460 research outputs found

    Poets on Place

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    Out to see America and satisfy his travel bug, W. T. Pfefferle resigned from his position as director of the writing program at Johns Hopkins University and hit the road to interview sixty-two poets about the significance of place in their work. The lively conversations that resulted may surprise with the potential meanings of a seemingly simple concept. This gathering of voices and ideas is illustrated with photo and word portraits from the road and represented with suitable poems. The poets are James Harms, David Citino, Martha Collins, Linda Gregerson, Richard Tillinghast, Orlando Ricardo Menes, Mark Strand, Karen Volkman, Lisa Samuels, Marvin Bell, Michael Dennis Browne, David Allan Evans, David Romtvedt, Sandra Alcosser, Robert Wrigley, Nance Van Winckel, Christopher Howell, Mark Halperin, Jana Harris, Sam Hamill, Barbara Drake, Floyd Skloot, Ralph Angel, Carol Muske-Dukes, David St. John, Sharon Bryan, Donald Revell, Claudia Keelan, Alberto Rios, Richard Shelton, Jane Miller, William Wenthe, Naomi Shihab Nye, Peter Cooley, Miller Williams, Beth Ann Fennelly, Natasha Trethewey, Denise Duhamel, Campbell McGrath, Terrance Hayes, Alan Shapiro, Nikki Giovanni, Charles Wright, Rita Dove, Henry Taylor, Dave Smith, Nicole Cooley, David Lehman, Lucie Brock-Broido, Michael S. Harper, C. D. Wright, Mark Wunderlich, James Cummins, Frederick Smock, Mark Jarman, Carl Phillips, Scott Cairns, Elizabeth Dodd, Jonathan Holden, Bin Ramke, Kenneth Brewer, and Paisley Rekdal.https://digitalcommons.usu.edu/usupress_pubs/1087/thumbnail.jp

    New House

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    Heavy Impurity Confinement in Hybrid Operation Scenario Plasmas with a Rotating 1/1 Continuous Mode

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    In future tokamaks like ITER with tungsten walls, it is imperative to control tungsten accumulation in the core of operational plasmas, especially since tungsten accumulation can lead to radiative collapse and disruption. We investigate the behaviour of tungsten trace impurities in a JET-like hybrid-scenario with both axisymmetric and saturated 1/1 ideal helical-core in the presence of strong plasma rotation. For this purpose, we obtain the equilibria from VMEC and use VENUS-LEVIS, a guiding-centre orbit-following code, to follow heavy impurity particles. In this work, VENUS-LEVIS has been modified to account for strong plasma flows with associated neoclassical effects arising from such flows. We find that the combination of helical core and plasma rotation augments the standard neoclassical inward pinch compared to axisymmetry, and leads to a strong inward pinch of impurities towards the magnetic axis despite the strong outward diffusion provided by the centrifugal force, as frequently observed in experiments

    Do red deer stags (Cervus elaphus) use roar fundamental frequency (F0) to assess rivals?

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    It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations

    Modelling of advanced three-ion ICRF heating and fast ion generation scheme for tokamaks and stellarators

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    Absorption of ion-cyclotron range of frequencies waves at the fundamental resonance is an efficient source of plasma heating and fast ion generation in tokamaks and stellarators. This heating method is planned to be exploited as a fast ion source in the Wendelstein 7-X stellarator. The work presented here assesses the possibility of using the newly developed three-ion species scheme (Kazakov et al (2015) Nucl. Fusion 55 032001) in tokamak and stellarator plasmas, which could offer the capability of generating more energetic ions than the traditional minority heating scheme with moderate input power. Using the SCENIC code, it is found that fast ions in the MeV range of energy can be produced in JET-like plasmas. The RF-induced particle pinch is seen to strongly impact the fast ion pressure profile in particular. Our results show that in typical high-density W7-X plasmas, the three-ion species scheme generates more energetic ions than the more traditional minority heating scheme, which makes three-ion scenario promising for fast-ion confinement studies in W7-X

    A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

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    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

    LKB1/STK11 Inactivation Leads to Expansion of a Prometastatic Tumor Subpopulation in Melanoma

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    Germline mutations in LKB1 (STK11) are associated with the Peutz-Jeghers syndrome (PJS), which includes aberrant mucocutaneous pigmentation, and somatic LKB1 mutations occur in 10% of cutaneous melanoma. By somatically inactivating Lkb1 with K-Ras activation (±p53 loss) in murine melanocytes, we observed variably pigmented and highly metastatic melanoma with 100% penetrance. LKB1 deficiency resulted in increased phosphorylation of the SRC family kinase (SFK) YES, increased expression of WNT target genes, and expansion of a CD24+ cell population, which showed increased metastatic behavior in vitro and in vivo relative to isogenic CD24− cells. These results suggest that LKB1 inactivation in the context of RAS activation facilitates metastasis by inducing an SFK-dependent expansion of a prometastatic, CD24+ tumor subpopulation

    Type I Interferons Link Viral Infection to Enhanced Epithelial Turnover and Repair

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    The host immune system functions constantly to maintain chronic commensal and pathogenic organisms in check. The consequences of these immune responses on host physiology are as yet unexplored, and may have long-term implications in health and disease. We show that chronic viral infection increases epithelial turnover in multiple tissues, and the antiviral cytokines type I interferons (IFNs) mediate this response. Using a murine model with persistently elevated type I IFNs in the absence of exogenous viral infection, the Irgm1−/− mouse, we demonstrate that type I IFNs act through nonepithelial cells, including macrophages, to promote increased epithelial turnover and wound repair. Downstream of type I IFN signaling, the highly related IFN-stimulated genes Apolipoprotein L9a and b activate epithelial proliferation through ERK activation. Our findings demonstrate that the host immune response to chronic viral infection has systemic effects on epithelial turnover through a myeloid-epithelial circuit

    E6 and E7 from Beta Hpv38 Cooperate with Ultraviolet Light in the Development of Actinic Keratosis-Like Lesions and Squamous Cell Carcinoma in Mice

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    Cutaneous beta human papillomavirus (HPV) types appear to be involved in the development of non-melanoma skin cancer (NMSC); however, it is not entirely clear whether they play a direct role. We have previously shown that E6 and E7 oncoproteins from the beta HPV type 38 display transforming activities in several experimental models. To evaluate the possible contribution of HPV38 in a proliferative tissue compartment during carcinogenesis, we generated a new transgenic mouse model (Tg) where HPV38 E6 and E7 are expressed in the undifferentiated basal layer of epithelia under the control of the Keratin 14 (K14) promoter. Viral oncogene expression led to increased cellular proliferation in the epidermis of the Tg animals in comparison to the wild-type littermates. Although no spontaneous formation of tumours was observed during the lifespan of the K14 HPV38 E6/E7-Tg mice, they were highly susceptible to 7,12-dimethylbenz(a)anthracene (DMBA)/12-0-tetradecanoylphorbol-13-acetate (TPA) two-stage chemical carcinogenesis. In addition, when animals were exposed to ultraviolet light (UV) irradiation, we observed that accumulation of p21WAF1 and cell-cycle arrest were significantly alleviated in the skin of Tg mice as compared to wild-type controls. Most importantly, chronic UV irradiation of Tg mice induced the development of actinic keratosis-like lesions, which are considered in humans as precursors of squamous cell carcinomas (SCC), and subsequently of SCC in a significant proportion of the animals. In contrast, wild-type animals subjected to identical treatments did not develop any type of skin lesions. Thus, the oncoproteins E6 and E7 from beta HPV38 significantly contribute to SCC development in the skin rendering keratinocytes more susceptible to UV-induced carcinogenesis
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