2,039 research outputs found
Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies
PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Calibration of myocardial T2 and T1 against iron concentration.
BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.
METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.
RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).
CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies
Strong Water Absorption in the Dayside Emission Spectrum of the Planet HD 189733b
Recent observations of the extrasolar planet HD 189733b did not reveal the
presence of water in the emission spectrum of the planet. Yet models of such
'Hot Jupiter' planets predict an abundance of atmospheric water vapour.
Validating and constraining these models is crucial for understanding the
physics and chemistry of planetary atmospheres in extreme environments.
Indications of the presence of water in the atmosphere of HD 189733b have
recently been found in transmission spectra, where the planet's atmosphere
selectively absorbs the light of the parent star, and in broadband photometry.
Here we report on the detection of strong water absorption in a high
signal-to-noise, mid-infrared emission spectrum of the planet itself. We find
both a strong downturn in the flux ratio below 10 microns and discrete spectral
features that are characteristic of strong absorption by water vapour. The
differences between these and previous observations are significant and admit
the possibility that predicted planetary-scale dynamical weather structures
might alter the emission spectrum over time. Models that match the observed
spectrum and the broadband photometry suggest that heat distribution from the
dayside to the night side is weak. Reconciling this with the high night side
temperature will require a better understanding of atmospheric circulation or
possible additional energy sources.Comment: 11 pages, 1 figure, published in Natur
Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.
Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth
Daily life stress and the cortisol awakening response : testing the anticipation hypothesis
Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD
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On the origin of utility, weighting, and discounting functions: How they get their shapes and how to change their shapes
We present a theoretical account of the origin of the shapes of utility, probability weighting, and temporal discounting functions. In an experimental test of the theory, we systematically change the shape of revealed utility, weighting, and discounting functions by manipulating the distribution of monies, probabilities, and delays in the choices used to elicit them. The data demonstrate that there is no stable mapping between attribute values and their subjective equivalents. Expected and discounted utility theories, and also their descendants such as prospect theory and hyperbolic discounting theory, simply assert stable mappings to describe choice data and offer no account of the instability we find. We explain where the shape of the mapping comes from and, in describing the mechanism by which people choose, explain why the shape depends on the distribution of gains, losses, risks, and delays in the environment
From weak coupling to spinning strings
We identify the gauge theory dual of a spinning string of minimal energy with
spins S_1, S_2 on AdS_5 and charge J on S^5. For this purpose we focus on a
certain set of local operators with two different types of covariant
derivatives acting on complex scalar fields. We analyse the corresponding
nested Bethe equations for the ground states in the limit of large spins. The
auxiliary Bethe roots form certain string configurations in the complex plane,
which enable us to derive integral equations for the leading and sub-leading
contribution to the anomalous dimension. The results can be expressed through
the observables of the sl(2) sub-sector, i.e. the cusp anomaly f(g) and the
virtual scaling function B_L(g), rendering the strong-coupling analysis
straightforward. Furthermore, we also study a particular sub-class of these
operators specialising to a scaling limit with finite values of the second spin
at weak and strong coupling.Comment: 23 pages, 3 figures, minor changes, references adde
Laterality and Flight: Concurrent Tests of Side-Bias and Optimality in Flying Tree Swallows
Behavioural side-bias occurs in many vertebrates, including birds as a result of hemispheric specialization and can be advantageous by improving response times to sudden stimuli and efficiency in multi-tasking. However, behavioural side-bias can lead to morphological asymmetries resulting in reduced performance for specific activities. For flying animals, wing asymmetry is particularly costly and it is unclear if behavioural side-biases will be expressed in flight; the benefits of quick response time afforded by side-biases must be balanced against the costs of less efficient flight due to the morphological asymmetry side-biases may incur. Thus, competing constraints could lead to context-dependent expression or suppression of side-bias in flight. In repeated flight trials through an outdoor tunnel with obstacles, tree swallows (Tachycineta bicolor) preferred larger openings, but we did not detect either individual or population-level side-biases. Thus, while observed behavioural side-biases during substrate-foraging and copulation are common in birds, we did not see such side-bias expressed in obstacle avoidance behaviour in flight. This finding highlights the importance of behavioural context for investigations of side-bias and hemispheric laterality and suggests both proximate and ultimate trade-offs between species-specific cognitive ecology and flight biomechanics
Controlling Cherenkov angles with resonance transition radiation
Cherenkov radiation provides a valuable way to identify high energy particles
in a wide momentum range, through the relation between the particle velocity
and the Cherenkov angle. However, since the Cherenkov angle depends only on
material's permittivity, the material unavoidably sets a fundamental limit to
the momentum coverage and sensitivity of Cherenkov detectors. For example, Ring
Imaging Cherenkov detectors must employ materials transparent to the frequency
of interest as well as possessing permittivities close to unity to identify
particles in the multi GeV range, and thus are often limited to large gas
chambers. It would be extremely important albeit challenging to lift this
fundamental limit and control Cherenkov angles as preferred. Here we propose a
new mechanism that uses constructive interference of resonance transition
radiation from photonic crystals to generate both forward and backward
Cherenkov radiation. This mechanism can control Cherenkov angles in a flexible
way with high sensitivity to any desired range of velocities. Photonic crystals
thus overcome the severe material limit for Cherenkov detectors, enabling the
use of transparent materials with arbitrary values of permittivity, and provide
a promising option suited for identification of particles at high energy with
enhanced sensitivity.Comment: There are 16 pages and 4 figures for the manuscript. Supplementary
information with 18 pages and 5 figures, appended at the end of the file with
the manuscript. Source files in Word format converted to PDF. Submitted to
Nature Physic
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