451 research outputs found
Assessing direct contributions of morphological awareness and prosodic sensitivity to children’s word reading and reading comprehension
We examined the independent contributions of prosodic sensitivity and morphological awareness to word reading, text reading accuracy, and reading comprehension. We did so in a longitudinal study of English-speaking children (N = 70). At 5 to 7 years of age, children completed the metalinguistic measures along with control measures of phonological awareness and vocabulary. Children completed the reading measures two years later. Morphological awareness, but not prosodic sensitivity made a significant independent contribution to word reading, text reading accuracy and reading comprehension. The effects of morphological awareness on reading comprehension remained after controls for word reading. These results suggest that morphological awareness needs to be considered seriously in models of reading development and that prosodic sensitivity might have primarily indirect relations to reading outcomes.
Keywords: Morphological Awareness; Prosody; Word Reading; Reading Comprehension
The Intermediate Filament Network in Cultured Human Keratinocytes Is Remarkably Extensible and Resilient
The prevailing model of the mechanical function of intermediate filaments in cells assumes that these 10 nm diameter filaments make up networks that behave as entropic gels, with individual intermediate filaments never experiencing direct loading in tension. However, recent work has shown that single intermediate filaments and bundles are remarkably extensible and elastic in vitro, and therefore well-suited to bearing tensional loads. Here we tested the hypothesis that the intermediate filament network in keratinocytes is extensible and elastic as predicted by the available in vitro data. To do this, we monitored the morphology of fluorescently-tagged intermediate filament networks in cultured human keratinocytes as they were subjected to uniaxial cell strains as high as 133%. We found that keratinocytes not only survived these high strains, but their intermediate filament networks sustained only minor damage at cell strains as high as 100%. Electron microscopy of stretched cells suggests that intermediate filaments are straightened at high cell strains, and therefore likely to be loaded in tension. Furthermore, the buckling behavior of intermediate filament bundles in cells after stretching is consistent with the emerging view that intermediate filaments are far less stiff than the two other major cytoskeletal components F-actin and microtubules. These insights into the mechanical behavior of keratinocytes and the cytokeratin network provide important baseline information for current attempts to understand the biophysical basis of genetic diseases caused by mutations in intermediate filament genes
The impact of labour regulations : measuring the effectiveness of legal norms in a developing country.
Gas isotope thermometry in the South Pole and Dome Fuji ice cores provides evidence for seasonal rectification of ice core gas records
Gas isotope thermometry using the isotopes of molecular nitrogen and argon
has been used extensively to reconstruct past surface temperature change
from Greenland ice cores. The gas isotope ratios δ15N and
δ40Ar in the ice core are each set by the amount of
gravitational and thermal fractionation in the firn. The gravitational
component of fractionation is proportional to the firn thickness, and the
thermal component is proportional to the temperature difference between the
top and bottom of the firn column, which can be related to surface
temperature change. Compared to Greenland, Antarctic climate change is
typically more gradual and smaller in magnitude, which results in smaller
thermal fractionation signals that are harder to detect. This has hampered
application of gas isotope thermometry to Antarctic ice cores.
Here, we present an analytical method for measuring δ15N and
δ40Ar with a precision of 0.002 ‰ per atomic
mass unit, a two-fold improvement on previous work. This allows us to
reconstruct changes in firn thickness and temperature difference at the South
Pole between 30 and 5 kyr BP. We find that variability in firn thickness is
controlled in part by changes in snow accumulation rate, which is, in turn,
influenced strongly by the along-flowline topography upstream of the ice
core site. Variability in our firn temperature difference record cannot be
explained by annual-mean processes. We therefore propose that the ice core
gas isotopes contain a seasonal bias due to rectification of seasonal
signals in the upper firn. The strength of the rectification also appears to
be linked to fluctuations in the upstream topography. As further evidence
for the existence of rectification, we present new data from the Dome Fuji
ice core that are also consistent with a seasonal bias throughout the
Holocene.
