Ethics, Gesture and the Western

This paper relates the Western Movie to Agamben’s implied gestural zone between intention and act. Film is important in the realisation of this zone because it was the first means of representation to capture the body in movement. The Western movie explores the space of ethical indistinction between the acts of individual fighters and the establishment of a rule of law, or putting this another way, between violence and justice. Two classic examples of an archetypal Western plot (Shane, 1953 and Unforgiven, 1991) that particularly embodies this are cited. In both a gunfighter who has forsworn violence at the start is led by the circumstances of the plot to take it up once more at the conclusion. In these terms all the gestures contained between these beginning- and end-points are analysable as an ethics of gesture because, captured as gestures, they occupy the human space between abstraction and action, suspended between them, and reducible to neither.  David Foster Wallace's definition of this narrative arc in Infinite Jest (and embodied in it) is adduced in order to suggest a parallel between Agamben's notion of an ethics of gesture, and an ethics of genre

Experimental salt marsh islands: a model system for novel metacommunity experiments

Shallow tidal coasts are characterised by shifting tidal flats and emerging or eroding islands above the high tide line. Salt marsh vegetation colonising new habitats distant from existing marshes are an ideal model to investigate metacommunity theory. We installed a set of 12 experimental salt marsh islands made from metal cages on a tidal flat in the German Wadden Sea to study the assembly of salt marsh communities in a metacommunity context. Experimental plots at the same elevation were established within the adjacent salt marsh on the island of Spiekeroog. For both, experimental islands and salt marsh enclosed plots, the same three elevational levels were realised while creating bare patches open for colonisation and vegetated patches with a defined transplanted community. One year into the experiment, the bare islands were colonised by plant species with high fecundity although with a lower frequency compared to the salt marsh enclosed bare plots. Initial plant community variations due to species sorting along the inundation gradient were evident in the transplanted vegetation. Competitive exclusion was not observed and is only expected to unfold in the coming years. Our study highlights that spatially and temporally explicit metacommunity dynamics should be considered in salt marsh plant community assembly and disassembly

Lyl1 interacts with CREB1 and alters expression of CREB1 target genes

AbstractThe basic helix-loop-helix (bHLH) transcription factor family contains key regulators of cellular proliferation and differentiation as well as the suspected oncoproteins Tal1 and Lyl1. Tal1 and Lyl1 are aberrantly over-expressed in leukemia as a result of chromosomal translocations, or other genetic or epigenetic events. Protein-protein and protein-DNA interactions described so far are mediated by their highly homologous bHLH domains, while little is known about the function of other protein domains. Hetero-dimers of Tal1 and Lyl1 with E2A or HEB, decrease the rate of E2A or HEB homo-dimer formation and are poor activators of transcription. In vitro, these hetero-dimers also recognize different binding sites from homo-dimer complexes, which may also lead to inappropriate activation or repression of promoters in vivo. Both mechanisms are thought to contribute to the oncogenic potential of Tal1 and Lyl1. Despite their bHLH structural similarity, accumulating evidence suggests that Tal1 and Lyl1 target different genes. This raises the possibility that domains flanking the bHLH region, which are distinct in the two proteins, may participate in target recognition. Here we report that CREB1, a widely-expressed transcription factor and a suspected oncogene in acute myelogenous leukemia (AML) was identified as a binding partner for Lyl1 but not for Tal1. The interaction between Lyl1 and CREB1 involves the N terminal domain of Lyl1 and the Q2 and KID domains of CREB1. The histone acetyl-transferases p300 and CBP are recruited to these complexes in the absence of CREB1 Ser 133 phosphorylation. In the Id1 promoter, Lyl1 complexes direct transcriptional activation. We also found that in addition to Id1, over-expressed Lyl1 can activate other CREB1 target promoters such as Id3, cyclin D3, Brca1, Btg2 and Egr1. Moreover, approximately 50% of all gene promoters identified by ChIP-chip experiments were jointly occupied by CREB1 and Lyl1, further strengthening the association of Lyl1 with Cre binding sites. Given the newly recognized importance of CREB1 in AML, the ability of Lyl1 to modulate promoter responses to CREB1 suggests that it plays a role in the malignant phenotype by occupying different promoters than Tal1

Tumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase.

