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"Lucas, P"
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Television history, the Peabody Archive, and cultural memory
\"Television History, The Peabody Archive, and Cultural Memory is the product of a multiyear collaboration between the Peabody Awards program and over a dozen media scholars with the intent to uncover, explore, and analyze historical television programming contained in the Peabody Awards archives at the University of Georgia. It is an intentional effort to look both wider and deeper than the well-known canon of U.S. broadcast history that dominates popular memory of the relationship of television to American society. The Peabody Archive is especially suited to this project because it is an archive of programming produced and submitted not just by the big networks in New York or Los Angeles, but by stations and media producers across the nation and, more recently, around the world. This project asks, how might these programs change our understanding of television's past, and impact the ways we think about television's present and future? What new questions can we ask and what new approaches should we take as a result of seeing and experiencing this programming? The contributions in this volume offer a dramatic range of approaches for how scholars can productively engage the archive's media and physical holdings to examine and reconsider television history\"-- Provided by publisher.
Book
Universal microbial reworking of dissolved organic matter along environmental gradients
Soils are losing increasing amounts of carbon annually to freshwaters as dissolved organic matter (DOM), which, if degraded, can offset their carbon sink capacity. However, the processes underlying DOM degradation across environments are poorly understood. Here we show DOM changes similarly along soil-aquatic gradients irrespective of environmental differences. Using ultrahigh-resolution mass spectrometry, we track DOM along soil depths and hillslope positions in forest catchments and relate its composition to soil microbiomes and physico-chemical conditions. Along depths and hillslopes, we find carbohydrate-like and unsaturated hydrocarbon-like compounds increase in abundance-weighted mass, and the expression of genes essential for degrading plant-derived carbohydrates explains >50% of the variation in abundance of these compounds. These results suggest that microbes transform plant-derived compounds, leaving DOM to become increasingly dominated by the same (i.e., universal), difficult-to-degrade compounds as degradation proceeds. By synthesising data from the land-to-ocean continuum, we suggest these processes generalise across ecosystems and spatiotemporal scales. Such general degradation patterns can help predict DOM composition and reactivity along environmental gradients to inform management of soil-to-stream carbon losses.
Soils combat climate change by storing carbon but lose considerable amounts of carbon into downstream waters. Here a general process for how microbes transform carbon across soil-to-stream to impact its persistence in the natural environment is demonstrated.
Journal Article
The microbiome extends host evolutionary potential
The microbiome shapes many host traits, yet the biology of microbiomes challenges traditional evolutionary models. Here, we illustrate how integrating the microbiome into quantitative genetics can help untangle complexities of host-microbiome evolution. We describe two general ways in which the microbiome may affect host evolutionary potential: by shifting the mean host phenotype and by changing the variance in host phenotype in the population. We synthesize the literature across diverse taxa and discuss how these scenarios could shape the host response to selection. We conclude by outlining key avenues of research to improve our understanding of the complex interplay between hosts and microbiomes.
The microbiome is becoming recognized as a key determinant of host phenotype. Here, Henry et al. present a framework for building our understanding of how the microbiome also influences host evolution, review empirical examples and research approaches, and highlight emerging questions.
Journal Article
CCR5 promotes the migration of pathological CD8+ T cells to the leishmanial lesions
Cytolytic CD8 + T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8 + T cell migration to the lesion that could be targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5, Leishmania- infected Rag1 -/- mice were reconstituted with CCR5 -/- CD8 + T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8 + T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8 + T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8 + T cell-mediated pathology.
Journal Article
A Railway Timetable Rescheduling Approach for Handling Large-Scale Disruptions
On a daily basis, large-scale disruptions require infrastructure managers and railway operators to reschedule their railway timetables together with their rolling stock and crew schedules. This research focuses on timetable rescheduling for passenger train services on a macroscopic level in a railway network. An integer linear programming model is formulated for solving the timetable rescheduling problem, which minimizes the number of cancelled and delayed train services while adhering to infrastructure and rolling stock capacity constraints. The possibility of rerouting train services to reduce the number of cancelled and delayed train services is also considered. In addition, all stages of the disruption management process (from the start of the disruption to the time the normal situation is restored) are taken into account. Computational tests of the described model on a heavily used part of the Dutch railway network show that the model is able to find optimal solutions in short computation times. This makes the approach applicable for use in practice.
