236 research outputs found
Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end
Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process
Large Scale Structure of the Universe
Galaxies are not uniformly distributed in space. On large scales the Universe
displays coherent structure, with galaxies residing in groups and clusters on
scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of
galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space,
known as voids, contain very few galaxies and span the volume in between these
structures. This observed large scale structure depends both on cosmological
parameters and on the formation and evolution of galaxies. Using the two-point
correlation function, one can trace the dependence of large scale structure on
galaxy properties such as luminosity, color, stellar mass, and track its
evolution with redshift. Comparison of the observed galaxy clustering
signatures with dark matter simulations allows one to model and understand the
clustering of galaxies and their formation and evolution within their parent
dark matter halos. Clustering measurements can determine the parent dark matter
halo mass of a given galaxy population, connect observed galaxy populations at
different epochs, and constrain cosmological parameters and galaxy evolution
models. This chapter describes the methods used to measure the two-point
correlation function in both redshift and real space, presents the current
results of how the clustering amplitude depends on various galaxy properties,
and discusses quantitative measurements of the structures of voids and
filaments. The interpretation of these results with current theoretical models
is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets,
Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume
editor W. C. Keel, v2 includes additional references, updated to match
published versio
Testing in the incremental design and development of complex products
Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested
Fluids in cosmology
We review the role of fluids in cosmology by first introducing them in
General Relativity and then by applying them to a FRW Universe's model. We
describe how relativistic and non-relativistic components evolve in the
background dynamics. We also introduce scalar fields to show that they are able
to yield an inflationary dynamics at very early times (inflation) and late
times (quintessence). Then, we proceed to study the thermodynamical properties
of the fluids and, lastly, its perturbed kinematics. We make emphasis in the
constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book
"Computational and Experimental Fluid Mechanics with Applications to Physics,
Engineering and the Environment". Version 2: typos corrected and references
expande
Puzzle based teaching versus traditional instruction in electrocardiogram interpretation for medical students – a pilot study
<p>Abstract</p> <p>Background</p> <p>Most medical professionals are expected to possess basic electrocardiogram (EKG) interpretation skills. But, published data suggests that residents' and physicians' EKG interpretation skills are suboptimal. Learning styles differ among medical students; individualization of teaching methods has been shown to be viable and may result in improved learning. Puzzles have been shown to facilitate learning in a relaxed environment. The objective of this study was to assess efficacy of teaching puzzle in EKG interpretation skills among medical students.</p> <p>Methods</p> <p>This is a reader blinded crossover trial. Third year medical students from College of Human Medicine, Michigan State University participated in this study. Two groups (n = 9) received two traditional EKG interpretation skills lectures followed by a standardized exam and two extra sessions with the teaching puzzle and a different exam. Two other groups (n = 6) received identical courses and exams with the puzzle session first followed by the traditional teaching. EKG interpretation scores on final test were used as main outcome measure.</p> <p>Results</p> <p>The average score after only traditional teaching was 4.07 ± 2.08 while after only the puzzle session was 4.04 ± 2.36 (p = 0.97). The average improvement after the traditional session was followed up with a puzzle session was 2.53 ± 1.94 while the average improvement after the puzzle session was followed with the traditional session was 2.08 ± 1.73 (p = 0.67). The final EKG exam score for this cohort (n = 15) was 84.1 compared to 86.6 (p = 0.22) for a comparable sample of medical students (n = 15) at a different campus.</p> <p>Conclusion</p> <p>Teaching EKG interpretation with puzzles is comparable to traditional teaching and may be particularly useful for certain subgroups of students. Puzzle session are more interactive and relaxing, and warrant further investigations on larger scale.</p
New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range
We survey the phenomenological constraints on abelian gauge bosons having
masses in the MeV to multi-GeV mass range (using precision electroweak
measurements, neutrino-electron and neutrino-nucleon scattering, electron and
muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic
parity violation, low-energy neutron scattering and primordial
nucleosynthesis). We compute their implications for the three parameters that
in general describe the low-energy properties of such bosons: their mass and
their two possible types of dimensionless couplings (direct couplings to
ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue
that gauge bosons with very small couplings to ordinary fermions in this mass
range are natural in string compactifications and are likely to be generic in
theories for which the gravity scale is systematically smaller than the Planck
mass - such as in extra-dimensional models - because of the necessity to
suppress proton decay. Furthermore, because its couplings are weak, in the
low-energy theory relevant to experiments at and below TeV scales the charge
gauged by the new boson can appear to be broken, both by classical effects and
by anomalies. In particular, if the new gauge charge appears to be anomalous,
anomaly cancellation does not also require the introduction of new light
fermions in the low-energy theory. Furthermore, the charge can appear to be
conserved in the low-energy theory, despite the corresponding gauge boson
having a mass. Our results reduce to those of other authors in the special
cases where there is no kinetic mixing or there is no direct coupling to
ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which
appears in JHE
Psychometric evaluation of the Hospital Anxiety and Depression Scale in a large community sample of adolescents in Hong Kong
Purpose: The Hospital Anxiety and Depression Scale (HADS) is widely used in adult populations; however, its usefulness with adolescents has been explored less. This study sought to evaluate the reliability, validity, and factor structure of the Chinese version of HADS in a community sample of adolescents residing in Hong Kong. Methods: A prospective cohort of 5,857 students recruited from 17 secondary schools completed the HADS. Internal consistency and concurrent validity were examined. Confirmatory factor analysis was applied to test the relative fits of six factor structures of the HADS. The best fitting model was further cross-validated by male, female, splithalf samples, and age subgroups. Results: The HADS possessed adequate internal consistency, especially for the anxiety subscale. Significant concurrent intercorrelations with self-reported suicidal thoughts and the Youth Self Report Anxious/Depressed subscale were discovered and found to be stronger for females. The cross-validation supported a two-factor model, where anxiety item 7, "I can sit at ease and feel relaxed", was placed in the depression subscale. Conclusions: The HADS showed satisfactory psychometric properties as a screening instrument in assessing anxious and depressive states as two correlated but distinct factors in adolescents. Study implications and recommendations for future research were discussed.published_or_final_versionSpringer Open Choice, 21 Feb 201
The Confrontation between General Relativity and Experiment
The status of experimental tests of general relativity and of theoretical
frameworks for analysing them is reviewed. Einstein's equivalence principle
(EEP) is well supported by experiments such as the Eotvos experiment, tests of
special relativity, and the gravitational redshift experiment. Future tests of
EEP and of the inverse square law are searching for new interactions arising
from unification or quantum gravity. Tests of general relativity at the
post-Newtonian level have reached high precision, including the light
deflection, the Shapiro time delay, the perihelion advance of Mercury, and the
Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected
in an amount that agrees with general relativity to better than half a percent
using the Hulse-Taylor binary pulsar, and other binary pulsar systems have
yielded other tests, especially of strong-field effects. When direct
observation of gravitational radiation from astrophysical sources begins, new
tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article
originally published in 2001; final published version incorporating referees'
suggestion
Systemic Inhibition of NF-κB Activation Protects from Silicosis
Background: Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis. Methods/Findings: In the present work we evaluated the lung transplant database (May 1986-July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16-7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8-15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22-0.9 yr) following lung transplantation (2.4 yr; CI:1.5-3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica. Conclusions: Although limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis. © 2009 Di Giuseppe et al
Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterisation of soft biomaterials
Funding from the Engineering and Physical Sciences Research Council (EP/L505602/1) is gratefully acknowledged
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