93 resultados para endosome escape


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Stationary solutions to the equations of nonlinear diffusive shock acceleration play a fundamental role in the theory of cosmic-ray acceleration. Their existence usually requires that a fraction of the accelerated particles be allowed to escape from the system. Because the scattering mean free path is thought to be an increasing function of energy, this condition is conventionally implemented as an upper cutoff in energy space-particles are then permitted to escape from any part of the system, once their energy exceeds this limit. However, because accelerated particles are responsible for the substantial amplification of the ambient magnetic field in a region upstream of the shock front, we examine an alternative approach in which particles escape over a spatial boundary. We use a simple iterative scheme that constructs stationary numerical solutions to the coupled kinetic and hydrodynamic equations. For parameters appropriate for supernova remnants, we find stationary solutions with efficient acceleration when the escape boundary is placed at the point where growth and advection of strongly driven nonresonant waves are in balance. We also present the energy dependence of the distribution function close to the energy where it cuts off-a diagnostic that is in principle accessible to observation.

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The inherent difficulty of thread-based shared-memory programming has recently motivated research in high-level, task-parallel programming models. Recent advances of Task-Parallel models add implicit synchronization, where the system automatically detects and satisfies data dependencies among spawned tasks. However, dynamic dependence analysis incurs significant runtime overheads, because the runtime must track task resources and use this information to schedule tasks while avoiding conflicts and races.
We present SCOOP, a compiler that effectively integrates static and dynamic analysis in code generation. SCOOP combines context-sensitive points-to, control-flow, escape, and effect analyses to remove redundant dependence checks at runtime. Our static analysis can work in combination with existing dynamic analyses and task-parallel runtimes that use annotations to specify tasks and their memory footprints. We use our static dependence analysis to detect non-conflicting tasks and an existing dynamic analysis to handle the remaining dependencies. We evaluate the resulting hybrid dependence analysis on a set of task-parallel programs.

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Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s-1 and accelerated up to 7.5 m s-2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

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There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73: 51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single-or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 x 10(-6) per base per replication event. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

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Historically in Gaelic culture, the bard was greatly valued and admired as an important and integral part of society. Travelled, schooled and specifically trained in their art, the bard helped ensure identity and reassurance for Gaelic families by grounding them both temporarily and spatially into their landscape. Entrusted with the duty and responsibility of recording place and event, the bards worked without writing and by transgressing man-made boundaries, travelled throughout the land weaving their histories into the very fabric of society.

Now no longer with us, we find ourselves without the distinguished chronicler to undertake this duty. Yet the responsibility of the Gaelic bard is one still shared by all artists today; to facilitate memory and identity, whether good or bad. Many Ulster writers, by happenstance and geography have found themselves located in a place of painful histories. An immediate difficulty for those local writers becomes manifest by being intrinsically implicated into those histories – whilst having first-hand knowledge and comprehension beyond that of the outsider, the local writer is automatically damned by association and relationship, thereby tarnishing their voice in comparison to the perceived impartiality of others.
Some writers however have successfully sought ways to escape this limitation and have worked in ways that can transgress the restrictions of prejudgement. John Hewitt, by purposely becoming a self-imposed tourist was able to distance himself to write impartially about the past, recognising that ’the place without its ghosts is a barren place.’1 In ‘The Colony’,2 tradition, peoples and mapping of the land are all narrated by Hewitt in a similar way to the Gaelic bardic topographic poems of Sean O'Dubhagain and Giolla Na Naomh O'Huidhrin3 in compiling a rich cultural atlas.

Similarly the Belfast poet and novelist Ciaran Carson also writes and records the city from an intermediary position; that of translator. Mediating between reader and aisling,4 Carson himself takes the reader on a journey into name, meaning, time and place, focusing primarily on the city of Belfast, familiar in name but impenetrable in depth to most.

Furthermore, this once-forgotten tradition to chronicle is now being continued by the new breed of Irish crime writers where the likes of Brian McGilloway, Stuart Neville and Adrian McKinty can, by way of the crime novel, accurately record contemporary society. Thus, ghost estates, listed buildings, archaeological digs, street and city have all provided setting and subject matter for recent novels. Moreover by choosing the ‘outsider from within’ as their chief protagonist, whether detective or criminal, each author is able to transgress the boundaries of prejudice and preconception that hinder genuine understanding and knowledge.

Looking in turn at the Gaelic bard, the twentieth century Ulster poet and the new breed of Irish crime writer, the authors will outline the real value of the narrator, by being able to act as cultural transgressor beyond the seeming and alleged as the true chronicler in society, and then with specific reference to city and countryside in Ireland, as a valuable custodian of knowledge in architecture and place.

