Estimation and inference for the mediation effect in a time-varying mediation model.

Background: Traditional mediation analysis typically examines the relations among an intervention, a time-invariant mediator, and a time-invariant outcome variable. Although there may be a total effect of the intervention on the outcome, there is a need to understand the process by which the intervention affects the outcome (i.e.

The Four mRNA Bases Have Quite Different (Un)folding Free Energies, Applications to RNA Splicing and Translation Initiation with BindOligoNet.

Expression of mRNA is often regulated by the binding of a small RNA (miRNA, snoRNA, siRNA). While the pairing contribution to the net free energy is well parameterized and can be computed in O(N) time, the cost of removing pre-existing mRNA secondary structure has not received sufficient attention. Conventional methods for computing the unfolding free energy of a target mRNA are costly, scaling like the cube of the number of target bases O(N).

Rapid genomic convergent evolution in experimental populations of Trinidadian guppies ().

Although rapid phenotypic evolution has been documented often, the genomic basis of rapid adaptation to natural environments is largely unknown in multicellular organisms. Population genomic studies of experimental populations of Trinidadian guppies () provide a unique opportunity to study this phenomenon. Guppy populations that were transplanted from high-predation (HP) to low-predation (LP) environments have been shown to evolve toward the phenotypes of naturally colonized LP populations in as few as eight generations.

Family nurture intervention increases term age forebrain EEG activity: A multicenter replication trial.

Objective: This trial (RCT-2) sought to replicate the EEG findings of a randomized controlled trial of Family Nurture Intervention in the NICU (FNI-NICU) (RCT-1) comparing infants receiving standard care (SC) with infants receiving SC plus FNI .

Methods: RCT-2 (NCT02710474) was conducted at two NICUs. Subjects were randomly assigned to receive SC or FNI during their NICU stay.

-event characterization and rejection in point-contact HPGe detectors.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to particles incident on the sensitive passivated and p surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( ) in Ge.

Enhancing Synchronization by Optimal Correlated Noise.

From the flashes of fireflies to Josephson junctions and power infrastructure, networks of coupled phase oscillators provide a powerful framework to describe synchronization phenomena in many natural and engineered systems. Most real-world networks are under the influence of noisy, random inputs, potentially inhibiting synchronization. While noise is unavoidable, here we show that there exist optimal noise patterns which minimize desynchronizing effects and even enhance order.

Searching for HIV and AIDS Health Information in South Africa, 2004-2019: Analysis of Google and Wikipedia Search Trends.

Background: AIDS, caused by HIV, is a leading cause of mortality in Africa. HIV/AIDS is among the greatest public health challenges confronting health authorities, with South Africa having the greatest prevalence of the disease in the world. There is little research into how Africans meet their health information needs on HIV/AIDS online, and this research gap impacts programming and educational responses to the HIV/AIDS pandemic.

"A fly appeared": sable, a classic Drosophila mutation, maps to Yippee, a gene affecting body color, wings, and bristles.

Insect body color is an easily assessed and visually engaging trait that is informative on a broad range of topics including speciation, biomaterial science, and ecdysis. Mutants of the fruit fly Drosophila melanogaster have been an integral part of body color research for more than a century. As a result of this long tenure, backlogs of body color mutations have remained unmapped to their genes, all while their strains have been dutifully maintained, used for recombination mapping, and part of genetics education.

Neuroethology: Regulation of pre-sleep behaviors.

Animals exhibit species-specific behaviors before transitioning from wake to sleep. A new study characterizes pre-sleep behaviors in mice and shows that these behaviors are regulated, at least in part, by neurons in the lateral hypothalamus.

High efficacy of layered controls for reducing exposure to airborne pathogens.

To optimize strategies for curbing the transmission of airborne pathogens, the efficacy of three key controls-face masks, ventilation, and physical distancing-must be well understood. In this study, we used the Quadrature-based model of Respiratory Aerosol and Droplets to quantify the reduction in exposure to airborne pathogens from various combinations of controls. For each combination of controls, we simulated thousands of scenarios that represent the tremendous variability in factors governing airborne transmission and the efficacy of mitigation strategies.

Single-virus assay reveals membrane determinants and mechanistic features of Sendai virus binding.

Sendai virus (SeV, formally murine respirovirus) is a membrane-enveloped, negative-sense RNA virus in the Paramyxoviridae family and is closely related to human parainfluenza viruses. SeV has long been utilized as a model paramyxovirus and has recently gained attention as a viral vector candidate for both laboratory and clinical applications. To infect host cells, SeV must first bind to sialic acid glycolipid or glycoprotein receptors on the host cell surface via its hemagglutinin-neuraminidase (HN) protein.

Natural and Synthetic Suppressor Mutations Defy Stability-Activity Tradeoffs.

Thermodynamic stability represents one important constraint on protein evolution, but the molecular basis for how mutations that change stability impact fitness remains unclear. Here, we demonstrate that a prevalent global suppressor mutation in TEM β-lactamase, M182T, increases fitness by reducing proteolysis . We also show that a synthetic mutation, M182S, can act as a global suppressor and suggest that its absence from natural populations is due to genetic inaccessibility rather than fundamental differences in the protein's stability or activity.

A modified Ricker map and its bursting oscillations.

