Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours

AbstractMetastatic cancer in adults usually has a fatal outcome. In contrast, advanced testicular germ cell tumours are cured in over 80% of patients using cisplatin-based combination chemotherapy [1]. An understanding of why these cells are sensitive to chemotherapeutic drugs is likely to have implications for the treatment of other types of cancer. Earlier measurements indicate that testis tumour cells are hypersensitive to cisplatin and have a low capacity to remove cisplatin-induced DNA damage from the genome [2,3]. We have investigated the nucleotide excision repair (NER) capacity of extracts from the well-defined 833K and GCT27 human testis tumour cell lines. Both had a reduced ability to carry out the incision steps of NER in comparison with extracts from known repair-proficient cells. Immunoblotting revealed that the testis tumour cells had normal amounts of most NER proteins, but low levels of the xeroderma pigmentosum group A protein (XPA) and the ERCC1–XPF endonuclease complex. Addition of XPA specifically conferred full NER capacity on the testis tumour extracts. These results show that a low XPA level in the testis tumour cell lines is sufficient to explain their poor ability to remove cisplatin adducts from DNA and might be a major reason for the high cisplatin sensitivity of testis tumours. Targeted inhibition of XPA could sensitise other types of cells and tumours to cisplatin and broaden the usefulness of this chemotherapeutic agent

The reproducibility of T2 relaxation time measurement of knee cartilage in women aged over 50 [Abstract]

The reproducibility of T2 relaxation time measurement of knee cartilage in women aged over 50 [Abstract

Adherence and feasibility of a high impact exercise intervention in post-menopausal women [Abstract]

Adherence and feasibility of a high impact exercise intervention in post-menopausal women [Abstract

Effect of high impact exercise on femoral neck bone mineral density and T2 relaxation times of articular cartilage in postmenopausal women [Abstract]

Effect of high impact exercise on femoral neck bone mineral density and T2 relaxation times of articular cartilage in postmenopausal women [Abstract

A QCQP Approach to Triangulation

Triangulation of a three-dimensional point from at least two noisy 2-D images can be formulated as a quadratically constrained quadratic program. We propose an algorithm to extract candidate solutions to this problem from its semidefinite programming relaxations. We then describe a sufficient condition and a polynomial time test for certifying when such a solution is optimal. This test has no false positives. Experiments indicate that false negatives are rare, and the algorithm has excellent performance in practice. We explain this phenomenon in terms of the geometry of the triangulation problem.Comment: 14 pages, to appear in the proceedings of the 12th European Conference of Computer Vision, Firenze, Italy, 7-13 October 201

Simultaneous Determination of Thermal Conductivity and Specific Heat for Refractory Materials

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66352/1/j.1151-2916.1990.tb07594.x.pd

Large-scale pathways-based association study in amyotrophic lateral sclerosis

Sporadic amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, most likely results from complex genetic and environmental interactions. Although a number of association studies have been performed in an effort to find genetic components of sporadic ALS, most of them resulted in inconsistent findings due to a small number of genes investigated in relatively small sample sizes, while the replication of results was rarely attempted. Defects in retrograde axonal transport, vesicle trafficking and xenobiotic metabolism have been implicated in neurodegeneration and motor neuron death both in human disease and animal models. To assess the role of common genetic variation in these pathways in susceptibility to sporadic ALS, we performed a pathway-based candidate gene case-control association study with replication. Furthermore, we determined reliability of whole genome amplified DNA in a large-scale association study. In the first stage of the study, 1277 putative functional and tagging SNPs in 134 genes spanning 8.7 Mb were genotyped in 822 British sporadic ALS patients and 872 controls using whole genome amplified DNA. To detect variants with modest effect size and discriminate among false positive findings 19 SNPs showing a trend of association in the initial screen were genotyped in a replication sample of 580 German sporadic ALS patients and 361 controls. We did not detect strong evidence of association with any of the genes investigated in the discovery sample (lowest uncorrected P-value 0.00037, lowest permutation corrected P-value 0.353). None of the suggestive associations was replicated in a second sample, further excluding variants with moderate effect size. We conclude that common variation in the investigated pathways is unlikely to have a major effect on susceptibility to sporadic ALS. The genotyping efficiency was only slightly decreased (∼1%) and genotyping quality was not affected using whole genome amplified DNA. It is reliable for large scale genotyping studies of diseases such as ALS, where DNA sample collections are limited because of low disease prevalence and short survival time. © 2007 The Author(s)

Recovery of release cloud from laser shock-loaded graphite and hydrocarbon targets: in search of diamonds

This work presents first insights into the dynamics of free-surface release clouds from dynamically compressed polystyrene and pyrolytic graphite at pressures up to 200 GPa, where they transform into diamond or lonsdaleite, respectively. These ejecta clouds are released into either vacuum or various types of catcher systems, and are monitored with high-speed recordings (frame rates up to 10 MHz). Molecular dynamics simulations are used to give insights to the rate of diamond preservation throughout the free expansion and the catcher impact process, highlighting the challenges of diamond retrieval. Raman spectroscopy data show graphitic signatures on a catcher plate confirming that the shock-compressed PS is transformed. First electron microscopy analyses of solid catcher plates yield an outstanding number of different spherical-like objects in the size range between ten(s) up to hundreds of nanometres, which are one type of two potential diamond candidates identified. The origin of some objects can unambiguously be assigned, while the history of others remains speculative

The underlying causes of military outsourcing in the USA and UK: bridging the persistent gap between ends, ways and means since the beginning of the Cold War

This article reappraises the two most-studied country cases of military outsourcing: the USA and the UK. It argues that the contemporary wave of military contracting stretches back to the beginning of the cold war and not only to the demobilisation of armies in the 1990s or the neoliberal reforms introduced since the 1980s. It traces the political, technological and ideational developments that laid the groundwork for these reforms and practices since the early cold war and account for its endurance today. Importantly, it argues that a persistent gap between strategic objectives and resources, i.e. the challenge to reconcile ends and means, is an underlying driver of military contracting in both countries. Contemporary contracting is thus most closely tied to military support functions in support of wider foreign and defence political objectives. Security services in either state may not have been outsourced so swiftly, if at all, without decades of experience in outsourcing military logistics functions and the resultant vehicles, processes and familiarities with public-private partnerships. The article thus provides a wider and deeper understanding of the drivers of contractualisation, thereby improving our understanding of both its historical trajectory and the determinants of its present and potential futures