A Study of Degenerate Four-quark states in SU(2) Lattice Monte Carlo

The energies of four-quark states are calculated for geometries in which the quarks are situated on the corners of a series of tetrahedra and also for geometries that correspond to gradually distorting these tetrahedra into a plane. The interest in tetrahedra arises because they are composed of {\bf three } degenerate partitions of the four quarks into two two-quark colour singlets. This is an extension of earlier work showing that geometries with {\bf two} degenerate partitions (e.g.\ squares) experience a large binding energy. It is now found that even larger binding energies do not result, but that for the tetrahedra the ground and first excited states become degenerate in energy. The calculation is carried out using SU(2) for static quarks in the quenched approximation with $\beta=2.4$ on a $16^3\times 32$ lattice. The results are analysed using the correlation matrix between different euclidean times and the implications of these results are discussed for a model based on two-quark potentials.Comment: Original Raw PS file replace by a tarred, compressed and uuencoded PS fil

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Branching ratio change in K- absorption at rest and the nature of the Lambda(1405)

We investigate in-medium corrections to the branching ratio in K- absorption at rest and their effect on the (positively and negatively) charged pion spectrum. The in-medium corrections are due to Pauli blocking, which arises if the Lambda(1405) is assumed to be a $\bar{K}$-nucleon bound state and leads to a density and momentum dependent mass shift of the Lambda(1405). Requiring that the optical potential as well as the branching ratio are derived from the same elementary T-matrix, we find that the in-medium corrected, density dependent T-matrix gives a better description of the K- absorption reaction than the free, density-independent one. This result suggests that the dominant component of the Lambda(1405) wave function is the $\bar{K}N$ bound state.Comment: 8 Pages, Revtex with epsf, and embedded 8 ps figure

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

Local implicit modeling of blood vessels for interactive simulation

International audienceIn the context of computer-based simulation, contact management requires an accurate, smooth, but still efficient surface model for the blood vessels. A new implicit model is proposed, consisting of a tree of local implicit surfaces generated by skeletons ({\em blobby models}). The surface is reconstructed from data points by minimizing an energy, alternating with an original blob selection and subdivision scheme. The reconstructed models are very efficient for simulation and were shown to provide a sub-voxel approximation of the vessel surface on 5 patients

Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome

hHR23B is one of two human homologs of the Saccharomyces cerevisiae nucleotide excision repair (NER) gene product RAD23 and a component of a protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-C) cell extracts in vitro. Although a small proportion of hHR23B is tightly complexed with the XP-C responsible gene product, XPC protein, a vast majority exists as an XPC-free form, indicating that hHR23B has additional functions other than NER in vivo. Here we demonstrate that the human NER factor hHR23B as well as another human homolog of RAD23, hHR23A, interact specifically with S5a, a subunit of the human 26 S proteasome using the yeast two-hybrid system. Furthermore, hHR23 proteins were detected with S5a at the position where 26 S proteasome sediments in glycerol gradient centrifugation of HeLa S100 extracts. Intriguingly, hHR23B showed the inhibitory effect on the degradation of (125)I-lysozyme in the rabbit reticulocyte lysate. hHR23 proteins thus appear to associate with 26 S proteasome in vivo. From co-precipitation experiments using several series of deletion mutants, we defined the domains in hHR23B and S5a that mediate this interaction. From these results, we propose that part of hHR23 proteins are involved in the proteolytic pathway in cells

A model of methane concentration profiles in the open ocean

Methane-bearing particulate matter formed in the upper ocean layer is allowed to settle and degrade, releasing methane into the water column as a source in one-dimensional advection-diffusion equations. Predicted carbon and methane particulate fluxes are in good agreement with sediment trap data, using parameters of expected magnitude and particulate methane production well within the mixed layer. This suggests a rapid pathway to the atmosphere and reduced effects on methane concentrations below. Vertical advection rates yielding a good fit between methane concentration calculations and data are larger than expected unless methane oxidation is included. This confirms the significance of methane oxidation in shaping open-ocean methane concentration profiles in spite of turnover times of decades. Predictions of the isotopic composition of dissolved methane δ13 C with the one-dimensional model are more difficult, although trends in measured vertical profiles can be reproduced. While this work does not shed light on the purported mechanism of methane generation in the upper ocean, it shows that methane of particulate origin is sufficient to explain observed open-ocean methane concentrations

Notes on the modeling of methane in aging hydrothermal plumes

Marine hydrothermal vent fields represent a unique environment for the study of aerobic microbial methane oxidation because of high methane concentrations and limited spatial and temporal scales. Earlier data collected in lateral plumes at the Endeavour Segment of the Juan de Fuca Ridge, including methane concentration, methane oxidation rate and stable carbon isotopic composition (δ13C), are carefully interpreted with a suite of simple analytical models. Methane oxidation is defined with a rate constant k as a first order process with respect to both substrate and methanotroph concentration. This elementary formalism coupled with simplified representations of advection and diffusion through the lateral plume is sufficient to reproduce salient features of the data: maximum methane turnover times of about a week 2 km from the vent field location and stable carbon isotopic enrichment from -47‰ to values exceeding -5‰ over a distance of 15 km. Results suggest that k is of order 10-8 (nM-s)-1 at local conditions and that methane oxidizing bacteria hold about 12 fg of carbon per cell

Biological Insights into the Expression of Translation Initiation Factors from Recombinant CHOK1SV Cell Lines and their Relationship to Enhanced Productivity

Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAb) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop; eukaryotic initiation factors (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A) binding protein (PABP) 1 and PABP interacting protein 1 (PAIP1) across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilise knowledge of the amounts of these factors to build predictive models for, and use cluster analysis to identify, high-producing cell lines. This study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity

The uses of coherent structure (Dryden Lecture)

The concept of coherent structure in turbulent flow is a revolutionary idea which is being developed by evolutionary means. The main objective of this review is to list some solid achievements, showing what can be done by using the concept of coherent structure that cannot be done without it. The nature of structure is described in terms of some related concepts, including celerity, topology, and the phenomenon of coalescence and splitting of structure. The main emphasis is on the mixing layer, as the one flow whose structure is well enough understood so that technical applications are now being made in problems of mixing and chemistry. An attempt is made to identify some conceptual and experimental obstacles that stand in the way of progress in other technically important flows, particularly the turbulent boundary layer. A few comments are included about the role of structure in numerical simulations and in current work on manipulation and control of turbulent flow. Some recent developments are cited which suggest that the time is nearly right for corresponding advances to occur in turbulence modeling