1,712 research outputs found
Pulmonary imaging abnormalities in an adult case of congenital lobar emphysema.
Congenital lobar emphysema is mainly diagnosed in infants, although rare cases are reported in adults. A 20-yr-old female with acute dyspnea, chest pain and left upper lobe (LUL) chest x-ray hyperlucency underwent 3He magnetic resonance imaging (MRI) for ventilation and apparent diffusion coefficient (ADC) measurements, as well as CT for emphysema and airway wall measurements. Forced expiratory volume in 1s, residual volume, and airways-resistance were abnormal, but there was normal carbon-monoxide-diffusing-capacity. The LUL relative area of the density histogra
Combined tissue and fluid proteomics with Tandem Mass Tags to identify low-abundance protein biomarkers of disease in peripheral body fluid: An Alzheimer's Disease case study
RATIONALE:
Ideal biomarkers are present in readily accessible samples including plasma and cerebrospinal fluid (CSF), and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low-abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition mass spectrometry (MS). To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator™; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low-abundance, tissue-derived biomarkers.
METHODS:
A disease relevant cell line was labelled with TMT® in a range of concentrations generating a multi-point calibration curve. Peripheral biofluid samples were labelled with the remaining tags and quantitative analysis was performed using an Orbitrap Fusion Tribrid mass spectrometer with a Top10 CID-HCD MS3 synchronous precursor selection (SPS) method. SPS allowed direct analysis of non-depleted, unfractionated CSF samples with complete profiling of six individual samples requiring only 15 hours of MS time, equivalent to 1.5 h per sample.
RESULTS:
Using the TMTcalibrator™ workflow allowed the identification of several markers of microglia activation that are differentially quantified in the CSF of patients with Alzheimer's disease (AD). We report peptides from 41 proteins that have not previously been detected in the CSF, that appear to be regulated by at least 60% in AD.
CONCLUSIONS:
This study has demonstrated the benefits of the new TMTcalibrator™ workflow and the results suggest this is a suitable and efficient method of detecting low-abundance peptides within biological fluids. The use of TMTcalibrator™ in further biomarker discovery studies should be considered to overcome some of the limitations commonly associated with more conventional approaches
Anomalous anisotropic cross-correlations between WMAP CMB maps and SDSS galaxy distribution and implications on the dark flow scenario
We search for the dark flow induced diffuse kinetic Sunyaev Zel'dovich (kSZ)
effect through CMB-galaxy cross correlation. Such angular correlation is
anisotropic, with a unique angular dependence and hence can be
distinguished from other components. Here, is the angle between the
opposite dark flow direction and the direction of the sky where the correlation
is measured. We analyze the KIAS-VAGC galaxy catalog of SDSS-DR7 and the WMAP
seven-year temperature maps, applying an unbiased optimal weighting scheme to
eliminate any statistically isotropic components and to enhance the dark flow
detection signal. Non-zero weighted cross correlations are detected at 3.5
sigma for the redshift bin z<0.1 and at 3 sigma for the bin 0.1<z<0.2, implying
the existence of statistically anisotropic components in CMB. However, further
analysis does not support the dark flow explanation. The observed directional
dependence deviates from the relation expected, and
hence can not be explained by the presence of a single dark flow, and if the
observed cross correlation is generated by the dark flow induced kSZ effect,
the velocity would be too high (> 6000 km/s). We report this work as the first
attempt to search for dark flow through weighted CMB-galaxy cross correlation
and to draw the attention on the sources of the detected anomalous CMB-galaxy
cross correlation.Comment: 8 pages, 8 figures, ApJ accepte
A combined kinetico-mechanistic and computational study on the competitive formation of seven- versus five-membered platinacycles; the relevance of spectator halide ligands
The metalation reactions between [Pt2(4-MeC6H4)4(μ-SEt2)2] and 2-X,6-FC6H3CHvNCH2CH2NMe2 (X = Br, Cl) have been studied. In all cases, seven-membered platinacycles are formed in a process that involves an initial reductive elimination from cyclometallated PtIV intermediate compounds, [PtX(4-CH3C6H4)2(ArCHvNCH2CH2NMe2)] (X = Br, Cl), followed by isomerization of the resulting PtII complexes and a final cyclometallation step. For the process with X = Br, the final seven-membered platinacycle and two intermediates, isolated under the conditions implemented from parallel kinetic studies, have been characterized by XRD. Contrary to previous results for the parent non-fluorinated imine 2-BrC6H4CHvNCH2CH2NMe2 the presence of a fluoro substituent prevents the formation of the more stable five-membered platinacycle. Temperature and pressure dependent kinetico-mechanistic and DFT studies indicate that the final cyclometallation step is strongly influenced by the nature of the spectator halido ligand, the overall reaction being much faster for X = Cl. The same DFT study conducted on the previously studied systems with imine 2-BrC6H4CHvNCH2CH2NMe2 indicates that, when possible, fivemembered platinacycles are kinetically preferred for X = Br, while the presence of Cl as a spectator halido ligand leads to a preferential faster formation of seven-membered analogues
Associations between e-cigarette access and smoking and drinking behaviours in teenagers
Background: Public health concerns regarding e-cigarettes and debate on appropriate regulatory responses are
focusing on the need to prevent child access to these devices. However, little is currently known about the
characteristics of those young people that are accessing e-cigarettes.