In our search to understand complex oscillation in discrete dynamic systems, we modify the Ricker map, where one parameter is also a dynamic variable. Using the bistable behavior of the fixed point solution, we analyze two response functions that characterize the change of the dynamic parameter. The 2D map sustains different types of burst oscillations that depend on the response functions.

A tandem duplication in Drosophila melanogaster shows enhanced expression beyond the gene copy number.

Tandem duplicated genes are common features of genomes, but the phenotypic consequences of their origins are not well understood. It is not known whether a simple doubling of gene expression should be expected, or else some other expression outcome. This study describes an experimental framework using engineered deletions to assess any contribution of locally acting cis- and globally acting trans-regulatory factors to expression interactions of particular tandem duplicated genes.

A Classical Formulation of Quantum Theory?

We explore a particular way of reformulating quantum theory in classical terms, starting with phase space rather than Hilbert space, and with actual probability distributions rather than quasiprobabilities. The classical picture we start with is epistemically restricted, in the spirit of a model introduced by Spekkens. We obtain quantum theory only by combining a of restricted classical pictures.

New York City jails: COVID discharge policy, data transparency, and reform.

During the early stages of the COVID-19 pandemic in 2020, Mayor Bill de Blasio ordered the release of individuals incarcerated in New York City jails who were at high risk of contracting the disease and at low risk of committing criminal reoffense. Using public information, we construct and analyze a database of nearly 350,000 incarceration episodes in the city jail system from 2014-2020, paying special attention to what happened during the week of March 23-29, 2020, immediately following the mayor's order. In concordance with de Blasio's stated policy, we find that being discharged during this focus week is associated with a lower probability of readmission as compared to being discharged during the same calendar week in previous years.

Vertical Transmission and Neonatal Outcomes Following Maternal SARS-CoV-2 Infection During Pregnancy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 200 million people worldwide and has likely exposed millions of neonates to SARS-CoV-2 in utero. A large body of literature has examined the possibility of vertical transmission from pregnant women infected with SARS-CoV-2 to their neonates. In this chapter, we review mechanisms of-and evidence for-vertical transmission of SARS-CoV-2, including transplacental, through other biospecimens and breastfeeding, and discuss neonatal outcomes following in utero exposure.

Association of the Implementation of Child Tax Credit Advance Payments With Food Insufficiency in US Households.

Importance: A key component of the American Rescue Plan Act of 2021 included an expansion of the Child Tax Credit with advance payments beginning in July 2021, a "child allowance" that was projected to dramatically reduce child poverty. Food insufficiency has increased markedly during the economic crisis spurred by the COVID-19 pandemic, with disparities among marginalized populations, and may be associated with substantial health care and social costs.

Objective: To assess whether the introduction of advance payments for the Child Tax Credit in mid-July 2021 was associated with changes in food insufficiency in US households with children.

Cell-Type-Specific Circadian Bioluminescence Rhythms in Reporter Mice.

Circadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein ().

Spectacles of Settler Colonial Memory: Archaeological Findings from an Early Twentieth-Century "First" Settlement Pageant and Other Commemorative Terrain in New England.

In 1923, rural New England mill town Dover, New Hampshire, staged a Tercentenary pageant of extraordinary proportions to celebrate its "first" settlement. This public spectacle memorialized a specific, and deeply exclusionary, narrative of English settler colonialism, shaped by social anxieties of the post-First World War United States. Recent archaeological research has found possible remnants from this spectacle on a seventeenth-century site.

The earliest history of eukaryotic life: uncovering an evolutionary story through the integration of biological and geological data.

While there is significant data on eukaryogenesis and the early development of the eukaryotic lineage, major uncertainties regarding their origins and evolution remain, including questions of taxonomy, timing, and paleoecology. Here we examine the origin and diversification of the eukaryotes in the Proterozoic Eon as viewed through fossils, organic biomarkers, molecular clocks, phylogenies, and redox proxies. Our interpretation of the integration of these data suggest that eukaryotes were likely aerobic and established in Proterozoic ecosystems.

Carbon cycle dynamics and ecology revealed by the carbon isotopic composition of single organic microfossils during the Late Devonian Biotic Crisis.

We apply a new approach for the δ C analysis of single organic-walled microfossils (OWM) to three sites in the Appalachian Basin of New York (AB) that span the Late Devonian Biotic Crisis (LDBC). Our data provide new insights into the nature of the Frasnian-Famennian carbon cycle in the AB and also provide possible constraints on the paleoecology of enigmatic OWM ubiquitous in Paleozoic shale successions. The carbon isotope compositions of OWM are consistent with normal marine organic matter of autochthonous origins and range from -32 to -17‰, but average -25‰ across all samples and are consistently C-enriched compared to bulk sediments (δ C ) by ~0-10‰.

Evidence for cumulative cultural evolution in bird song.

In studies of cumulative cultural evolution in non-human animals, the focus is most often on incremental changes that increase the efficacy of an existing form of socially learned behaviour, such as the refinement of migratory pathways. In this paper, we compare the songs of different species to describe patterns of evolution in the acoustic structure of bird songs, and explore the question of what building blocks might underlie cumulative cultural evolution of bird song using a comparative approach. We suggest that three steps occurred: first, imitation of independent sounds, or notes, via social learning; second, the formation of categories of note types; and third, assembling note types into sequences with defined structures.