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Aims This study was designed to investigate the counterbalancing influence of genetic variation in the promoter of the gene encoding P300/CBP associated factor (PCAF), a lysine acetyltransferase (KAT), on coronary heart disease (CHD) and mortality.Methods and results The association of genetic variation in the PCAF-gene with CHD, restenosis and mortality was investigated in three large cohorts. The results were combined to examine overall effects on CHD mortality and on restenosis risk. Compared with the homozygous -2481G allele in the PCAF promoter, a significant reduction in CHD mortality risk with the homozygous -2481C PCAF promoter allele was observed. A combined risk reduction for CHD death for the three studies was 21% (15-26%; p=8.13X10(-4)). In elderly patients (> 58 years) the effects were stronger. Furthermore, this PCAF allele was significantly associated with all-cause mortality (p=0.001). Functional analysis showed that nuclear factors interact in vitro with the oligonucleotides encompassing the -2481G/C polymorphism and that this interaction might be influenced by this polymorphism in the PCAF promoter. Moreover, modulation of PCAF gene expression was detectable upon cuff-placement in an animal model of reactive stenosis.Conclusion We showed in three large prospective studies that the -2481C allele in the PCAF promoter is associated with a significant survival advantage in elderly patients. Our observations promote the concept that epigenetic processes are under genetic control and that, other than environment, variation in genes encoding KATs may also determine susceptibility to CHD outcomes and mortality.

Variation in the NOS3 gene has been related to the development of restenosis. The Glu298Asp polymorphism has previously been investigated for its effect on NO levels and the development of restenosis. However, the variability of findings gave rise to the hypothesis that the functional significance of this polymorphism may only become manifest under conditions of endothelial dysfunction. Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance of NOS3 polymorphisms may depend on the presence of the metabolic syndrome. We examined the impact of the -949 A/G, the -716 C/T and the Glu298Asp polymorphisms in the NOS3 gene on the risk of clinical restenosis in a previously described subpopulation of the GENDER-study, a multicenter prospective study design that enrolled consecutive patients after successful PCI. This subpopulation consisted of 901 patients of whom sufficient data were available to establish absence or presence of the metabolic syndrome. Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined as target vessel revascularization (TVR), was the primary endpoint. We demonstrated that the minor -949G, -716T and 298Asp alleles were associated with a significantly increased risk of TVR in patients with the metabolic syndrome (HR: 1.58 [95% CI: 1.04-2.40], HR: 1.95 [95% CI: 1.02-3.70] and HR: 1.67 [95% CI: 1.09-2.54], respectively). In the group without the metabolic syndrome we observed no association between the three polymorphisms and TVR. We suggest that the metabolic alterations present in patients with the metabolic syndrome influence the functional significance of these polymorphisms and increase the susceptibility of carriers of one of these variations in the NOS3 gene to develop restenosis after PCI.

This work presents the design process, the analysis, and the performance of a cylindrical hollow monopost, made entirely in composites. It is about a translucent structure of height 40m, external diameter 1.60m and the average wall-thickness 11mm. The material is a polymer made up of vinylster resin and reinforced by glass fiber (GFRP). The manufactured processing used is filament winding. Moreover, due to geographical emplacement where it is situated, the structure has to support wind velocity value above 180Km/h and its elastic modulus of the material does not exceed 25GPa. Eventually, we was able to achieve an optimum solution and strentgh structure, considering and developing differents types of approaches and analysis, such as linear, non-linear and buckling.

Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributing factors is the clinical and biological heterogeneity of these still life-threatening diseases, which involve processes that we do not fully understand at the moment. Over the past decades, it has become increasingly clear that part of the gene-environmental interactions relevant for complex diseases is regulated by epigenetic mechanisms such as histone acetylation and DNA methylation. Epigenetic processes modulate gene expression patterns without modifying the actual DNA sequence and have profound effects on the cellular repertoire of expressed genes. They contribute to the expression of genes that play a key role in extracellular matrix formation, inflammation, and proliferation, processes involved in cardiovascular pathologies such as atherosclerosis and restenosis.Therefore, in this review, we argue that epigenetic regulators involved in histone acetylating and deacetylating activities contribute to the pathogenesis of atherosclerosis and restenosis. Furthermore, as alterations in chromatin structure are reversible, these epigenetic modifications are amendable to pharmacological intervention, which may prove to be an effective treatment modality for the management of cardiovascular diseases. © The Author 2009. Chemicals / CAS: 4 n acetyldinaline, 112522-64-2; azelaic acid, 123-99-9; butyric acid, 107-92-6, 156-54-7, 461-55-2; histone, 9062-68-4; histone acetyltransferase, 9054-51-7; histone deacetylase, 9076-57-7; n (2 aminophenyl) 4 [4 (3 pyridinyl) 2 pyrimidinylaminomethyl]benzamide, 726169-73-9, 944537-89-7; oxamflatin, 151720-43-3; panobinostat, 404950-80-7; romidepsin, 128517-07-7; trichostatin A, 58880-19-6; valproic acid, 1069-66-5, 99-66-1; vorinostat, 149647-78-9; Histone Acetyltransferases, 2.3.1.48; Histone Deacetylases, 3.5.1.