Methods: Using a cross-sectional survey of 14-17 year old school students in North West England (n = 16,193) we
examined associations between e-cigarette access and demographics, conventional smoking behaviours, alcohol
consumption, and methods of accessing cigarettes and alcohol. Access to e-cigarettes was identified through a
question asking students if they had ever tried or purchased e-cigarettes.
Results: One in five participants reported having accessed e-cigarettes (19.2%). Prevalence was highest among\ud
smokers (rising to 75.8% in those smoking >5 per day), although 15.8% of teenagers that had accessed e-cigarettes
had never smoked conventional cigarettes (v.13.6% being ex-smokers). E-cigarette access was independently
associated with male gender, having parents/guardians that smoke and students’ alcohol use. Compared with
non-drinkers, teenagers that drank alcohol at least weekly and binge drank were more likely to have accessed
e-cigarettes (adjusted odds ratio [AOR] 1.89, P < 0.001), with this association particularly strong among never-smokers
(AOR 4.59, P < 0.001). Among drinkers, e-cigarette access was related to: drinking to get drunk, alcohol-related violence,
consumption of spirits; self-purchase of alcohol from shops or supermarkets; and accessing alcohol by recruiting adult
proxy purchasers outside shops.
Conclusions: There is an urgent need for controls on the promotion and sale of e-cigarettes to children. Findings
suggest that e-cigarettes are being accessed by teenagers more for experimentation than smoking cessation. Those
most likely to access e-cigarettes may already be familiar with illicit methods of accessing age-restricted substances
Molecular basis for the folding of β-helical autotransporter passenger domains
Bacterial autotransporters comprise a C-terminal β-barrel domain, which must be correctly folded and inserted into the outer membrane to facilitate translocation of the N-terminal passenger domain to the cell exterior. Once at the surface, the passenger domains of most autotransporters are folded into an elongated β-helix. In a cellular context, key molecules catalyze the assembly of the autotransporter β-barrel domain. However, how the passenger domain folds into its functional form is poorly understood. Here we use mutational analysis on the autotransporter Pet to show that the β-hairpin structure of the fifth extracellular loop of the β-barrel domain has a crucial role for passenger domain folding into a β-helix. Bioinformatics and structural analyses, and mutagenesis of a homologous autotransporter, suggest that this function is conserved among autotransporter proteins with β-helical passenger domains. We propose that the autotransporter β-barrel domain is a folding vector that nucleates folding of the passenger domain
A comparison of the galaxy peculiar velocity field with the PSCz gravity field-- A Bayesian hyper-parameter method
We constructed a Bayesian hyper-parameter statistical method to quantify the
difference between predicted velocities derived from the observed galaxy
distribution in the \textit{IRAS}-PSC redshift survey and peculiar
velocities measured using different distance indicators. In our analysis we
find that the model--data comparison becomes unreliable beyond 70 \hmpc
because of the inadequate sampling by \textit{IRAS} survey of prominent,
distant superclusters, like the Shapley Concentration. On the other hand, the
analysis of the velocity residuals show that the PSC gravity field provides
an adequate model to the local, \le 70 \hmpc, peculiar velocity field. The
hyper-parameter combination of ENEAR, SN, A1SN and SFI++ catalogues in the
Bayesian framework constrains the amplitude of the linear flow to be
. For an rms density fluctuations in the PSC galaxy
number density , we obtain an estimate of the
growth rate of density fluctuations ,
which is in excellent agreement with independent estimates based on different
techniques.Comment: 14 pages, 32 figures, MNRAS in press, matched the MNRAS published
versio
Measuring the cosmological bulk flow using the peculiar velocities of supernovae
We study large-scale coherent motion in our universe using the existing Type
