Lorentz's model with dissipative collisions

Propagation of a particle accelerated by an external field through a scattering medium is studied within the generalized Lorentz model allowing inelastic collisions. Energy losses at collisions are proportional to $(1-\alpha^{2})$, where $0\le\alpha\le 1$ is the restitution coefficient. For $\alpha =1$ (elastic collisions) there is no stationary state. It is proved in one dimension that when $\alpha <1$ the stationary state exists . The corresponding velocity distribution changes from a highly asymmetric half-gaussian ($\alpha =0$) to an asymptotically symmetric distribution $\sim {\rm exp}[-(1-\alpha)v^{4}/2]$, for $\alpha\to 1$. The identical scaling behavior in the limit of weak inelasticity is derived in three dimensions by a self-consistent perturbation analysis, in accordance with the behavior of rigorously evaluated moments. The dependence on the external field scales out in any dimension, predicting in particular the stationary current to be proportional to the square root of the external acceleration.Comment: 13 pages, no figures, submitted to Physica

In search of Robert Bruce, part III: medieval royal burial at Dunfermline and the tomb investigations of 1818–19

This article challenges two orthodoxies concerning Dunfermline's medieval church and abbey. It argues that David I and Malcolm IV were buried not with Robert Bruce, his queen, and Alexander III, but with Queen Margaret (died 1093), her husband, three of David's brothers, and Alexander III's first wife, as the earliest royal burial cluster. This argument dovetails with a reappraisal of the evolution of the medieval abbey. It is concluded that when dedicated in 1150, David's abbey was largely coextensive with his mother's church, only achieving cruciform status by 1180 and Queen Margaret's first translation. Reassigning David I and Malcom IV to another burial cluster strengthens the case for identifying the incumbent of the tomb discovered and excavated at Dunfermline in 1818–19 as Robert Bruce, as also argued for in the two other articles in this series

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

Profiles of SUMO and ubiquitin conjugation in an Alzheimer's disease model

► Global levels of ubiquitinated proteins increased in the hippocampus of Tg2576 mice. ► No global changes in either SUMO-1 or SUMO-2/3 conjugation in any brain regions analysed. ► SUMO conjugating and deconjugating enzymes, UBC9 and SENP-1, unaltered in Tg2576 mice. ► Total levels of AMPA and kainate receptors were also unaffected in Tg2576 mice. ► Posttranslational modification by ubiquitin may play a role in Alzheimer's disease

Genomic presence of recombinant porcine endogenous retrovirus in transmitting miniature swine

The replication of porcine endogenous retrovirus (PERV) in human cell lines suggests a potential infectious risk in xenotransplantation. PERV isolated from human cells following cocultivation with porcine peripheral blood mononuclear cells is a recombinant of PERV-A and PERV-C. We describe two different recombinant PERV-AC sequences in the cellular DNA of some transmitting miniature swine. This is the first evidence of PERV-AC recombinant virus in porcine genomic DNA that may have resulted from autoinfection following exogenous viral recombination. Infectious risk in xenotransplantation will be defined by the activity of PERV loci in vivo

SOC in a population model with global control

We study a plant population model introduced recently by J. Wallinga [OIKOS {\bf 74}, 377 (1995)]. It is similar to the contact process (`simple epidemic', `directed percolation'), but instead of using an infection or recovery rate as control parameter, the population size is controlled directly and globally by removing excess plants. We show that the model is very closely related to directed percolation (DP). Anomalous scaling laws appear in the limit of large populations, small densities, and long times. These laws, associated critical exponents, and even some non-universal parameters, can be related to those of DP. As in invasion percolation and in other models where the r\^oles of control and order parameters are interchanged, the critical value $p_c$ of the wetting probability $p$ is obtained in the scaling limit as singular point in the distribution of infection rates. We show that a mean field type approximation leads to a model studied by Y.C. Zhang et al. [J. Stat. Phys. {\bf 58}, 849 (1990)]. Finally, we verify the claim of Wallinga that family extinction in a marginally surviving population is governed by DP scaling laws, and speculate on applications to human mitochondrial DNA.Comment: 19 pages, with 10 ps-figured include