Comparative analyses of lipids from fossil plants and from their extant counterparts were undertaken in order to test the taxonomic significance of lipids in palaeobotany. The comparison between lipids from a fossil Ginkgoaceae, Eretmophyllum andegavense, and its extant counterpart, Ginkgo biloba, revealed the presence of original molecules, dimethoxyalkylcoumarins, in lipids from both plants. Such compounds confirm, on chemical grounds the relationship between these extant and fossil Ginkgoaceaes. Moreover, differences in n-alkane distribution between E. andegavense and E. obtusum which are very similar morphologically, confirm that these fossil plants do not belong to the same species. Furthermore, comparative analyses of a fossil Cheirolepidiaceae, Frenelopsis alata, and its extant counterpart, the Cupressaceae Tetraclinis articulata, revealed some similarities between these two species although they do not belong to the same family. Otherwise, comparative analyses of fungi-infected and uninfected samples of F. alata demonstrated that these micro-organisms can significantly affect the chemical composition of fossil plant lipids. In conclusion, even if chemical analyses alone are not sufficient to determine the genus or species of a given fossil plant, they can precise the taxonomy of some specimens that have been previously studied by palaeobotanists.

UMS has developed an industrial power HBT process especially dedicated to power MMICs in the 10GHz frequency range. The process has been qualified and meets the very demanding specifications required for X-Band high power amplifiers. Aside from the obvious RF performances, this includes the demonstration of the necessary stability and reproducibility of the process, associated with state-of-art reliability. It is important to note that the later has been achieved without affecting the high frequency capability of the devices, and demonstrated directly on high power transistors. Thanks to its intrinsic qualities this process can naturally also be used for other applications, like low phase noise voltage controlled oscillators, and power amplifiers at lower frequencies (for mobile phones for instance).

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The comparison of the linearity performance for three PHEMTs have been investigated in Ka band. The studied transistors are a single recessed PHEMT, a double recessed PHEMT and a double recessed dual channel PHEMT. The main result is : at a given output power level, the double recess allows a large improvement of the intermodulation ratio (IMR), thanks to its higher drain-source bias voltage capability, compared to the single recess. The second result is : the double recessed PHEMTs comparison shows that the dual channel, thanks to a more wide and uniform ransconductance distribution than the single channel, is a better solution for linearity application at 26GHz.

The APOS (Advanced Power Subassemblies project addresses the devices (MMIC or discrete) used in the solid state power amplifiers (SSPA) that drive the transmit active antenna. These are key devices and their electrical and thermal performances have a major impact on both the satellite and the ground terminals. GaAs-based heterostructure bipolar transistor, due to their superior power/linearity performance, could be one of these enabling devices. This aspect will be addressed within the frame of this project through three main objectives : 1)To analyse the reliability of UMS HBT technology and demonstrate it meets the requirements of the commercial satellite markets. 2)To improve the power and thermal performances of HBT by developing a power flip- chip assembly technology using thermal bumps in the active area of the power device. 3)To benchmark the developed power HBT technology by using the power MMIC in a suitable active antenna module. This project consortium is formed by Alcatel Space, that will co-ordinate the project, United Monolithic Semiconductors (UMS), Thomson-CSF, Institute for Material Research at Limburg University Centrum (1MO-LUC), DESTIN and Institut d'Electronique et de Microelectronique du Nord (1EMN).

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

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The development of a highly integrated Ka-band (24-26GHz) transceiver module for a high volume point to multipoint telecommunication application is presented. In order to reduce the costs, a full GaAs MMIC solution has been chosen. The module architecture and assembly technology are described. 8 different Ka-band MMICs have been or are being designed and fabricated for this application. The measured performances of the developed MMICs and of the module prototypes are given.