Modeling subauroral polarization streams equatorward of the plasmapause footprints

Pint?r, B.; Thom, S. D.; Balthazor, R.; Vo, H.; Bailey, G. J., Modeling subauroral polarization streams equatorward of the plasmapause footprints, Journal of Geophysical Research, Volume 111, Issue A10, CiteID A10306 RAE2008

Physiological levels of PTEN control the size of the cellular Ins(1,3,4,5,6)P5 pool

To understand how a signaling molecule's activities are regulated, we need insight into the processes controlling the dynamic balance between its synthesis and degradation. For the Ins(1,3,4,5,6)P5 signal, this information is woefully inadequate. For example, the only known cytosolic enzyme with the capacity to degrade Ins(1,3,4,5,6)P5 is the tumour-suppressor PTEN [J.J. Caffrey, T. Darden, M.R. Wenk, S.B. Shears, FEBS Lett. 499 (2001) 6 ], but the biological relevance has been questioned by others [E.A. Orchiston, D. Bennett, N.R. Leslie, R.G. Clarke, L. Winward, C.P. Downes, S.T. Safrany, J. Biol. Chem. 279 (2004) 1116 ]. The current study emphasizes the role of physiological levels of PTEN in Ins(1,3,4,5,6)P5 homeostasis. We employed two cell models. First, we used a human U87MG glioblastoma PTEN-null cell line that hosts an ecdysone-inducible PTEN expression system. Second, the human H1299 bronchial cell line, in which PTEN is hypomorphic due to promoter methylation, has been stably transfected with physiologically relevant levels of PTEN. In both models, a novel consequence of PTEN expression was to increase Ins(1,3,4,5,6)P5 pool size by 30-40% (p<0.01); this response was wortmannin-insensitive and, therefore, independent of the PtdIns 3-kinase pathway. In U87MG cells, induction of the G129R catalytically inactive PTEN mutant did not affect Ins(1,3,4,5,6)P(5) levels. PTEN induction did not alter the expression of enzymes participating in Ins(1,3,4,5,6)P5 synthesis. Another effect of PTEN expression in U87MG cells was to decrease InsP6 levels by 13% (p<0.02). The InsP6-phosphatase, MIPP, may be responsible for the latter effect; we show that recombinant human MIPP dephosphorylates InsP6 to D/L-Ins(1,2,4,5,6)P5, levels of which increased 60% (p<0.05) following PTEN expression in U87MG cells. Overall, our data add higher inositol phosphates to the list of important cellular regulators [Y. Huang, R.P. Wernyj, D.D. Norton, P. Precht, M.C. Seminario, R.L. Wange, Oncogene, 24 (2005) 3819 ] the levels of which are modulated by expression of the highly pleiotropic PTEN protein.

Operation of a free-electron laser from the extreme ultraviolet to the water window

We report results on the performance of a free-electron laser operating at a wavelength of 13.7 nm where unprecedented peak and average powers for a coherent extreme-ultraviolet radiation source have been measured. In the saturation regime, the peak energy approached 170 J for individual pulses, and the average energy per pulse reached 70 J. The pulse duration was in the region of 10 fs, and peak powers of 10 GW were achieved. At a pulse repetition frequency of 700 pulses per second, the average extreme-ultraviolet power reached 20 mW. The output beam also contained a significant contribution from odd harmonics of approximately 0.6% and 0.03% for the 3rd (4.6 nm) and the 5th (2.75 nm) harmonics, respectively. At 2.75 nm the 5th harmonic of the radiation reaches deep into the water window, a wavelength range that is crucially important for the investigation of biological samples.

Inscribir el declive en el tiempo. Detroit: Auge y crisis de la ciudad industrial

A comienzos del siglo XX, Detroit era una ciudad dinámica en pleno desarrollo. Pronto se convirtió en la cuarta ciudad de Estados Unidos, la capital de la naciente industria automovilística. El crecimiento se prolongó hasta finales de los años 50, cuando, a pesar del auge económico de Estados Unidos y de su área metropolitana, Detroit comenzó a mostrar los primeros signos de estancamiento. La crisis se ha prolongado hasta hoy, cuando Detroit constituye el paradigma de la ciudad industrial en declive. Estas dos imágenes contrapuestas, el auge y la crisis, no parecen explicar por sí mismas las causas de la intensidad y persistencia del declive de Detroit. Analizar las interacciones entre crecimiento económico, políticas públicas locales y desarrollo urbano a lo largo del tiempo permitirá subrayar las continuidades y comprender en qué medida el declive de Detroit ancla sus raíces en el modelo planteado durante la etapa de auge.

Making hay while the sun shines? Socio-economic change, cereal production and climatic deterioration in Early Medieval Ireland

The Early Medieval period in Ireland (c. A.D. 400–1150) has been the subject of much archaeological and historical study. The recent application of various forms of archaeological sciences, as well as palaeoenvironmental studies, to the archaeological record have, however, added fresh impetus to this study area. It seems increasingly evident that significant changes to economy and society occurred during this period and were not recorded in detail in the contemporary documentary sources. This paper will attempt to outline those changes and to assess whether, or to what extent, they were influenced by climate change.

A Simple Triaxial System for Evaluating the Performance of Unsaturated Soils Under Repeated Loading

Unsaturated soils constitute a large proportion of the foundation materials supporting infrastructure throughout the world and they are subject to various loading conditions. This paper describes the development of a simple system for testing unsaturated soils under repeated loading. The equipment was comprised of a modified triaxial cell with hydraulic loading system, hall-effect transducers for on-sample strain measurements, and thermocouple psychrometer for suction measurements. A number of undrained monotonic and repeated loading triaxial tests were performed on compacted samples of kaolin clay in order to attest the newly developed system. The results yielded some useful information on the resilient modulus and permanent deformation of a soil when subjected to repeated loading. There is some difference between the failure deviator stress of samples subjected to repeated and monotonic loading, though repeated loading continued to result in a significant permanent deformation. This paper is aimed at demonstrating the key features of the equipment using preliminary data generated as part of the on-going research.

Effect of genotype on changes in intelligence quotient after dietary relaxation in phenylketonuria and hyperphenylalaninaemia

Background-Associations between genotype and intellectual outcome in patients with phenylketonuria are complicated because intelligence is influenced by many variables, including environmental factors and other genetic determinants. Intellectual changes with age, both on and after relaxation of diet, vary within the patient population. This study aims to determine whether a significant association exists between genotype and change in intelligence after relaxation of diet.

Anti-doping testing at the 2008 European football championship.

Big sports events like the 2008 European Football Championship are a challenge for anti-doping activities, particularly when the sports event is hosted by two different countries and there are two laboratories accredited by the World Anti-Doping Agency. This challenges the logistics of sample collection as well as the chemical analyses, which must be carried out timeously. The following paper discusses the handling of whereabouts information for each athlete and the therapeutic use exemption system, experiences in sample collection and transportation of blood and urine samples, and the results of the chemical analysis in two different accredited laboratories. An overview of the analytical results of blood profiling and growth hormone testing in comparison with the distribution of the normal population is also presented.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Standardization of cytokine flow cytometry assays

Affiliation: Faculté de médecine, Université de Montréal & CANVAC