738 resultados para Peacock, Wayne


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Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER- AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER- AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

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Surface plasmon polaritons usually exist on a few suitable plasmonic materials; however, nanostructured plasmonic metamaterials allow a much broader range of optical properties to be designed. Here, bottom-up and top-down nanostructuring are combined, creating hyperbolic metamaterial-based photonic crystals termed hyperbolic polaritonic crystals, allowing free-space access to the high spatial frequency modes supported by these metamaterials.

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BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling.

METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ(2) tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided.

RESULTS: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts.

CONCLUSIONS: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.

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Laughter and humor are pervasive phenomena in conversa- tional interactions. This paper argues that they function as displays of mind-reading abilities in social interactions–as suggested by the Analogi- cal Peacock Hypothesis (APH). In this view, they are both social bonding signals and can elevate one’s social status. The relational combination of concepts in humor is addressed. However, it is in the inclusion of context and receiver knowledge, required by the APH view, that it contributes the most to existing theories. Taboo and offensive humor are addressed in terms of costly signaling, and implications for human computer inter- action and some possible routes to solutions are suggested.

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Research in the field of sports performance is constantly developing new technology to help extract meaningful data to aid in understanding in a multitude of areas such as improving technical or motor performance. Video playback has previously been extensively used for exploring anticipatory behaviour. However, when using such systems, perception is not active. This loses key information that only emerges from the dynamics of the action unfolding over time and the active perception of the observer. Virtual reality (VR) may be used to overcome such issues. This paper presents the architecture and initial implementation of a novel VR cricket simulator, utilising state of the art motion capture technology (21 Vicon cameras capturing kinematic profile of elite bowlers) and emerging VR technology (Intersense IS-900 tracking combined with Qualisys Motion capture cameras with visual display via Sony Head Mounted Display HMZ-T1), applied in a cricket scenario to examine varying components of decision and action for cricket batters. This provided an experience with a high level of presence allowing for a real-time egocentric view-point to be presented to participants. Cyclical user-testing was carried out, utilisng both qualitative and quantitative approaches, with users reporting a positive experience in use of the system.

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This document contains notes on eight species of birds observed by Arthur T. Wayne in Charleston, South Carolina including the Horned Grebe, the Yellow-crowned Night Heron, Bachman’s Warbler, the Rocky Mountain Orange-crowned Warbler, the Cape May Warbler, the Black-poll Warbler, the Red-breasted Nuthatch, and the Blue-gray Gnatcatcher.

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This document contains notes on seven species of birds observed by Arthur T. Wayne in Charleston, South Carolina including the Yellow-bellied Flycatcher, the Purple Martin, the Black-throated Blue Warbler, Cairn’s Warbler, Grinnell’s Water-Thrush, the Kentucky Warbler, and the Mockingbird.

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This document contains notes on several species of birds observed by Arthur T. Wayne in South Carolina including the Sooty Shearwater, the Harlequin Duck, the Snow Goose, the Blue Goose, the Egret, the Yellow-crowned Night Heron, the Hudsonian Curlew, the Turnstone, the Pigeon Hawk, the Crested Flycatcher, the Bronzed Grackle, the Carolina Grackle, the Ipswich Sparrow, Leconte’s Sparrow, the Mountain Solitary Vireo, Bachman’s Warbler, the Magnolia Warbler, the Black-throated Green Warbler, and the Connecticut Warbler.

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This document contains information on the nest and eggs of the bird, Bachman’s Warbler.

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This document contains information on the breeding season of the American Barn Owl in South Carolina.

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BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, and both have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hour periods from a total of 50 observation days. We measured their exposure to fine particulate matter (PM2.5), ultrafine particles, noise, and the cardiopulmonary health endpoints: blood pressure, pro-inflammatory and pro-thrombotic markers in the blood, lung function and fractional exhaled nitric oxide (FeNO) measured approximately 15 hours post-work. Heart rate variability was assessed during a sleep period approximately 10 hours post-work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased HF and LF power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and non-significantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

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Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

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1969-71 Brock Generals Hockey team. Members from left to right - Back row: Tom Kearney (Trainer), Al Kellogg (Coach), John Hull, Craig Morrison, Gregg Law, Frank Mucci, Dale Andreas, Eric Stevens, Serge Girrard, John Clarey, Wayne Kenyon, Reg Egilsson, Dusty Papke, Randy Oiling (Manager). Front row: Ron Powel, Barry Hopkins, Bruce Wormald, Miller Hicks, Fred Carter, Mike Nicholson, Dick Overholt, Chris Shott. Missing: John O'Brien, Barry Elliot.

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1970-71 Brock Generals Hockey team. The members from left to right - Back row: Tom Kearney (trainer), Joel Finlay, Tony Grey, Gregg Carrigan, Craig Morrison, Pat Moroney, Rick Charron, Jim Swain, Bill Fuller, Barry Hopkins, Mike McNiven, Rick Sullivan, Ed Barszcz, Phil McCann, Randy Oiling (Manager), Al Kellogg (Coach). Front row: Wayne Butt, Ron Powell, Tim Goodman, Pat McCann, Arkell Farr, Dave Perrin, Gregg Law. Missing: Jeff Della Vedova.