Our findings have important implications for the interpretation of ice core
gas records. For example, we show that the effects of upstream topography on
ice core records can be significant at flank sites like the South Pole – they
are responsible for some of the largest signals in our record. Presumably
upstream signals impact other flank-flow ice cores such as EDML, Vostok, and
EGRIP similarly. Additionally, future work is required to confirm the
existence of seasonal rectification in polar firn, to determine how spatially
and temporally widespread rectifier effects are, and to incorporate the
relevant physics into firn air models.</p
What's new pussycat? A genealogy of animal celebrity
Animal celebrity is a human creation informing us about our socially constructed natural world. It is relational, expressive of cultural proclivities, political power plays and the quotidian everyday, as well as serious philosophical reflections on the meaning of being human. This article attempts to outline some key contours in the genealogy of animal celebrity, showing how popular culture, including fairground attractions, public relations, Hollywood movies, documentary films, zoo attractions, commercial sport and mediatised moral panics - particularly those accompanying scientific developments such as cloning - help to order, categorise and license aspects of human understanding and feelings. The nature of [animal] charisma and celebrity are explored with assistance from Jumbo the Elephant, Guy the Gorilla, Paul the clairvoyant octopus, Uggie the film star, Nénette the orang-utan and Dolly the sheep. It argues that the issue of what it is to be human lies beneath the celebritised surface or, as Donna Haraway noted, the issue 'of having to face oneself'
Human Nail Plate Modifications Induced by Onychomycosis : Implications for Topical Therapy
Open Access - This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedConclusions: Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.Purpose: Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.Methods: The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake.Results: Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm3; diseased 1.29 ± 0.00 g/cm3). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle.Peer reviewe
Bureaucracy stifles medical research in Britain: a tale of three trials
<p>Abstract</p> <p>Background</p> <p>Recent developments aiming to standardise and streamline processes of gaining the necessary approvals to carry out research in the National Health Service (NHS) in the United Kingdom (UK), have resulted in lengthy and costly delays. The national UK governmental Department of Health’s Research Governance Framework (RGF) for Health and Social Care requires that appropriate checks be conducted before research involving human participants, their organs, tissues or data can commence in the NHS. As a result, medical research has been subjected to increased regulation and governance, with the requirement for approvals from numerous regulatory and monitoring bodies. In addition, the processes and outcomes of the attribution of costs in NHS research have caused additional difficulties for researchers. The purpose of this paper is to illustrate, through three trial case studies, the difficulties encountered during the set-up and recruitment phases of these trials, related to gaining the necessary ethical and governance approvals and applying for NHS costs to undertake and deliver the research.</p> <p>Methods</p> <p>Empirical evidence about delays and difficulties related to regulation and governance of medical research was gathered during the period 2009–2010 from three UK randomised controlled trials with sites in England, Wales and Scotland (1. SAFER 2- an emergency care based trial of a protocol for paramedics to refer patients directly to community based falls services; 2. COnStRUCT- a trial of two drugs for acute ulcerative colitis; and 3. Family Links - a trial of a public health intervention, a 10 week community based parenting programme). Findings and recommendations were reported in response to a call for evidence from The Academy of Medical Sciences regarding difficulties encountered in conducting medical research arising from R&D governance and regulation, to inform national policy.</p> <p>Results</p> <p>Difficulties and delays in navigating and gaining the appropriate approvals and NHS costs required to undertake the research were encountered in all three trials, at various points in the bureaucratic processes of ethical and research and information governance approvals. Conduct of each of the three trials was delayed by at least 12 months, with costs increasing by 30 – 40%.</p> <p>Conclusions</p> <p>Whilst the three trials encountered a variety of challenges, there were common issues. The processes for gaining approvals were overly complex and differed between sites and UK countries; guidance about processes was unclear; and information regarding how to define and claim NHS costs for undertaking the research was inconsistent. The competitive advantage of a publicly funded, open access health system for undertaking health services research and clinical trials within the UK has been outweighed in recent years by stifling bureaucratic structures and processes for governance of research. The recommendations of the Academy of Medical Sciences are welcomed, and the effects of their implementation are awaited with interest.</p> <p>Trial Registration numbers</p> <p>SAFER 2: ISRCTN 60481756; COnStRUCT: ISRCTN22663589; Family Links: ISRCTN 13929732</p
TMEFF2 Is a PDGF-AA Binding Protein with Methylation-Associated Gene Silencing in Multiple Cancer Types Including Glioma
BACKGROUND: TMEFF2 is a protein containing a single EGF-like domain and two follistatin-like modules. The biological function of TMEFF2 remains unclear with conflicting reports suggesting both a positive and a negative association between TMEFF2 expression and human cancers. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that the extracellular domain of TMEFF2 interacts with PDGF-AA. This interaction requires the amino terminal region of the extracellular domain containing the follistatin modules and cannot be mediated by the EGF-like domain alone. Furthermore, the extracellular domain of TMEFF2 interferes with PDGF-AA-stimulated fibroblast proliferation in a dose-dependent manner. TMEFF2 expression is downregulated in human brain cancers and is negatively correlated with PDGF-AA expression. Suppressed expression of TMEFF2 is associated with its hypermethylation in several human tumor types, including glioblastoma and cancers of ovarian, rectal, colon and lung origins. Analysis of glioma subtypes indicates that TMEFF2 hypermethylation and decreased expression are associated with a subset of non-Proneural gliomas that do not display CpG island methylator phentoype. CONCLUSIONS/SIGNIFICANCE: These data provide the first evidence that TMEFF2 can function to regulate PDGF signaling and that it is hypermethylated and downregulated in glioma and several other cancers, thereby suggesting an important role for this protein in the etiology of human cancers
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Variable relationship between accumulation and temperature in West Antarctica for the past 31,000 years
The Antarctic contribution to sea level is a balance between ice loss along the margin and accumulation in the interior. Accumulation records for the past few decades are noisy and show inconsistent relationships with temperature. We investigate the relationship between accumulation and temperature for the past 31 ka using high-resolution records from the West Antarctic Ice Sheet (WAIS) Divide ice core in West Antarctica. Although the glacial-interglacial increases result in high correlation and moderate sensitivity for the full record, the relationship shows considerable variability through time with high correlation and high sensitivity for the 0–8 ka period but no correlation for the 8–15 ka period. This contrasts with a general circulation model simulation which shows homogeneous sensitivities between temperature and accumulation across the entire time period. These results suggest that variations in atmospheric circulation are an important driver of Antarctic accumulation but they are not adequately captured in model simulations. Model-based projections of future Antarctic accumulation, and its impact on sea level, should be treated with caution
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