collected per week were needed to maintain accuracy in trend analysis. The differences in the strength of SARS-CoV-2 relationships to COVID-19 incidence and the effect of normalization on these data among communities demonstrate that rigorous validation should be performed at individual sites where wastewater surveillance programs are implemented.

The crucial role of genome-wide genetic variation in conservation.

Abstract: The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on conserving genome-wide genetic variation, and that the field should instead focus on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations toward extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide genetic variation on long-term population viability will only worsen the biodiversity crisis.

Gravitational-wave physics and astronomy in the 2020s and 2030s

Abstract: The 100 years since the publication of Albert Einstein’s theory of general relativity saw significant development of the understanding of the theory, the identification of potential astrophysical sources of sufficiently strong gravitational waves and development of key technologies for gravitational-wave detectors. In 2015, the first gravitational-wave signals were detected by the two US Advanced LIGO instruments. In 2017, Advanced LIGO and the European Advanced Virgo detectors pinpointed a binary neutron star coalescence that was also seen across the electromagnetic spectrum. The field of gravitational-wave astronomy is just starting, and this Roadmap of future developments surveys the potential for growth in bandwidth and sensitivity of future gravitational-wave detectors, and discusses the science results anticipated to come from upcoming instruments.

The Legacy of Structural Racism: Associations Between Historic Redlining, Current Mortgage Lending, and Health

Abstract: Structural racism, which is embedded in past and present operations of the U.S. housing market, is a fundamental cause of racial health inequities. We conducted an ecologic study to 1) examine historic redlining in relation to current neighborhood lending discrimination and three key indicators of societal health (mental health, physical health, and infant mortality rate (IMR)) and 2) investigate sustained lending disinvestment as a determinant of current neighborhood health in one of the most hypersegregated metropolitan areas in the United States, Milwaukee, Wisconsin. We calculated weighted historic redlining scores from the proportion of 1930s Home Owners' Loan Corporation residential security grades contained within 2010 census tract boundaries. We combined two lending indicators from 2018 Home Mortgage Disclosure Act data to capture current neighborhood lending discrimination: low lending occurrence and high cost loans (measured via loan rate spread). Using historic redlining score and current lending discrimination, we created a 4-level hierarchical measure of lending trajectory. In Milwaukee neighborhoods, greater historic redlining was associated with current lending discrimination (OR = 1.73, 95%CI: 1.16, 2.58) and increased prevalence of poor physical health (β = 1.34, 95%CI: 0.40, 2.28) and poor mental health (β = 1.26, 95%CI: 0.51, 2.01). Historic redlining was not associated with neighborhood IMR (β = −0.48, 95%CI: −2.12, 1.15). A graded association was observed between lending trajectory and health: neighborhoods with high sustained disinvestment had worse physical and mental health than neighborhoods with high investment (poor physical health: β = 5.33, 95%CI: 3.05, 7.61; poor mental health: β = 4.32, 95%CI: 2.44, 6.20). IMR was highest in ‘disinvested’ neighborhoods (β = 5.87, 95%CI: 0.52, 11.22). Our findings illustrate ongoing legacies of government sponsored historic redlining. Structural racism, as manifested in historic and current forms of lending disinvestment, predicts poor health in Milwaukee's hypersegregated neighborhoods. We endorse equity focused policies that dismantle and repair the ways racism is entrenched in America's social fabric.

Actualizing Better Health And Health Care For Older Adults.

Abstract: By 2030 more people in the United States will be older than age sixty-five than younger than age five. Our health care system is unprepared for the complexity of caring for a heterogenous population of older adults-a problem that has been magnified by the coronavirus disease 2019 (COVID-19) pandemic. Here, as part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2021 initiative, we identify six vital directions to improve the care and quality of life for all older Americans. The next administration must create an adequately prepared workforce; strengthen the role of public health; remediate disparities and inequities; develop, evaluate, and implement new approaches to care delivery; allocate resources to achieve patient-centered care and outcomes, including palliative and end-of-life care; and redesign the structure and financing of long-term services and supports. If these priorities are addressed proactively, an infrastructure can be created that promotes better health and equitable, goal-directed care that recognizes the preferences and needs of older adults.

