Late Jurassic Paleogeography of the U.S. Cordillera from Detrital Zircon Age and Hafnium Analysis of the Galice Formation, Klamath Mountains, Oregon and California, USA

The Upper Jurassic Galice Formation, a metasedimentary unit in the Western Klamath Mountains, formed within an intra-arc basin prior to and during the Nevadan orogeny. New detrital zircon U-Pb age analyses (N = 11; n = 2792) yield maximum depositional ages (MDA) ranging from ca. 160 Ma to 151 Ma, which span Oxfordian to Kimmeridgian time and overlap Nevadan contractional deformation that began by ca. 157 Ma. Zircon ages indicate a significant North American continental provenance component that is consistent with tectonic models placing the Western Klamath terrane on the continental margin in Late Jurassic time. Hf isotopic analysis of Mesozoic detrital zircon (n = 603) from Galice samples reveals wide-ranging εHf values for Jurassic and Triassic grains, many of which cannot be explained by a proximal source in the Klamath Mountains, thus indicating a complex provenance. New U-Pb ages and Hf data from Jurassic plutons within the Klamath Mountains match some of the Galice Formation detrital zircon, but these data cannot account for the most non-radiogenic Jurassic detrital grains. In fact, the in situ Cordilleran arc record does not provide a clear match for the wide-ranging isotopic signature of Triassic and Jurassic grains. When compiled, Galice samples indicate sources in the Sierra Nevada pre-batholithic framework and retroarc region, older Klamath terranes, and possibly overlap strata from the Blue Mountains and the Insular superterrane. Detrital zircon age spectra from strata of the Upper Jurassic Great Valley Group and Mariposa Formation contain similar age modes, which suggests shared sediment sources. Inferred Galice provenance within the Klamath Mountains and more distal sources suggest that the Galice basin received siliciclastic turbidites fed by rivers that traversed the Klamath-Sierran arc from headwaters in the retroarc region. Thus, the Galice Formation contains a record of active Jurassic magmatism in the continental arc, with significant detrital input from continental sediment sources within and east of the active arc. These westward-flowing river systems remained active throughout the shift in Cordilleran arc tectonics from a transtensional system to the Nevadan contractional system, which is characterized by sediment sourced in uplifts within and east of the arc and the thrusting of older Galice sediments beneath older Klamath terranes to the east

Identity work and the `unemployed' worker: age, disability and the lived experience of the older unemployed

This article seeks to explore how older individuals negotiate and manage their self-identity in relation to work while situated without paid employment. After reviewing the current positions of the older unemployed in the UK, noting the substantial overlap between age and disability, we turn our attention to conceptualizing the lived experiences of individuals through exploring `identity work' as a means of understanding a non-working work identity. Based upon focus group interviews, our empirical analysis focuses on key dimensions of participants' identity practice and how they sought to manage the following social processes: imposed identities; crafting working identities; and contesting unfavourable working identities.The conclusion contextualizes the findings against a backdrop of increasing individualistic discourses underpinning approaches to employability, closes with the policy implications arising from this study, and makes suggestions for future research agendas. </jats:p

Robust, flexible, and scalable tests for Hardy-Weinberg Equilibrium across diverse ancestries

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in datasets comprised of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence datasets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently amongst the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth

TLR2 and TLR4 as Potential Biomarkers of Environmental Particulate Matter Exposed Human Myeloid Dendritic Cells

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution

Social Security Research at the University of Michigan Retirement and Disability Research Center

In 1998, the Social Security Administration established the Retirement Research Consortium to encourage research on topics related to Social Security and the well-being of older Americans, and to foster communication between the academic and policy communities. The Michigan Retirement Research Center (MRRC) participated in the Consortium from its inception until 2019, when the MRRC expanded and became the Michigan Retirement and Disability Research Center. This article surveys a selection of the MRRC’s output over its second 10 years (2008–2017), summarizes its innovative use of new data sources, and highlights several key themes in the center’s research contributions

Time-Dependent c-Myc Transactomes Mapped by Array-Based Nuclear Run-On Reveal Transcriptional Modules in Human B Cells

The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome").We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs.By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network

Association and Linkage of Atopic Dermatitis with Chromosome 13q12–14 and 5q31–33 Markers

Atopic dermatitis is a chronic inflammatory skin disease that affects 10–20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31–33, 6p21.3, 12q15–24.1, 13q12–31, and 14q11.2/14q32.1–32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12–14 and 5q31–33

Activation of Epidermal Toll-Like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair

Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus–derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2−/− mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier

Nanosatellite optical downlink experiment: design, simulation, and prototyping

The nanosatellite optical downlink experiment (NODE) implements a free-space optical communications (lasercom) capability on a CubeSat platform that can support low earth orbit (LEO) to ground downlink rates>10  Mbps. A primary goal of NODE is to leverage commercially available technologies to provide a scalable and cost-effective alternative to radio-frequency-based communications. The NODE transmitter uses a 200-mW 1550-nm master-oscillator power-amplifier design using power-efficient M-ary pulse position modulation. To facilitate pointing the 0.12-deg downlink beam, NODE augments spacecraft body pointing with a microelectromechanical fast steering mirror (FSM) and uses an 850-nm uplink beacon to an onboard CCD camera. The 30-cm aperture ground telescope uses an infrared camera and FSM for tracking to an avalanche photodiode detector-based receiver. Here, we describe our approach to transition prototype transmitter and receiver designs to a full end-to-end CubeSat-scale system. This includes link budget refinement, drive electronics miniaturization, packaging reduction, improvements to pointing and attitude estimation, implementation of modulation, coding, and interleaving, and ground station receiver design. We capture trades and technology development needs and outline plans for integrated system ground testing.United States. National Aeronautics and Space Administration. Research Fellowship ProgramLincoln Laboratory (Lincoln Scholars)Lincoln Laboratory (Military Fellowship Program)Fundación Obra Social de La Caixa (Fellowship)Samsung FellowshipUnited States. Air Force (Assistant Secretary of Defense for Research & Engineering. Contract FAs872105C0002