294 resultados para Martin, David


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Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related(1). These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae(2-5), closely related to the kelps(6,7) (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic(2) approaches to explore these and other(4,5) aspects of brown algal biology further.

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The work ROTATING BRAINS / BEATING HEART was specifically developed for the opening performance of the 2010 DRHA conference. The conference’s theme ‘Sensual Technologies: Collaborative Practices of Interdisciplinarity explored collaborative relationships between the body and sensual/sensing technologies across various disciplines, looking to new approaches offered by various emerging fields and practices that incorporate new and existing technologies. The conference had a specific focus on SecondLife with roundtable events and discussions, led by performance artist Stelarc, as well as international participation via SecondLife.
The collaboration between Stelarc, the Avatar Orchestra Metaverse (AOM) and myself as the DRHA2010 conference program chair was a unique occurrence for this conference.

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Purpose: Antiangiogenic therapies can be an important adjunct to the management of many malignancies. Here we investigated a novel protein, FKBPL, and peptide derivative for their antiangiogenic activity and mechanism of action.

Experimental Design: Recombinant FKBPL (rFKBPL) and its peptide derivative were assessed in a range of human microvascular endothelial cell (HMEC-1) assays in vitro. Their ability to inhibit proliferation, migration, and Matrigel-dependent tubule formation was determined. They were further evaluated in an ex vivo rat model of neovascularization and in two in vivo mouse models of angiogenesis, that is, the sponge implantation and the intravital microscopy models. Antitumor efficacy was determined in two human tumor xenograft models grown in severe compromised immunodeficient (SCID) mice. Finally, the dependence of peptide on CD44 was determined using a CD44-targeted siRNA approach or in cell lines of differing CD44 status.

Results: rFKBPL inhibited endothelial cell migration, tubule formation, and microvessel formation in vitro and in vivo. The region responsible for FKBPL's antiangiogenic activity was identified, and a 24-amino acid peptide (AD-01) spanning this sequence was synthesized. It was potently antiangiogenic and inhibited growth in two human tumor xenograft models (DU145 and MDA-231) when administered systemically, either on its own or in combination with docetaxel. The antiangiogenic activity of FKBPL and AD-01 was dependent on the cell-surface receptor CD44, and signaling downstream of this receptor promoted an antimigratory phenotype.

Conclusion: FKBPL and its peptide derivative AD-01 have potent antiangiogenic activity. Thus, these agents offer the potential of an attractive new approach to antiangiogenic therapy.

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Review essay on David Vann's Caribou Island

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The critical involvement of TGF-beta 1 (transforming growth factor-beta 1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-beta 1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-beta 1 and its physiological significance. CTGF was determined to bind directly to the T beta RIII (TGF-beta type III receptor) and antagonize TGF-beta 1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-beta 1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-beta 1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-beta 1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF Knockdown of T beta RIII restored TGF-beta 1-mediated Smad signalling and cell contractility, suggesting that T beta RIII is key for CTGF-mediated regulation of TGF-beta 1. Comparison of gene expression profiles from CTGF/TGF-beta 1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-beta 1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.

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We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.

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We present photometric and spectroscopic observations of a luminous Type IIP Supernova (SN) 2009kf discovered by the Pan-STARRS 1 (PS1) survey and also detected by the Galaxy Evolution Explorer. The SN shows a plateau in its optical and bolometric light curves, lasting approximately 70 days in the rest frame, with an absolute magnitude of M-V = - 18.4 mag. The P-Cygni profiles of hydrogen indicate expansion velocities of 9000 km s(-1) at 61 days after discovery which is extremely high for a Type IIP SN. SN 2009kf is also remarkably bright in the near-ultraviolet (NUV) and shows a slow evolution 10-20 days after optical discovery. The NUV and optical luminosity at these epochs can be modeled with a blackbody with a hot effective temperature (T similar to 16,000 K) and a large radius (R similar to 1 x 10(15) cm). The bright bolometric and NUV luminosity, the light curve peak and plateau duration, the high velocities, and temperatures suggest that 2009kf is a Type IIP SN powered by a larger than normal explosion energy. Recently discovered high-z SNe (0.7

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This article with the conception of space in Paul Celan's poetics, comparing it to Martin Buber's and developing a notion of 'realisation', important to both Celan and Buber. Partant du concept du fantastique en tant qu'espace dans laquelle les phénomènes sont véritablement perçus au lieu de simplement se dérouler, l'article montre comment la rupture avec la réalité accoutumée peut mener à une sensation intense de l'être. Chez Martin Buber se trouve la description d'un telle espace, où l'unité est créée à partir de la polarité de tout ce qui est. Le poème peut représenter un exemple d'un tel espace « réalisant ». La conception de l'espace chez Buber est démontrée en dialogue avec le poème STEHEN de Paul Celan, afin de montrer comment le monde réifié est « réalisé » par la poésie. Ainsi sont mis en valeur le rapport mutuel et le lien indispensable entre réalités sociales et la réalité du non-espace.

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Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent. SCZ (N=25) and BP (N=24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls. For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites. At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration.

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The growth of renewable power sources, distributed generation and the potential for alternative fuelled modes of transport such as electric vehicles has led to concerns over the ability of existing grid systems to facilitate such diverse portfolio mixes in already congested power systems. Internationally the growth in renewable energy sources is driven by government policy targets associated with the uncertainties of fossil fuel supplies, environmental issues and a move towards energy independence. Power grids were traditionally designed as vertically integrated centrally managed entities with fully dispatchable generating plant. Renewable power sources, distributed generation and alternative fuelled vehicles will place these power systems under additional stresses and strains due to their different operational characteristics. Energy storage and smart grid technologies are widely proposed as the tools to integrate these future diverse portfolio mixes within the more conventional power systems. The choice in these technologies is determined not only by their location on the grid system, but by the diversification in the power portfolio mix, the electricity market and the operational demands. This paper presents a high level technical and economic overview of the role and relevance of electrical energy storage and smart grid technologies in the next generation of renewable power systems.

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Interferometry has been used to investigate the spatio-temporal evolution of the electron number density in the initial stages of expansion following 248 nm ablation of a titanium target. Three-dimensional electron number densities are obtained from an interferogram of the plasma plume using the Abel inversion technique.