212 research outputs found
Comprehensive determination of the high-pressure structural behaviour of BaTiO<sub>3</sub>
We have mapped the phase diagram of BaTiO3 more extensively than previous attempts using high-pressure neutron-powder diffraction. The mapping of the phase diagram has been performed using isothermal compression at fixed temperatures (175, 225, 290, 480 K) within each of the known crystallographic phases, up to βΌ6 GPa using a large volume press. The crystallographic structure of each phase has been measured, and the determined absolute atomic displacements of all atoms within the cell have provided detailed information on the order of the phase transitions observed, and the behaviour of the ferroelectric dipole moment.Publisher PDFPeer reviewe
Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice
Little is known of the environmental factors that initiate and promote disease. The aryl hydrocarbon receptor (AHR) is a key regulator of xenobiotic metabolism and plays a major role in gene/environment interactions. The AHR has also been demonstrated to carry out critical functions in development and disease. A qualitative investigation into the contribution by the AHR when stimulated to different levels of activity was undertaken to determine whether AHR-regulated gene/environment interactions are an underlying cause of cardiovascular disease. We used two congenic mouse models differing at the Ahr gene, which encodes AHRs with a 10-fold difference in signaling potencies. Benzo[a]pyrene (BaP), a pervasive environmental toxicant, atherogen, and potent agonist for the AHR, was used as the environmental agent for AHR activation. We tested the hypothesis that activation of the AHR of different signaling potencies by BaP would have differential effects on the physiology and pathology of the mouse cardiovascular system. We found that differential AHR signaling from an exposure to BaP caused lethality in mice with the low-affinity AHR, altered the growth rates of the body and several organs, induced atherosclerosis to a greater extent in mice with the high-affinity AHR, and had a huge impact on gene expression of the aorta. Our studies also demonstrated an endogenous role for AHR signaling in regulating heart size. We report a gene/environment interaction linking differential AHR signaling in the mouse to altered aorta gene expression profiles, changes in body and organ growth rates, and atherosclerosis
βOff With Their Headsβ: British Prime Ministers and the Power to Dismiss
The British prime ministerβs power to appoint and dismiss ministers is probably his most important single power. This article explores how prime ministers from Macmillan to Blair have used that power. The article considers the criteria that prime ministers use when choosing to appoint or dismiss individuals from office before examining the calculations and miscalculations that prime ministers have made in practice. Finally, the article analyses the way that prime ministers have exercised, in particular, their power to dismiss and finds that Thatcher was far more likely than others to sack cabinet colleagues on ideological or policy grounds. The article emphasizes that prime ministersβ relationships with especially powerful ministers β βbig beasts of the jungleβ β are crucial to an understanding of British government at the top.</jats:p
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Low-intermediate-temperature, high-pressure thermoelastic and crystallographic properties of thermoelectric clausthalite (PbSe-I)
The thermoelastic properties of the rock-salt structured thermoelectric lead selenide
(clausthalite, PbSe-I) have been determined using neutron powder diffraction techniques for
the temperature interval 10 - 500 K at ambient pressure, and 0 - 5.2 GPa at 298, and 150 K.
Within this temperature range, lead selenide can be described using the same selfconsistent
phenomenological model developed for the isostructural phases lead sulfide
(PbS) and lead telluride (PbTe) in which the cations and anions behave as independent
Debye oscillators (vibrational Debye temperatures of PbSe-I: Pb 111(1) K, Se 205(1) K).