Tumor necrosis factor alpha (TNF alpha) has multiple biological functions including the prolonged activation of the collagenase and c-jun genes, which are regulated via their AP-1 binding sites. We show that incubating human fibroblasts with TNF alpha induces prolonged activation of JNK, the c-Jun kinase, which phosphorylates the transactivation domain of c-Jun. Furthermore, an immune complex kinase assay specifically demonstrates that TNF alpha stimulates the activity of JNK1, the recently described predominant form of JNK. TNF alpha also produces a small and transient increase in extracellular signal-regulated kinase (ERK) activity and no measured increase in Raf-1 kinase activity. On the other hand, epidermal growth factor causes a prolonged activation of Raf-1 kinase and ERK activity and a smaller, more transient activation of JNK, whereas the phorbol ester phorbol 12-myristate 13-acetate causes a small stimulation of Raf-1 kinase and a pronounced stimulation of ERK activity. The activation of JNK by TNF alpha does not correlate with Raf-1 or ERK activity. The kinetics of Raf-1, ERK, and JNK induction by epidermal growth factor, phorbol 12-myristate 13-acetate, or TNF alpha indicate distinct mechanisms of activation in human fibroblasts

Measurements and Analysis of Secondary User Device Effects on Digital Television Receivers

This is the published version. Copyright © 2009 Newman et al.This article presents results from a study of the potential effects of secondary users operating in unoccupied television spectrum. Television spectrum is known within the wireless communications community as being underutilized, making it a prime candidate for dynamic spectrum access. The proposed use of this open spectrum has prompted questions concerning the quantity of available channel space that could be used without negative impact on consumers who view digital television broadcasts and the viability of secondary use of open channels immediately adjacent to a digital television broadcast channel. In this work, we investigate secondary device operation in the channels directly adjacent to a desired television channel, and the effects upon a selection of consumer digital television (DTV) receivers. Our observations strongly suggest that secondary users could operate "White Space Devices" (WSDs) in unoccupied channel bandwidth directly adjacent to a desired digital television (DTV) channel, with no observable adverse impact upon the reception of the desired channel content

Inducible fluorescent speckle microscopy

The understanding of cytoskeleton dynamics has benefited from the capacity to generate fluorescent fiducial marks on cytoskeleton components. Here we show that light-induced imprinting of three-dimensional (3D) fluorescent speckles significantly improves speckle signal and contrast relative to classic (random) fluorescent speckle microscopy. We predict theoretically that speckle imprinting using photobleaching is optimal when the laser energy and fluorophore responsivity are related by the golden ratio. This relation, which we confirm experimentally, translates into a 40% remaining signal after speckle imprinting and provides a rule of thumb in selecting the laser power required to optimally prepare the sample for imaging. This inducible speckle imaging (ISI) technique allows 3D speckle microscopy to be performed in readily available libraries of cell lines or primary tissues expressing fluorescent proteins and does not preclude conventional imaging before speckle imaging. As a proof of concept, we use ISI to measure metaphase spindle microtubule poleward flux in primary cells and explore a scaling relation connecting microtubule flux to metaphase duration.H. Maiato is funded by the seventh framework program grant PRE CISE from the European Research Council, FLAD Life Science 2020, and the Louis-Jeantet Young Investigator Career Award

Therapeutic approaches to pediatric COVID-19: an online survey of pediatric rheumatologists

Data on therapy of COVID-19 in immunocompetent and immunosuppressed children are scarce. We aimed to explore management strategies of pediatric rheumatologists. All subscribers to international Pediatric Rheumatology Bulletin Board were invited to take part in an online survey on therapeutic approaches to COVID-19 in healthy children and children with autoimmune/inflammatory diseases (AID). Off-label therapies would be considered by 90.3% of the 93 participating respondents. In stable patients with COVID-19 on oxygen supply (stage I), use of remdesivir (48.3%), azithromycin (26.6%), oral corticosteroids (25.4%) and/or hydroxychloroquine (21.9%) would be recommended. In case of early signs of 'cytokine storm' (stage II) or in critically ill patients (stage III) (a) anakinra (79.5% stage II; 83.6% stage III) or tocilizumab (58.0% and 87.0%, respectively); (b) corticosteroids (oral 67.2% stage II, intravenously 81.7% stage III); (c) intravenous immunoglobulins (both stages 56.5%); or (d) remdesivir (both stages 46.7%) were considered. In AID, > 94.2% of the respondents would not support a preventive adaptation of the immunomodulating therapy. In case of mild COVID-19, more than 50% of the respondents would continue pre-existing treatment with immunoglobulins (100%), hydroxychloroquine (94.2%), anakinra (79.2%) or canakinumab (72.5%), or tocilizumab (69.8%). Long-term corticosteroids would be reduced by 26.9% (< = 2 mg/kg/d) and 50.0% (> 2 mg/kg/day), respectively, with only 5.8% of respondents voting to discontinue the therapy. Conversely, more than 75% of respondents would refrain from administering cyclophosphamide and anti-CD20-antibodies. As evidence on management of pediatric COVID-19 is incomplete, continuous and critical expert opinion and knowledge exchange is helpful

Policy challenges for the pediatric rheumatology workforce: Part I. Education and economics

For children with rheumatic conditions, the available pediatric rheumatology workforce mitigates their access to care. While the subspecialty experiences steady growth, a critical workforce shortage constrains access. This three-part review proposes both national and international interim policy solutions for the multiple causes of the existing unacceptable shortfall. Part I explores the impact of current educational deficits and economic obstacles which constrain appropriate access to care. Proposed policy solutions follow each identified barrier