Timescales for pluton growth, magma-chamber formation and super-eruptions.

Generation of silicic magmas leads to emplacement of granite plutons, huge explosive volcanic eruptions and physical and chemical zoning of continental and arc crust1-7. Whereas timescales for silicic magma generation in the deep and middle crust are prolonged8, magma transfer into the upper crust followed by eruption is episodic and can be rapid9-12. Ages of inherited zircons and sanidines from four Miocene ignimbrites in the Central Andes indicate a gap of 4.6 Myr between initiation of pluton emplacement and onset of super-eruptions, with a 1-Myr cyclicity. We show that inherited zircons and sanidine crystals were stored at temperatures <470 °C in these plutons before incorporation in ignimbrite magmas. Our observations can be explained by silicic melt segregation in a middle-crustal hot zone with episodic melt ascent from an unstable layer at the top of the zone with a timescale governed by the rheology of the upper crust. After thermal incubation of growing plutons, large upper-crustal magma chambers can form in a few thousand years or less by dike transport from the hot-zone melt layer. Instability and disruption of earlier plutonic rock occurred in a few decades or less just before or during super-eruptions.

Formation and dynamics of magma reservoirs.

The emerging concept of a magma reservoir is one in which regions containing melt extend from the source of magma generation to the surface. The reservoir may contain regions of very low fraction intergranular melt, partially molten rock (mush) and melt lenses (or magma chambers) containing high melt fraction eruptible magma, as well as pockets of exsolved magmatic fluids. The various parts of the system may be separated by a sub-solidus rock or be connected and continuous. Magma reservoirs and their wall rocks span a vast array of rheological properties, covering as much as 25 orders of magnitude from high viscosity, sub-solidus crustal rocks to magmatic fluids. Time scales of processes within magma reservoirs range from very slow melt and fluid segregation within mush and magma chambers and deformation of surrounding host rocks to very rapid development of magma and fluid instability, transport and eruption. Developing a comprehensive model of these systems is a grand challenge that will require close collaboration between modellers, geophysicists, geochemists, geologists, volcanologists and petrologists. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.

Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.

We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity.

Maintained serum sodium in male ultra-marathoners--the role of fluid intake, vasopressin, and aldosterone in fluid and electrolyte regulation.

Exercise-associated hyponatremia (EAH) is a well know electrolyte disorder in endurance athletes. Although fluid overload is the most like etiology, recent studies, however, argued whether EAH is a disorder of vasopressin secretion. The aims of the present study were to investigate (i) the prevalence of EAH in male ultra-marathoners and (ii) whether fluid intake, aldosterone or vasopressin, as measured by copeptin, were associated with post-race serum sodium concentration ([Na+]). In 50 male ultra-marathoners in a 100 km ultra-marathon, serum [Na+], aldosterone, copeptin, serum and urine osmolality, and body mass were measured pre- and post-race. Fluid intake, renal function parameters and urine excretion were measured. No athlete developed EAH. Copeptin and aldosterone increased; a significant correlation was found between the change in copeptin and the change in serum [Na+], no correlation was found between aldosterone and serum [Na+]. Serum [Na+] increased by 1.6%; body mass decreased by 1.9 kg. The change in serum [Na+] and body mass correlated significantly and negatively. The fluid intake of ~ 0.58 l/h was positively related to the change in body mass and negatively to both post-race serum [Na+] and the change in serum [Na+]. We conclude that serum [Na+] was maintained by both the mechanisms of fluid intake and the hormonal regulation of vasopressin.

New model systems provide insights into Myc-induced transformation.

The ability of Myc to promote cellular transformation is well established; however, a better understanding of the mechanisms through which Myc mediates tumorigenesis is essential for the development of therapeutic approaches to target this potent oncoprotein. Structure-function studies in rodent fibroblast cells have provided the basis for much of our current understanding of these mechanisms. To build on these approaches, we have characterized three novel human cell line models of Myc-dependent transformation: MCF10A, SH-EP Tet21/N-Myc, and LF1/TERT/LT/ST cells. We have also evaluated Myc family proteins (c-Myc and L-Myc), a naturally occurring isoform of Myc (MycS), and a set of N-terminal domain mutants (ΔMBII, W135E, T58A) for their ability to promote anchorage-independent growth in these models. Taken together, these results provide the field with three new human cell-based models to study Myc activity, highlight the importance of cellular context, and challenge the paradigm that the ability of Myc to promote tumorigenesis is exclusively MBII-dependent.