Keywords
Architecture, Crime Fiction, Cultural Atlas, Place, Poetry.

1 From ‘The Bloody Brae’, a one act play written by John Hewitt in the 1930’s.
2 Hewitt, J. (1968) published in Collected Poems 1932-67. London:McGibbon & Kee.
3 Lengthy and detailed medieval Gaelic poems composed in the fourteenth and fifteenth centuries first edited by John O'Donovan in 1862 for the Irish Archaeological and Celtic Society in Dublin.
4 The aisling is the Irish song or poem genre when the poet is visited by their muse in a daydream or dream-vision state.

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This article explores the construction of Andrea Dworkin as a public persona, or a ‘feminist icon’, revered by some and demonized by others. It argues that in both her fiction and non-fiction, Dworkin engaged in a process of writing herself as an exceptional woman, a ‘feminist militant’ as she describes herself in the subheading of her 2002 memoir, Heartbreak. The article illustrates Dworkin’s autobiographical logic of exceptionalism by comparing the story told in Heartbreak to the story of Dworkin’s major novel, Mercy, which features a heroine, Andrea, who shares Dworkin’s name and significant biographical details. While Dworkin has insisted that Mercy is not an autobiographical novel, the author undertakes a reading here of Mercy as the story of Dworkin if she had not become the feminist icon of her own and others’ construction. In Mercy, Andrea unsuccessfully attempts to escape the silent, victimized status that Dworkin has insistently argued is imposed upon women. In her repeated victimization, Andrea functions for Dworkin as an ‘everywoman’ who both embodies Dworkin’s world-view and highlights how Dworkin’s own biography exists in tension with some of her central assumptions about women, gender and contemporary society.

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Background

The prevalence, phenomenology aetiology and correlates of four forms of challenging behaviour in 32 children and adults with Smith-Magenis syndrome (SMS) were investigated.

Methods

Cognitive assessments, questionnaires and semi-structured interviews were used to gather data on intellectual disability, verbal and physical aggression, destructive behaviour and self-injury and on characteristics known to be associated with aggression.

Results

Aggression in SMS was more prevalent (87%), but not more severe than aggression in contrast groups. Aggressive behaviour was more frequently associated with environmental contingencies (e.g. attention, escape and access to tangibles) than self-injury and destructive behaviours. Severity of challenging behaviours was associated with high impulsivity.

Conclusion

Aggression is seen in the majority of people with SMS. Results suggest that behavioural disinhibition and operant social reinforcement are associated with the manifestation of aggression.

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Context. The VLT-FLAMES Tarantula Survey has an extensive view of the copious number of massive stars in the 30 Doradus (30 Dor) star forming region of the Large Magellanic Cloud. These stars play a crucial role in our understanding of the stellar feedback in more distant, unresolved star forming regions. Aims. The first comprehensive census of hot luminous stars in 30 Dor is compiled within a 10 arcmin (150 pc) radius of its central cluster, R136. We investigate the stellar content and spectroscopic completeness of the early type stars. Estimates were made for both the integrated ionising luminosity and stellar wind luminosity. These values were used to re-assess the star formation rate (SFR) of the region and determine the ionising photon escape fraction. Methods. Stars were selected photometrically and combined with the latest spectral classifications. Spectral types were estimated for stars lacking spectroscopy and corrections were made for binary systems, where possible. Stellar calibrations were applied to obtain their physical parameters and wind properties. Their integrated properties were then compared to global observations from ultraviolet (UV) to far-infrared (FIR) imaging as well as the population synthesis code, Starburst99. Results. Our census identified 1145 candidate hot luminous stars within 150 pc of R136 of which >700 were considered to be genuine early type stars and contribute to feedback. We assess the survey to be spectroscopically complete to 85% in the outer regions (>5 pc) but only 35% complete in the region of the R136 cluster, giving a total of 500 hot luminous stars in the census which had spectroscopy. Only 31 were found to be Wolf-Rayet (W-R) or Of/WN stars, but their contribution to the integrated ionising luminosity and wind luminosity was ~ 40% and ~ 50%, respectively. Similarly, stars with M > 100 M (mostly H-rich WN stars) also showed high contributions to the global feedback, ~ 25% in both cases. Such massive stars are not accounted for by the current Starburst99 code, which was found to underestimate the integrated ionising luminosity of R136 by a factor ~ 2 and the wind luminosity by a factor ~ 9. The census inferred a SFR for 30 Dor of 0.073 ± 0.04 M yr . This was generally higher than that obtained from some popular SFR calibrations but still showed good consistency with the far-UV luminosity tracer as well as the combined Hα and mid-infrared tracer, but only after correcting for Hα extinction. The global ionising output was also found to exceed that measured from the associated gas and dust, suggesting that ~6 % of the ionising photons escape the region. Conclusions. When studying the most luminous star forming regions, it is essential to include their most massive stars if one is to determine a reliable energy budget. Photon leakage becomes more likely after including their large contributions to the ionising output. If 30 Dor is typical of other massive star forming regions, estimates of the SFR will be underpredicted if this escape fraction is not accounted for.

