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Abstract: NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A subfamily that displays important functional differences with its homolog Nurr1. In particular, the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell lines in which the Nurr1 LBD strongly activates transcription. To gain insight into the structural basis for the distinct activation potentials, we determined the crystal structure of the NGFI-B LBD at 2.4-Å resolution. Superimposition with the Nurr1 LBD revealed a significant shift of the position of helix 12, potentially caused by conservative amino acids exchanges in helix 3 or helix 12. Replacement of the helix 11–12 region of Nurr1 with that of NGFI-B dramatically reduces the transcriptional activity of the Nurr1 LBD. Similarly, mutation of Met414 in helix 3 to leucine or of Leu591 in helix 12 to isoleucine (the corresponding residues found in NGFI-B) significantly affects Nurr1 transactivation. In comparison, swapping the helix 11–12 region of Nurr1 into NGFI-B results in a modest increase of activity. These observations reveal a high sensitivity of LBD activity to changes that influence helix 12 positioning. Furthermore, mutation of hydrophobic surface residues in the helix 11–12 region (outside the canonical co-activator surface constituted by helices 3, 4, and 12) severely affects Nurr1 transactivation. Together, our data suggest that a novel co-regulator surface that includes helix 11 and a specifically positioned helix 12 determine the cell type-dependent activities of the NGFI-B and the Nurr1 LBD.
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Feb 2005
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Abstract: MOLE (mining, organizing, and logging experiments) has been developed to meet the growing data management and target tracking needs of molecular biologists and protein crystallographers. The prototype reported here will become a Laboratory Information Management System (LIMS) to help protein scientists manage the large amounts of laboratory data being generated due to the acceleration in proteome research and will furthermore facilitate collaborations between groups based at different sites. To achieve this, MOLE is based on the data model for protein production devised at the European Bioinformatics Institute (Pajon A, et al., Proteins in press). (C) 2004 Wiley-Liss, Inc.
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Feb 2005
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Theoretical Physics
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Abstract: For the first time, fluctuations in the Dy quadrupole (orbital) moment have been observed in DyB2C2 using inelastic neutron scattering. The observed quasielastic response is decomposed into two components, one reflecting transitions within the doublets (narrow) and the other transitions between the doublets (broad) of the effective Dy quartet ground state. The widths of the narrow and broad components are shown to arise from fluctuations in the magnetic dipole and the electric quadrupole moments, respectively.
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Jan 2005
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Jan 2005
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Abstract: Energy dispersive EXAFS (EDE), using a Laue monochromator on ID24 of the ESRF, and multiple ion monitoring mass spectrometry have been used to monitor the structure and function of alumina-supported rhodium and palladium catalysts within a microreactor. Metallic 5%-Rh/Al2O3 was preformed in situ by hydrogen reduction, and shown to react rapidly with NO at room temperature yielding an oxidised phase. In order for this material to catalyse the reduction of NO by H2 (to N2), it was shown that the metallic phase must be reformed. The ""light-off"" temperature at which the metallic phase was formed and catalysis commenced varied with NO : H2 stoichiometry, this temperature lowering in more reducing conditions. N2O formation was concomitant with the conversion from the oxidised to the metallic phase. The EDE configuration allowed the simultaneous monitoring of structure at both the rhodium and palladium K-edges. Incorporation of a 20% palladium mole fraction into 5%-Rh-Pd/Al2O3 protected rhodium from oxidation and also reduced the light-off temperature, and this is reflected in low coordination number values for the composite Pd to Rh/Pd shell. This favours palladium being preferentially on the surface of the nanoparticles. At higher temperatures there are changes in coordination numbers than imply a redistribution of metal sites under catalytic conditions. Future plans to include infrared spectroscopy as a third simultaneous technique will be outlined.
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Jan 2005
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Abstract: The resonance spectrum of glide-plane forbidden X-ray diffraction have been measured for different temperatures in hexagonal ZnO near the zinc K-edge. This diffraction appears exclusively owing to anisotropy of the Zn atomic scattering factor induced either by thermal motion or by a temperature-independent dipole-quadrupole amplitude. The results provide the first evidence for a complex line shape in the spectrum of thermal motion induced scattering, and the first observation of a dramatic change in resonance spectrum with temperature. The measurements are in excellent agreement with a phenomenological model, based on a combination of constant and a temperature-dependent amplitudes. This model has provided a means of extracting amplitude spectra of each component, and their relative phase. We find that the strongest spectral feature of the room-temperature resonance spectrum arises from a sudden phase change between the two resonant processes. These results are of great importance for better understanding of the temperature effect on the excited electronic states in crystals like hybridization of different orbitals, etc.
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Jan 2005
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Accelerator Physics
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Abstract: The non-linear beam dynamics have been investigated for the non-zero dispersion lattice of the Diamond storage ring. Effects in realistic lattice configuration, where coupling errors and engineering aperture limitations are considered, have been studied here. Frequency Map Analysis together with 6D tracking allows identification of the limiting resonances as well as the loss locations and calculation of the influence of non-linear longitudinal motion on the Touschek lifetime. The sensitivity of the lattice to these effects suggests the identification of a better working point for the machine.
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Jan 2005
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Accelerator Physics
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Abstract: A precise model of an accelerator ring is crucial to achieve ultimate performance both in synchrotron light sources and high energy synchrotrons. Algorithms have been developed to calibrate the linear model of die ring. They have been successfully applied experimentally to determine and correct the linear optics of the machine. More recently the Frequency Map Analysis has been used to model also die non-linear optics. We propose here a technique based on the fit of non-linear spectral lines to recover the non-linear driving terms and to compensate the non-linear field errors around the ring.
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Jan 2005
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Accelerator Physics
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Riccardo
Bartolini
,
M
Belgroune
,
Chris
Christou
,
Vince
Kempson
,
Beni
Singh
,
D
Holder
,
J
Jones
,
S
Smith
,
J
Varley
,
N
Wyles
,
James
Rowland
,
Alan
Baldwin
,
Ian
Martin
Abstract: Diamond is a 3 GeV synchrotron light source under construction at the Rutherford Appleton Laboratory in Oxfordshire (UK)[1]. The accelerator complex consists of a 100 MeV linac, a full-energy booster and a 3 GeV storage ring with 22 straight sections available for insertion devices. Installation of all three accelerators has begun and linac commissioning is due to start in summer 2005. This paper will give an overview of the status of the installation and the progress in accelerator physics studies. The Diamond facility is expected to be operational for users in 2007.
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Jan 2005
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Controls
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Abstract: This paper and our conference paper (Abbott, Altenkirch, Ghani, and McBride, 2003b) explain and analyse the notion of the derivative of a data structure as the type of its one-hole contexts based on the central observation made by McBride (2001). To make the idea precise we need a generic notion of a data type, which leads to the notion of a container, introduced in (Abbott, Altenkirch, and Ghani, 2003a) and investigated extensively in (Abbott, 2003). Using containers we can provide a notion of linear map which is the concept missing from McBride's first analysis. We verify the usual laws of differential calculus including the chain rule and establish laws for initial algebras and terminal coalgebras.
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Jan 2005
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