5,534 research outputs found
X-ray diffraction from bone employing annular and semi-annular beams
This is the final version of the article. Available from the publisher via the DOI in this record.There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.We acknowledge gratefully the funding provided by the UK Engineering and Physical
Sciences Research Council (EPSRC) grant number EP/K020196/
Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ.
Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-β (ESRRβ), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRβ (MHC-ERRB KO) develop DCM and sudden death at ~10 mo of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM but not other forms of cardiomyopathy (ischemic, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRβ is a critical component in the onset of DCM by affecting contractility and calcium balance.NEW & NOTEWORTHY Estrogen-related receptor-β (ESRRβ) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRβ is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRβ in the pathogenesis of DCM in humans
Guanine and 7,8-dihydro-8-oxo-guanine-specific oxidation in DNA by chromium(V).
The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate the lesions generated from this oxidation process. Reaction of Cr(V)-Salen with synthetic oligonucleotides produced guanine-specific lesions that were not 8-oxo-2'-deoxyguanosine, based on the inability of iridium(IV) to further oxidize these sites. Oxidation products were identified using a 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-G) containing oligonucleotide to increase the yields of product for identification by electrospray ionization mass spectrometry. The guanine-based lesions observed by mass spectrometry corresponded to the lesions guanidinohydantoin and spiroiminodihydantoin. The effects of these Cr(V)-Salen-induced lesions on DNA replication fidelity was assayed using a polymerase-based misincorporation assay. These lesions produced G --> T transversion mutations and polymerase stops at levels greater than those observed for 8-oxo-G. These data suggest a model by which chromate can cause DNA damage leading to mutations and cancer
Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels
The hair cell's mechanoreceptive organelle, the hair bundle, is highly
sensitive because its transduction channels open over a very narrow range of
displacements. The synchronous gating of transduction channels also underlies
the active hair-bundle motility that amplifies and tunes responsiveness. The
extent to which the gating of independent transduction channels is coordinated
depends on how tightly individual stereocilia are constrained to move as a
unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that
thermal movements of stereocilia located as far apart as a bundle's opposite
edges display high coherence and negligible phase lag. Because the mechanical
degrees of freedom of stereocilia are strongly constrained, a force applied
anywhere in the hair bundle deflects the structure as a unit. This feature
assures the concerted gating of transduction channels that maximizes the
sensitivity of mechanoelectrical transduction and enhances the hair bundle's
capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200
Helicity at Photospheric and Chromospheric Heights
In the solar atmosphere the twist parameter has the same sign as
magnetic helicity. It has been observed using photospheric vector magnetograms
that negative/positive helicity is dominant in the northern/southern hemisphere
of the Sun. Chromospheric features show dextral/sinistral dominance in the
northern/southern hemisphere and sigmoids observed in X-rays also have a
dominant sense of reverse-S/forward-S in the northern/southern hemisphere. It
is of interest whether individual features have one-to-one correspondence in
terms of helicity at different atmospheric heights. We use UBF \Halpha images
from the Dunn Solar Telescope (DST) and other \Halpha data from Udaipur Solar
Observatory and Big Bear Solar Observatory. Near-simultaneous vector
magnetograms from the DST are used to establish one-to-one correspondence of
helicity at photospheric and chromospheric heights. We plan to extend this
investigation with more data including coronal intensities.Comment: 5 pages, 1 figure, 1 table To appear in "Magnetic Coupling between
the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten,
Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg,
Berlin, 200
3D multi-agent models for protein release from PLGA spherical particles with complex inner morphologies
In order to better understand and predict the release of proteins from bioerodible micro- or nanospheres, it is important to know the influences of different initial factors on the release mechanisms. Often though it is difficult to assess what exactly is at the origin of a certain dissolution profile. We propose here a new class of fine-grained multi-agent models built to incorporate