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

The Ensembl genome database project.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

Bubble shapes and orientations in low Re simple shear flow.

We present measurements of shape and orientation of air bubbles in a viscous Newtonian fluid deformed by simple shear. The apparatus is a variation of the "parallel band" device developed by G. I. Taylor. Previous experimental studies on low viscosity ratio, low Reynolds number (Re << 1) bubble deformation have focussed on either small or large deformations (mostly small deformation) and have only qualitatively examined the orientation of bubbles except for small deformations. Our data set spans both the theoretical small deformation and high deformation limits. With these data we confirm theoretical relationships and assess the range of capillary numbers (Ca) over which theoretical relationships for shape and orientation of bubbles are appropriate. We also examine the geometry of deformed bubbles as they relax to a spherical shape once shear stresses are removed. Our data indicate that for extremely small Reynolds numbers and viscosity ratios, the small deformation theoretical relationship first developed by Taylor, is a good approximation for Ca<0.5. The large deformation results for both shape and bubble orientation derived by Hinch and Acrivos agree with our data for Ca>1 and Ca>0.5, respectively.

Implications of using high contrast mammography X-ray film-screen combinations.

The objective of this study was to determine the implications of using Fuji AD-M and Kodak min-R 2000, two high contrast X-ray film types developed for mammography. Evaluation of the Fuji AD-M film was divided into two parts. The first part was a contralateral comparison between mammograms using Fuji AD-M and Fuji UM-MA HC film-screen combinations. Fuji AD-M contrast was about 25% higher than that of Fuji UM-MA HC. The effect of increased contrast on image quality was investigated by visually grading the quality of information in different parts of each mammogram. Fuji AD-M film was generally judged to be better for overall diagnosis. However, 2.3% of mammograms produced using Fuji AD-M film were not acceptable and might have led to a technical recall of the patient. In the second part of this study, sets of mammograms from women attending mobile screening units were reviewed. One unit used Fuji AD-M film and the other used Kodak min-R 2000 film. Both samples of mammograms were digitized and analysed. The average film gradients between an optical density (OD) of 0.25 and 2.00 above base plus fog were 4.38 for Fuji AD-M film and 3.77 for Kodak min-R 2000 film. The main breast regions of the mammograms were judged to be satisfactorily displayed when breast tissues were above ODs of approximately 0.6 for Fuji AD-M film and 0.8 for Kodak min-R 2000 film.

Loss of tuberin, the tuberous-sclerosis-complex-2 gene product is associated with angiogenesis.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2. METHODS: Immunohistochemical analyses of human angiofibromas were performed using antibodies directed against tuberin and angiogenic growth factors. Proliferation of human dermal microvascular endothelial cells (HDMEC) was determined after incubation with the supernatants of TSC2 (+/+) and TSC2 (-/-) rat embryonic fibroblasts (REF) that were derived from the Eker strain. RESULTS: Loss of the expression of tuberin was observed in the interstitial cells of 13 of 39 angiofibromas. The expression of tuberin was retained in the vascular cells. In all analyzed angiofibromas, the angiogenic factors bFGF, PD-ECGF, VEGF and angiogenin were detected in the interstitial cells and/or vascular cells. Expression of PDGF-B and TGF-beta1 was weak. Tissue culture supernatants from TSC2 (-/-) REF stimulated the growth of HDMEC significantly more than supernatants from TSC2 (+/+) REF. CONCLUSION: A functional loss of tuberin may stimulate vascular growth.

Human papillomavirus in cutaneous squamous cell carcinoma and cervix of a patient with psoriasis and extensive ultraviolet radiation exposure.