Simultaneous fitting of the unit cell volume and isochoric heat capacity to a two-term Debye
internal energy function gives characteristic temperatures of 104(3) K and 219(5) K in
excellent agreement with the two vibrational Debye temperatures derived from fitting the
individual atomic displacement parameters. GrΓΌneisen constants for the two term fits are
1.79 and 2.28 for the lower and upper characteristic temperature respectively. The
calculated thermodynamic GrΓΌneisen parameter increases monotonically from 2.03 at 10 K,
to a maximum 2.22 at 100 K before decreasing back to 2.00 at 298 K and is broadly in
agreement with the average of the two GrΓΌneisen parameters associated with the two-term
internal energy function. Despite the simplicity of the model, the calculated phonon density of
states that is implicit within the two-term Debye model is found to show fair agreement with
the full and partial vibrational densities of states derived from density functional theory
(DFT). The bulk modulus and its pressure derivative at 298 K are 47.9(4) GPa and 5.4(2)
respectively by fitting the pressure dependence of the unit cell volume to a 3rd order Birch-
Murnaghan equation-of-state. For lower temperatures (T < 300 K) the high-pressure
transition to PbSe-II is associated with a steep initial Clapeyron slope of 151 K GPa-1
Recovering local structure information from highβpressure total scattering experiments
High pressure is a powerful thermodynamic tool for exploring the structure and the phase behaviour of the crystalline state, and is now widely used in conventional crystallographic measurements. Highβpressure local structure measurements using neutron diffraction have, thus far, been limited by the presence of a strongly scattering, perdeuterated, pressureβtransmitting medium (PTM), the signal from which contaminates the resulting pair distribution functions (PDFs). Here, a method is reported for subtracting the pairwise correlations of the commonly used 4:1 methanol:ethanol PTM from neutron PDFs obtained under hydrostatic compression. The method applies a molecularβdynamicsβinformed empirical correction and a nonβnegative matrix factorization algorithm to recover the PDF of the pure sample. Proof of principle is demonstrated, producing corrected highβpressure PDFs of simple crystalline materials, Ni and MgO, and benchmarking these against simulated data from the average structure. Finally, the first local structure determination of Ξ±βquartz under hydrostatic pressure is presented, extracting compression behaviour of the realβspace structure
Optimization of Cell Morphology Measurement via Single-Molecule Tracking PALM
In neurons, the shape of dendritic spines relates to synapse function, which is rapidly altered during experience-dependent neural plasticity. The small size of spines makes detailed measurement of their morphology in living cells best suited to super-resolution imaging techniques. The distribution of molecular positions mapped via live-cell Photoactivated Localization Microscopy (PALM) is a powerful approach, but molecular motion complicates this analysis and can degrade overall resolution of the morphological reconstruction. Nevertheless, the motion is of additional interest because tracking single molecules provides diffusion coefficients, bound fraction, and other key functional parameters. We used Monte Carlo simulations to examine features of single-molecule tracking of practical utility for the simultaneous determination of cell morphology. We find that the accuracy of determining both distance and angle of motion depend heavily on the precision with which molecules are localized. Strikingly, diffusion within a bounded region resulted in an inward bias of localizations away from the edges, inaccurately reflecting the region structure. This inward bias additionally resulted in a counterintuitive reduction of measured diffusion coefficient for fast-moving molecules; this effect was accentuated by the long camera exposures typically used in single-molecule tracking. Thus, accurate determination of cell morphology from rapidly moving molecules requires the use of short integration times within each image to minimize artifacts caused by motion during image acquisition. Sequential imaging of neuronal processes using excitation pulses of either 2 ms or 10 ms within imaging frames confirmed this: processes appeared erroneously thinner when imaged using the longer excitation pulse. Using this pulsed excitation approach, we show that PALM can be used to image spine and spine neck morphology in living neurons. These results clarify a number of issues involved in interpretation of single-molecule data in living cells and provide a method to minimize artifacts in single-molecule experiments
An Integrated Strategy to Study Muscle Development and Myofilament Structure in Caenorhabditis elegans
A crucial step in the development of muscle cells in all metazoan animals is the assembly and anchorage of the sarcomere, the essential repeat unit responsible for muscle contraction. In Caenorhabditis elegans, many of the critical proteins involved in this process have been uncovered through mutational screens focusing on uncoordinated movement and embryonic arrest phenotypes. We propose that additional sarcomeric proteins exist for which there is a less severe, or entirely different, mutant phenotype produced in their absence. We have used Serial Analysis of Gene Expression (SAGE) to generate a comprehensive profile of late embryonic muscle gene expression. We generated two replicate long SAGE libraries for sorted embryonic muscle cells, identifying 7,974 protein-coding genes. A refined list of 3,577 genes expressed in muscle cells was compiled from the overlap between our SAGE data and available microarray data. Using the genes in our refined list, we have performed two separate RNA interference (RNAi) screens to identify novel genes that play a role in sarcomere assembly and/or maintenance in either embryonic or adult muscle. To identify muscle defects in embryos, we screened specifically for the Pat embryonic arrest phenotype. To visualize muscle defects in adult animals, we fed dsRNA to worms producing a GFP-tagged myosin protein, thus allowing us to analyze their myofilament organization under gene knockdown conditions using fluorescence microscopy. By eliminating or severely reducing the expression of 3,300 genes using RNAi, we identified 122 genes necessary for proper myofilament organization, 108 of which are genes without a previously characterized role in muscle. Many of the genes affecting sarcomere integrity have human homologs for which little or nothing is known
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