Journal Article
CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production
Deregulated CD8+ T cell cytotoxicity plays a central role in enhancing disease severity in several conditions. However, we have little understanding of the mechanisms by which immunopathology develops as a consequence of cytotoxicity. Using murine models of inflammation induced by the protozoan parasite leishmania, and data obtained from patients with cutaneous leishmaniasis, we uncovered a previously unrecognized role for NLRP3 inflammasome activation and IL-1β release as a detrimental consequence of CD8+ T cell-mediated cytotoxicity, ultimately resulting in chronic inflammation. Critically, pharmacological blockade of NLRP3 or IL-1β significantly ameliorated the CD8+ T cell-driven immunopathology in leishmania-infected mice. Confirming the relevance of these findings to human leishmaniasis, blockade of the NLRP3 inflammasome in skin biopsies from leishmania-infected patients prevented IL-1β release. Thus, these studies link CD8+ T cell cytotoxicity with inflammasome activation and reveal novel avenues of treatment for cutaneous leishmaniasis, as well as other of diseases where CD8+ T cell-mediated cytotoxicity induces pathology.
Journal Article
Posttransplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression
Posttransplantation cyclophosphamide (PTCy) recently has had a marked impact on human allogeneic hematopoietic cell transplantation (HCT). Yet our understanding of how PTCy prevents graft-versus- host disease (GVHD) largely has been extrapolated from MHC-matched murine skin-allografting models that were highly contextual in their efficacy. Herein, we developed a T cell-replete, MHC-haploidentical, murine HCT model (B6C3F'WB6D2F1) to test the putative underlying mechanisms: alloreactive T cell elimination, alloreactive T cell intrathymic clonal deletion, and suppressor T cell induction. In this model and as confirmed in four others, PTCy did not eliminate alloreactive T cells identified using either specific V[beta]s or the 2C or 4C T cell receptors. Furthermore, the thymus was not necessary for PTCy's efficacy. Rather, PTCy induced alloreactive T cell functional impairment, which was supported by highly active suppressive mechanisms established within one day after PTCy that were sufficient to prevent new donor T cells from causing GVHD. These suppressive mechanisms included the rapid, preferential recovery of [CD4.sup.+][CD25.sup.+][Foxp3.sup.+] regulatory T cells, including those that were alloantigen specific, which served an increasingly critical function over time. Our results prompt a paradigm shift in our mechanistic understanding of PTCy. These results have direct clinical implications for understanding tolerance induction and for rationally developing novel strategies to improve patient outcomes.
Journal Article
Continuous Three-Dimensional Control of a Virtual Helicopter Using a Motor Imagery Based Brain-Computer Interface
Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications.
Journal Article
Impact of phages on soil bacterial communities and nitrogen availability under different assembly scenarios
Bacteriophages, the viruses infecting bacteria, are biological entities that can control their host populations. The ecological relevance of phages for microbial systems has been widely explored in aquatic environments, but the current understanding of the role of phages in terrestrial ecosystems remains limited. Here, our objective was to quantify the extent to which phages drive the assembly and functioning of soil bacterial communities. We performed a reciprocal transplant experiment using natural and sterilized soil incubated with different combinations of two soil microbial communities, challenged against native and non-native phage suspensions as well as against a cocktail of phage isolates. We tested three different community assembly scenarios by adding phages: (a) during soil colonization, (b) after colonization, and (c) in natural soil communities. One month after inoculation with phage suspensions, bacterial communities were assessed by 16S rRNA amplicon gene sequencing.
Journal Article