"High-risk" human papillomaviruses (HPVs) are associated with intraepithelial neoplasia and cancer of the uterine cervix. HPV has also been found in nonmelanoma skin cancer (NMSC), especially in squamous cell carcinomas (SCCs) of immunosuppressed patients. Recently, lesions of psoriasis have been shown to harbor HPV, and patients with psoriasis often have a history of extensive therapy with ultraviolet radiation (UVR). UVR is the major known risk factor in the occurrence of NMSC, in which HPV may be a cofactor for SCC. We report an otherwise healthy, nonimmunosuppressed patient with psoriasis who had a history of extensive exposure to UVR and experienced multiple SCCs on UV-exposed body sites. By the polymerase chain reaction method, we detected HPV in 5 of 9 SCCs. Automated sequencing showed HPV types 12 and 17. Only 1 of 3 normal skin specimens was HPV positive (HPV type 17). This positive specimen was from UV-exposed skin; one of the two HPV-negative, normal skin specimens was located on a body site not exposed to sun. In addition, HPV type 62 was found in a brush specimen of the uterine cervix. This case report suggests an association between psoriasis, HPV infection, and UVR exposure, in onset of SCC.

Effect of automatic kV selection on dose and contrast for a mammographic X-ray system.

The effect of automatic tube potential (kV) selection on breast dose and contrast has been assessed using a Philips MammoDiagnost 3000 mammography X-ray set. The performance of the X-ray set using automatic kV selection has been compared with that found using a fixed kV of 28. The AUTOKV mode selected 25 kV for breasts with thickness up to about 50 mm, which increased the contrast by 5-10%, and increased the mean glandular dose (MGD) per film by, on average, 30-40%. For large breasts with a compressed thickness of 70 mm and above, kVs up to 30 were selected so that the average MGD per film was reduced by 19% from 3.62 to 2.94 mGy, with an estimated loss in contrast of about 4-8%. For all breasts the mean MGD per film was 1.85 +/- 0.05 mGy where AUTOKV was used, and 1.74 +/- 0.08 mGy per film when 28 kV was used. The overall image quality of the mammograms was found to be higher when AUTOKV was used. Overall, the AUTOKV facility on this X-ray set generally worked well and resulted in slightly higher contrast and slightly better image quality at the price of a small increase in the average dose for this patient group when compared with the usual UK procedure of using a fixed 28 kV.

Short communication: kilovoltage measurement with rhodium target and filters on mammography X-ray machines.

X-ray machines used for mammography have, until recently, almost exclusively employed molybdenum (Mo) as anode material and filtration. In the UK, the RMI model 232 kVp meter is used extensively for the measurement of kilovoltage on such equipment. This unit is provided with switchable internal calibration only for molybdenum and molybdenum, or tungsten and aluminium, as anode and filtration, respectively. However, rhodium (Rh) has recently been introduced for filtration with either a molybdenum or rhodium anode in mammography equipment but, as yet, calibration facilities are not available for rhodium spectra. In this work, appropriate corrections for readings obtained with the RMI 232 kVp meter are derived for use with rhodium as filtration material with either molybdenum or rhodium anode material. An intercomparison between measurements made with four RMI model 232 kVp meters and nine IGE DMR X-ray sets was undertaken. The reproducibility of the instruments was confirmed and measurements of tube potential made on each of the X-ray sets pooled. Measurements were made from a nominal 25-35 kVp using Mo/Mo, Mo/Rh and Rh/Rh target/filter combinations. Corrections for readings obtained with Mo/Rh and Rh/Rh were produced by comparison with readings obtained with Mo/Mo, assuming stability of tube potential between anodes. The results are compared with data recently produced by the manufacturer of the meter.

Dose and image quality in mammography with an automatic beam quality system.

Radiation dose, contrast and image quality for automatic beam quality selection (OPDOSE) with the Siemens Mammomat 3000 has been investigated for different breast thicknesses and compared with those found using manually set tube potentials and a molybdenum target and filter. Automatic beam quality selection was found to have a negligible effect for breasts with a compressed breast thickness of less than 45 mm. However, for larger breasts substantial dose savings were achieved for a loss in contrast. For mammograms of compressed breast with a thickness in excess of 60 mm the mean glandular dose (MGD) per film was 2.90 mGy for manually selected tube potentials with a molybdenum/molybdenum target filter combination as compared with 1.87 mGy using 26 kVp and a tungsten target with rhodium filtration. The contrast loss in using OPDOSE was measured with a test object to be about 10% for breast thicknesses in excess of 45 mm. The standard breast model, which assumes a 50% glandular content, did not provide a good fit to the MGD for women attending for breast screening in the age range 50 to 64 years.