Review on organosulfur materials for rechargeable lithium batteries

Abstract: Organic electrode materials have been considered as promising candidates for the next generation rechargeable battery systems due to their high theoretical capacity, versatility, and environmentally friendly nature. Among them, organosulfur compounds have been receiving more attention in conjunction with the development of lithium–sulfur batteries. Usually, organosulfide electrodes can deliver a relatively high theoretical capacity based on reversible breakage and formation of disulfide (S–S) bonds. In this review, we provide an overview of organosulfur materials for rechargeable lithium batteries, including their molecular structural design, structure related electrochemical performance study and electrochemical performance optimization. In addition, recent progress of advanced characterization techniques for investigation of the structure and lithium storage mechanism of organosulfur electrodes are elaborated. To further understand the perspective application, the additive effect of organosulfur compounds for lithium metal anodes, sulfur cathodes and high voltage inorganic cathode materials are reviewed with typical examples. Finally, some remaining challenges and perspectives of the organosulfur compounds as lithium battery components are also discussed. This review is intended to serve as general guidance for researchers to facilitate the development of organosulfur compounds.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO–Virgo Observing Run

Abstract: We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions A template-based search for short-duration transient signals does not yield a detection We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gμ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models Additionally, we develop and test a third model that interpolates between these two models Our results improve upon the previous LIGO-Virgo constraints on Gμ by 1 to 2 orders of magnitude depending on the model that is tested In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gμ≲4×10^{-15} In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models

Estimating the Impact of “Humanizing” Customer Service Chatbots

Abstract: In this work, we investigate how applying human-like characteristics to customer service chatbots can influence retail outcomes. This is an important managerial question as creating effective chatb...

Multicomponent superconducting order parameter in UTe 2

Abstract: An unconventional superconducting state was recently discovered in uranium ditelluride (UTe2), in which spin-triplet superconductivity emerges from the paramagnetic normal state of a heavy-fermion material. The coexistence of magnetic fluctuations and superconductivity, together with the crystal structure of this material, suggests that a distinctive set of symmetries, magnetic properties, and topology underlie the superconducting state. Here, we report observations of a nonzero polar Kerr effect and of two transitions in the specific heat upon entering the superconducting state, which together suggest that the superconductivity in UTe2 is characterized by a two-component order parameter that breaks time-reversal symmetry. These data place constraints on the symmetries of the order parameter and inform the discussion on the presence of topological superconductivity in UTe2.

Field-induced transition within the superconducting state of CeRh2As2

Abstract: Materials with multiple superconducting phases are rare. Here, we report the discovery of two-phase unconventional superconductivity in CeRh2As2 Using thermodynamic probes, we establish that the superconducting critical field of its high-field phase is as high as 14 tesla, even though the transition temperature is only 0.26 kelvin. Furthermore, a transition between two different superconducting phases is observed in a c axis magnetic field. Local inversion-symmetry breaking at the cerium sites enables Rashba spin-orbit coupling alternating between the cerium sublayers. The staggered Rashba coupling introduces a layer degree of freedom to which the field-induced transition and high critical field seen in experiment are likely related.

Topological band and superconductivity in UTe 2

Abstract: $\mathrm{U}{\mathrm{Te}}_{2}$ is a likely spin-triplet superconductor that also exhibits evidence for chiral Majorana edge states. A characteristic structural feature of $\mathrm{U}{\mathrm{Te}}_{2}$ is inversion-symmetry related pairs of U atoms, forming rungs of ladders. Here we show how each rung's two sublattice degrees of freedom play a key role in understanding the electronic structure and the origin of superconductivity. In particular, $\mathrm{DFT}+U$ calculations generically reveal a topological band near the chemical potential originating from a band inversion associated with $5f$ electrons residing on these rungs, necessitating a microscopic description that includes these rung degrees of freedom. Furthermore, we show that a previously identified strong ferromagnetic interaction within a U-U rung leads to a pseudospin-triplet superconducting state that accounts for a nonzero polar Kerr angle, the observed magnetic field-temperature phase diagrams, and nodal Weyl fermions. Our analysis may also be relevant for other U-based superconductors.