increasing complexity, permitting the exploration of the role of different parameters, especially that of the internal morphology of the spheres, in the exhibited release profile. This approach, based on Monte-Carlo (MC) and Cellular Automata (CA) techniques, has permitted the testing of various assumptions and hypotheses about several experimental systems of nanospheres encapsulating proteins. Results have confirmed that this modelling approach
has increased the resolution over the complexity involved, opening promising perspectives for future developments, especially complementing in vitro experimentation
Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale
The detection of sound begins when energy derived from acoustic stimuli
deflects the hair bundles atop hair cells. As hair bundles move, the viscous
friction between stereocilia and the surrounding liquid poses a fundamental
challenge to the ear's high sensitivity and sharp frequency selectivity. Part
of the solution to this problem lies in the active process that uses energy for
frequency-selective sound amplification. Here we demonstrate that a
complementary part involves the fluid-structure interaction between the liquid
within the hair bundle and the stereocilia. Using force measurement on a
dynamically scaled model, finite-element analysis, analytical estimation of
hydrodynamic forces, stochastic simulation and high-resolution interferometric
measurement of hair bundles, we characterize the origin and magnitude of the
forces between individual stereocilia during small hair-bundle deflections. We
find that the close apposition of stereocilia effectively immobilizes the
liquid between them, which reduces the drag and suppresses the relative
squeezing but not the sliding mode of stereociliary motion. The obliquely
oriented tip links couple the mechanotransduction channels to this least
dissipative coherent mode, whereas the elastic horizontal top connectors
stabilize the structure, further reducing the drag. As measured from the
distortion products associated with channel gating at physiological stimulation
amplitudes of tens of nanometres, the balance of forces in a hair bundle
permits a relative mode of motion between adjacent stereocilia that encompasses
only a fraction of a nanometre. A combination of high-resolution experiments
and detailed numerical modelling of fluid-structure interactions reveals the
physical principles behind the basic structural features of hair bundles and
shows quantitatively how these organelles are adapted to the needs of sensitive
mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please
see the online version of the article at http://www.nature.com/natur
Spin and Statistics and First Principles
It was shown in the early Seventies that, in Local Quantum Theory (that is
the most general formulation of Quantum Field Theory, if we leave out only the
unknown scenario of Quantum Gravity) the notion of Statistics can be grounded
solely on the local observable quantities (without assuming neither the
commutation relations nor even the existence of unobservable charged field
operators); one finds that only the well known (para)statistics of Bose/Fermi
type are allowed by the key principle of local commutativity of observables. In
this frame it was possible to formulate and prove the Spin and Statistics
Theorem purely on the basis of First Principles.
In a subsequent stage it has been possible to prove the existence of a
unique, canonical algebra of local field operators obeying ordinary Bose/Fermi
commutation relations at spacelike separations. In this general guise the Spin
- Statistics Theorem applies to Theories (on the four dimensional Minkowski
space) where only massive particles with finite mass degeneracy can occur. Here
we describe the underlying simple basic ideas, and briefly mention the
subsequent generalisations; eventually we comment on the possible validity of
the Spin - Statistics Theorem in presence of massless particles, or of
violations of locality as expected in Quantum Gravity.Comment: Survey based on a talk given at the Meeting on "Theoretical and
experimental aspects of the spin - statistics connection and related
symmetries", Trieste, Italy - October 21-25, 200
Energy-dispersive X-ray diffraction using an annular beam
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We demonstrate material phase identification by measuring polychromatic diffraction spots from samples at least 20 mm in diameter and up to 10 mm thick with an energy resolving point detector. Within our method an annular X-ray beam in the form of a conical shell is incident with its symmetry axis normal to an extended polycrystalline sample. The detector is configured to receive diffracted flux transmitted through the sample and is positioned on the symmetry axis of the annular beam. We present the experiment data from a range of different materials and demonstrate the acquisition of useful data with sub-second collection times of 0.5 s; equating to 0.15 mAs. Our technique should be highly relevant in fields that demand rapid analytical methods such as medicine, security screening and non-destructive testing.We acknowledge gratefully the funding provided by the UK Engineering and Physical
Sciences Research Council (EPSRC) grant number EP/K020196/1
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