Structural dynamics and ligand binding in kynurenine-3- monooxygenase

Kynurenine 3-monooxygenase is a FAD-dependent aromatic hydroxylase (FAH) which is a widely suggested therapeutic target for controlling the balance of bioactive metabolite levels produced by the mammalian kynurenine pathway (KP). Prior to starting this work no structural information was known for the enzyme, with studies of the human form complicated by the presence of a C-terminal transmembrane helix. The bacterial Pseudomonas fluorescens enzyme (PfKMO) lacks the transmembrane region and has been previously characterised by Crozier-Reabe and Moran [1, 2]. Therefore PfKMO, which shares 32 % sequence identity with the human enzyme, was selected as a target for structure solution. Initial substrate bound PfKMO crystals showed poor X-ray diffraction. Subsequent growth optimisation and the generation of a C252S/C461S PfKMO mutant (dm2) yielded crystals suitable for structure solution. Selenomethioninelabelled substrate bound dm2 crystals were used to solve the first structure to a resolution of 3.40 Å. With just one protein molecule per asymmetric unit, a high solvent content was responsible for the poor diffraction properties of this crystal form. The overall fold resembled that of other FAH enzymes with a Rossmann-fold based FADbinding domain above a buried substrate binding pocket. Interestingly PfKMO possesses an additional, novel C-terminal domain that caps the back of the substrate-binding pocket on the opposite side to the flavin. Residues proposed to be involved in substrate binding were identified and shown to be highly conserved among mammalian KMO sequences. Subsequently single crystals of substrate-free dm2 PfKMO were obtained and showed significantly stronger diffraction due to new lattice packing in an orthorhombic space group bearing four molecules per asymmetric unit. The structure was solved to a resolution of 2.26 Å and revealed a clear conformational change of the novel C-terminal domain. This movement opens a potential route of substrate/product exchange between bulk solvent and the active site. The investigation of a set of C-terminal mutants further explored the relevance and mechanics of the conformational change. In addition the presence of chloride ions in the substrate-free crystal growth solution caused a small number of localised subtle alterations to the structure, with a potential chloride binding site identified adjacent to the flavin cofactor. This may have relevance for the observed inhibition of PfKMO activity by monovalent anions – a feature widely common to FAH enzymes [3]. The first discovered KMO inhibitors were analogues of the substrate L-Kyn, however one such compound (m-NBA) was recently shown to instigate uncoupled NADPH oxidation leading to the release of cytotoxic hydrogen peroxide [1]. A set of substrate analogues were tested and characterised for inhibition of PfKMO. The picture was shown to be complex as some substrate analogues completely inhibited the enzyme whilst the binding of some still stimulated low-levels of NADPH oxidation. Crystallographic studies with m-NBA and 3,4-dichlorobenzoylalanine (3,4-CBA) bound revealed indistinguishable structures from that of substrate-bound PfKMO. These studies suggest that the analogue 3,4CBA is a potent PfKMO inhibitor whose therapeutic potential may be re-visited. The previous most potent KMO inhibitor whose structure was not analogous to the substrate was Ro 61-8048 [4], which unfortunately did not pass pre-clinical safety tests. A novel series of 1,2,4-oxadiazole amides based on the structure of Ro 61-8048 was created by Gavin Milne (PhD, University of St Andrews) and tested on PfKMO. Rounds of refinement led to the discovery and refinement of low nanomolar competitive inhibitors of the bacterial enzyme. PfKMO was co-crystallised with each of the four most potent compounds forming a third different lattice arrangement, which yielded structures to resolutions of 2.15-2.40 Å. The structures displayed conformational changes resembling the substrate-free fold possibly caused by displacement of a crucial substrate-binding residue, R84. Overall the wealth of structural data obtained may be transferable to predictions about the structural features of human KMO and to the rational design of therapeutic inhibitors. The potent novel inhibitors tested may additionally present a new exciting development for the therapeutic inhibition of human KMO

A solenoidal electron spectrometer for a precision measurement of the neutron β\beta-asymmetry with ultracold neutrons

We describe an electron spectrometer designed for a precision measurement of the neutron $\beta$-asymmetry with spin-polarized ultracold neutrons. The spectrometer consists of a 1.0-Tesla solenoidal field with two identical multiwire proportional chamber and plastic scintillator electron detector packages situated within 0.6-Tesla field-expansion regions. Select results from performance studies of the spectrometer with calibration sources are reported.Comment: 30 pages, 19 figures, 1 table, submitted to NIM