Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage

The rad2 mutant of Schizosaccharomyces pombe is sensitive to UV irradiation and deficient in the repair of UV damage. In addition, it has a very high degree of chromosome loss and/or nondisjunction. We have cloned the rad2 gene and have shown it to be a member of the Saccharomyces cerevisiae RAD2/S. pombe rad13/human XPG family. Using degenerate PCR, we have cloned the human homolog of the rad2 gene. Human cDNA has 55% amino acid sequence identity to the rad2 gene and is able to complement the UV sensitivity of the rad2 null mutant. We have thus isolated a novel human gene which is likely to be involved both in controlling the fidelity of chromosome segregation and in the repair of UV-induced DNA damage. Its involvement in two fundamental processes for maintaining chromosomal integrity suggests that it is likely to be an important component of cancer avoidance mechanisms

Diagnostic delay in a case of T-cell neurolymphomatosis

A 69-year-old woman presented with severe subacute painful meningoradiculoneuritis. Neurophysiology showed a patchy, proximal axonal process with widespread denervation. Cerebrospinal fluid (CSF) was lymphocytic (normal T-cell predominant) with negative cytology. MRI revealed multiple sites of enhancement, but fluorodeoxyglucose positron emission tomography was negative. Bone marrow aspirate and trephine (BMAT) showed no evidence of a lymphoproliferative condition. Right brachial plexus biopsy demonstrated mixed T-cell/B-cell endoneurial inflammation not fulfilling criteria for vasculitis. She was stabilised with high-dose steroids and cyclophosphamide, followed by mycophenolate for inflammatory myeloradiculoneuritis. However, symptoms recurred when prednisolone was weaned. Although T-cell receptor gene analysis from the initial CSF demonstrated clonal rearrangements, it was only when the same clones were identified on two repeat BMATs and CSF that T-cell neurolymphomatosis, an exceedingly rare condition, was diagnosed. This case highlights the diagnostic challenge in peripheral neurolymphomatosis related to patchy disease, variable sensitivity and specificity of investigative tools, and the influence of therapies on traditional cytological definitions of lymphoma. The clinical picture, exhaustive exclusion of alternative causes and the persistence of an abnormal T-cell clone ultimately lead to a diagnostic consensus between specialist neurology and haematology clinicians

Covering problems in edge- and node-weighted graphs

This paper discusses the graph covering problem in which a set of edges in an edge- and node-weighted graph is chosen to satisfy some covering constraints while minimizing the sum of the weights. In this problem, because of the large integrality gap of a natural linear programming (LP) relaxation, LP rounding algorithms based on the relaxation yield poor performance. Here we propose a stronger LP relaxation for the graph covering problem. The proposed relaxation is applied to designing primal-dual algorithms for two fundamental graph covering problems: the prize-collecting edge dominating set problem and the multicut problem in trees. Our algorithms are an exact polynomial-time algorithm for the former problem, and a 2-approximation algorithm for the latter problem, respectively. These results match the currently known best results for purely edge-weighted graphs.Comment: To appear in SWAT 201

Multivariate Topology Simplification

Topological simplification of scalar and vector fields is well-established as an effective method for analysing and visualising complex data sets. For multivariate (alternatively, multi-field) data, topological analysis requires simultaneous advances both mathematically and computationally. We propose a robust multivariate topology simplification method based on “lip”-pruning from the Reeb space. Mathematically, we show that the projection of the Jacobi set of multivariate data into the Reeb space produces a Jacobi structure that separates the Reeb space into simple components. We also show that the dual graph of these components gives rise to a Reeb skeleton that has properties similar to the scalar contour tree and Reeb graph, for topologically simple domains. We then introduce a range measure to give a scaling-invariant total ordering of the components or features that can be used for simplification. Computationally, we show how to compute Jacobi structure, Reeb skeleton, range and geometric measures in the Joint Contour Net (an approximation of the Reeb space) and that these can be used for visualisation similar to the contour tree or Reeb graph

South‐North Hemispheric Asymmetry of the FAE Distribution Around the Cusp Region: Cluster Observation

Cluster data from late July to early October were used to study the distribution of field‐aligned electron (FAE) events around the two cusps. An FAE event was defined as electron parallel flux >3 × 108 (cm2 s)−1. The total number of FAE events around the two cusps was basically identical, but downward FAE events prevailed in the south and upward FAE events in the north. In the southern cusp, the peak of the FAE events distribution versus altitude was about 1.3 RE higher and the peak of the FAE events distribution versus invariant latitude (ILAT) was about 4° ILAT lower. Only the downward FAEs around the southern cusp had a second ILAT peak, which was located about 11° higher than the main peak. The normalized number of FAEs showed nearly the same features as the unnormalized number of the FAEs events. These results indicated a north‐south asymmetry of the FAE distribution around the two cusps. Some causes for the asymmetry are discussed, the main ones being the asymmetry of the magnetospheric configuration resulting from geomagnetic dipolar tilt and solar wind flows, the interplanetary magnetic field asymmetry related to the magnetosphere, and the difference of ionospheric conductivity in the two hemispheres. Various solar wind‐magnetosphere interaction processes, such as quasi‐viscous interaction and reconnection, are responsible for the asymmetry, too. The second distribution peak (at higher ILAT) of the downward FAE events around the southern cusp corresponded to high solar wind speed and may be associated with the northward interplanetary magnetic field Bz field‐aligned current at low altitude. This requires further studies, however

Inflating wormholes in the braneworld models

The braneworld model, in which our Universe is a three-brane embedded in a five-dimensional bulk, allows the existence of wormholes, without any violation of the energy conditions. A fundamental ingredient of traversable wormholes is the violation of the null energy condition (NEC). However, in the brane world models, the stress energy tensor confined on the brane, threading the wormhole, satisfies the NEC. In conventional general relativity, wormholes existing before inflation can be significantly enlarged by the expanding spacetime. We investigate the evolution of an inflating wormhole in the brane world scenario, in which the wormhole is supported by the nonlocal brane world effects. As a first step in our study we consider the possibility of embedding a four-dimensional brane world wormhole into a five dimensional bulk. The conditions for the embedding are obtained by studying the junction conditions for the wormhole geometry, as well as the full set of the five dimensional bulk field equations. For the description of the inflation we adopt the chaotic inflation model. We study the dynamics of the brane world wormholes during the exponential inflation stage, and in the stage of the oscillating scalar field. A particular exact solution corresponding to a zero redshift wormhole is also obtained. The resulting evolution shows that while the physical and geometrical parameters of a zero redshift wormhole decay naturally, a wormhole satisfying some very general initial conditions could turn into a black hole, and exist forever.Comment: 30 pages, no figures, accepted for publication in CQ

The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

The rad18 mutant of Schizosaccharomyces pombe is very sensitive to killing by both UV and ¿ radiation. We have cloned and sequenced the rad18 gene and isolated and sequenced its homolog from Saccharomyces cerevisiae, designated RHC18. The predicted Rad18 protein has all the structural properties characteristic of the SMC family of proteins, suggesting a motor function- the first implicated in DNA repair. Gene deletion shows that both rad18 and RHC18 are essential for proliferation. Genetic and biochemical analyses suggest that the product of the rad18 gene acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair. This second repair pathway involves the products of the rhp51 gene (the homolog of the RAD51 gene of S. cerevisiae) and the rad2 gene

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor‐α, transforming growth factor‐β, and c‐Ha‐ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10‐day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose‐related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose. (Hepatology 1994;20:1237–1241). Copyright © 1994 American Association for the Study of Liver Disease