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A low cost supercritical CO foaming rig with a novel design has been used to prepare fully interconnected and highly porous biodegradable scaffolds with controllable pore size and structure that can promote cancellous bone regeneration. Porous polymer scaffolds have been produced by plasticising the polymer with high pressure CO and by the formation of a porous structure following the escape of CO from the polymer. Although, control over pore size and structure has been previously reported as difficult with this process, the current study shows that control is possible. The effects of processing parameters such as CO saturation pressure, time and temperature and depressurisation rate on the morphological properties, namely porosity, pore interconnectivity, pore size and wall thickness- of the scaffolds have been investigated. Poly(d,l)lactic acid was used as the biodegradable polymer. The surfaces and internal morphologies of the poly(d,l)lactic acid scaffolds were examined using optical microscope and micro computed tomography. Preosteoblast human bone cells were seeded on the porous scaffolds in vitro to assess cell attachment and viability. The scaffolds showed a good support for cell attachment, and maintained cell viability throughout 7 days in culture. This study demonstrated that the morphology of the porous structure can be controlled by varying the foaming conditions, allowing the porous scaffolds to be used in various tissue engineering applications.

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Islands are contradictory places: they can be remote, mysterious spots, or lively centres of holiday revelry. They are associated alternately with escape, imprisonment, holiday and exile, and their exotic, otherworldly beauty has inspired artists and writers across the centuries. Islands have been sites of immense political, creative and scientific importance from Charles Darwin's enlightening voyage to the Gálapagos Islands, which resulted in his groundbreaking theory of evolution, to the moat-encased prisons incarcerating the world's most dangerous convicts.
Despite the common view of islands as earthly paradises, their often small size means they have restricted resources and limited opportunities for their inhabitants to thrive. In response, islanders have welcomed or sternly rejected, the fresh opportunities offered by turning their homes into tourist destinations. For people seeking beautiful landscapes, solitude or exciting adventure, islands are the most popular holiday spots in the world. They entice the rich and famous, and their allure has provided refuge and inspiration for artists and writers, from Paul Gauguin in Tahiti to George Orwell on Jura in the Hebrides, and general visitors alike.
Filled with illustrations, Islands is a comprehensive exploration of the geographical and cultural aspects of island life – their habitations and environments, their permanent residents and vast transitional populace, their colonial history and their enduring appeal to people around then world.

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Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.

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This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000 (TM), a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000 (TM) arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.

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This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.

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At the formation of the new Republic of Ireland, the construction of new infrastructures was seen as an essential element in the building of the new nation, just as the adoption of international style modernism in architecture was perceived as a way to escape the colonial past. Accordingly, infrastructure became the physical manifestation, the concrete identity of these objectives and architecture formed an integral part of this narrative. Moving between scales and from artefact to context, Infrastructure and the Architectures of Modernity in Ireland 1916-2016 provides critical insights and narratives on what is a complex and hitherto overlooked landscape, one which is often as much international as it is Irish. In doing so, it explores the interaction between the universalising and globalising tendencies of modernisation on one hand and the textures of local architectures on the other.

The book shows how the nature of technology and infrastructure is inherently cosmopolitan. Beginning with the building of the heroic Shannon hydro-electric facility at Ardnacrusha by the German firm of Siemens-Schuckert in the first decade of independence, Ireland became a point of varying types of intersection between imported international expertise and local need. Meanwhile, at the other end of the century, by the year 2000, Ireland had become one of the most globalized countries in the world, site of the European headquarters of multinationals such as Google and Microsoft. Climatically and economically expedient to the storing and harvesting of data, Ireland has subsequently become a repository of digital information farmed in large, single-storey sheds absorbed into anonymous suburbs. In 2013, it became the preferred site for Intel to design and develop its new microprocessor chip: the Galileo. The story of the decades in between, of shifts made manifest in architecture and infrastructure from the policies of economic protectionism, to the opening up of the country to direct foreign investment and the embracing of the EU, is one of the influx of technologies and cultural references into a small country on the edges of Europe as Ireland became both a launch-pad and testing ground for a series of aspects of designed modernity.