IA supernovae data. If the recently observed bulk flow is real, then some
imprint must be left on supernovae motion. We run a series of Monte Carlo
Markov Chain runs in various redshift bins and find a sharp contrast between
the z 0.05 data. The$z < 0.05 data are consistent with the bulk
flow in the direction (l,b)=({290^{+39}_{-31}}^{\circ},
{20^{+32}_{-32}}^{\circ}) with a magnitude of v_bulk = 188^{+119}_{-103} km/s
at 68% confidence. The significance of detection (compared to the null
hypothesis) is 95%. In contrast, z > 0.05 data (which contains 425 of the 557
supernovae in the Union2 data set) show no evidence for bulk flow. While the
direction of the bulk flow agrees very well with previous studies, the
magnitude is significantly smaller. For example, the Kashlinsky, et al.'s
original bulk flow result of v_bulk > 600 km/s is inconsistent with our
analysis at greater than 99.7% confidence level. Furthermore, our best-fit bulk
flow velocity is consistent with the expectation for the \Lambda CDM model,
which lies inside the 68% confidence limit.Comment: Version published in JCA
The Vortex State in Geologic Materials: A Micromagnetic Perspective
A wide variety of Earth and planetary materials are very good recorders of paleomagnetic information. However most magnetic grains in these materials are not in the stable single (SD) domain grain size range, but are larger and in non-uniform vortex magnetization states. We provide a detailed account of vortex phenomena in geologic materials by simulating first-order reversal curves (FORCs) via finite-element micromagnetic modeling of magnetite nanoparticles with realistic morphologies. The particles have been reconstructed from focused ion beam nanotomography of magnetite-bearing obsidian, and accommodate single and multiple vortex structures. Single vortex (SV) grains have fingerprints with contributions to both the transient and transient-free zones of FORC diagrams. A fundamental feature of the SV fingerprint is a central ridge, representing a distribution of negative saturation vortex annihilation fields. SV irreversible events at multiple field values along different FORC branches determine the asymmetry in the upper and lower lobes of generic bulk FORC diagrams of natural materials with grains predominantly in the vortex state. Multi vortex (MV) FORC signatures are modeled here for the first time. MV grains contribute mostly to the transient-free zone of a FORC diagram, averaging out to create a broad central peak. The intensity of the central peak is higher than that of the lobes, implying that MV particles are more abundant than SV particles in geologic materials with vortex state fingerprints. The abundance of MV particles, as well as their SD-like properties point to MV grains being the main natural remanent magnetization carriers in geologic materials.European Research Counci
Distance in audio for VR: Constraints and opportunities
Spatial audio is enjoying a surge in attention in both scene and object based paradigms, due to the trend for, and accessibility of, immersive experience. This has been enabled through convergence in computing enhancements, component size reduction, and associated price reductions. For the first time, applications such as virtual reality (VR) are technologies for the consumer. Audio for VR is captured to provide a counterpart to the video or animated image, and can be rendered to combine elements of physical and psychoacoustic modelling, as well as artistic design. Given that distance is an inherent property of spatial audio, that it can augment sound's efficacy in cueing user attention (a problem which practitioners are seeking to solve), and that conventional film sound practices have intentionally exploited its use, the absence of research on its implementation and effects in immersive environments is notable. This paper sets out the case for its importance, from a perspective of research and practice. It focuses on cinematic VR, whose challenges for spatialized audio are clear, and at times stretches beyond the restrictions specific to distance in audio for VR, into more general audio constraints
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