Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung

10.1371/journal.pone.0024019PLoS ONE68

Study of Crystal Growth Kinetics for Mandelic Acid in Water

With the movement by pharmaceutical companies to develop single enantiomers instead of racemic mixtures as drug candidates, the focus of their research interest has turned to problems associated with an efficient preparation or separation of pure enantiomers. Despite the rapid development of enantioselective catalysts for asymmetric synthesis over the past 30 years, very few are really applied in technical scale due to limitations in cost, time for process development and catalyst stability. The resolution of racemates still holds a key position for the production of pure enantiomers. Among other enantioseparation methods, like diastereomeric salt formation and preferential crystallization, enantioseparation can always be performed by crystallization from asymmetric chiral mixtures, where the desired enantiomer is enriched to a certain extent. If this is not resulting from the previous chemical synthesis or production step, the symmetry of racemic mixtures can be broken by a previous resolution step, e. g. by chromatography. Understanding of crystallization kinetics plays an important role for the design and optimization of successful enantioselective crystallization processes. As the final purity of the desired enantiomer is affected by crystal growth, the impact of growth kinetics on the economic potential of this separation process is evident. Furthermore, the influence of the counter enantiomer present in the solution both on crystallization kinetics and product purity is of interest. On this background the work to be presented is concerned with a detailed study on crystal growth kinetics on the example of mandelic acid in water. Based on preceding measurements of thermodynamic data and the metastable zone width in the chiral system [1] experimental data collected during isothermal crystal growth experiments will be shown and analyzed. The studies were performed at different crystallization temperatures and with varying enantiomeric ratio in the initial solution. Growth kinetic data and the applied model are presented and discussed in detail. The influence of the studied parameters on the potential of an efficient enantioselective crystallization process is evaluated. [1] Perlberg, A., H. Lorenz and A. Seidel-Morgenstern Determination of crystallization relevant data for enantioseparation purposes Chemical Engineering Transactions (Volume I) Proceedings of the 15th Int. Symp. on Industrial Crystallization, (Ed.) A. Chianese, pp. 173-178, AIDIC, Sorrento, Italy 200

Nouvelles structures pour lasers à impulsions brèves de forte puissance (conception et réalisation d'amplificateurs/lasers guides d'onde élaborés par épitaxie en phase liquide et démonstration de lasers femtoseconde en Y2SiO5 : Yb et Lu2SiO5 : Yb)

Les orthosilicates d'yttrium et de lutétium dopés Yb3+, de formules respectives Y2SiO5:Yb et Lu2SiO5:Yb, possèdent des caractéristiques spectroscopiques favorables à un fonctionnement efficace en régime laser continu et femtoseconde de forte puissance. Leur première démonstration de fonctionnement en régime femtoseconde a fourni des performances exceptionnelles en terme d efficacité et de puissance de sortie. Afin de réaliser des sources lasers solides compactes et efficaces à partir de ces matériaux, nous avons choisi de privilégier une approche incluant un milieu actif à géométrie de guide d'onde plan, réalisé par épitaxie en phase liquide, pompé par la face supérieure par une barrette de diodes laser. La croissance de couches de Y2SiO5:Yb fortement dopées, de compositions et d épaisseurs variées a été démontrée. L accroissement d indice lié à la substitution des différents dopants est analysé. Les caractéristiques spectroscopiques des couches sont semblables à celles du matériau massif, avec une qualité cristalline sensiblement supérieure. L évolution du temps de vie de l ion Yb en fonction du dopage affiche notamment une croissance particulièrement douce, preuve d une faible concentration en centres pièges extrinsèques. Les guides d ondes YSO:24%Yb présentent des pertes en propagation inférieures à 0.3dB/cm, et ont démontré une amplification de 2.9dB/cm à 1082nm avec un faisceau de sortie monomode. La réalisation des premiers lasers guides d onde monolithiques en YSO:Yb a aussi été démontrée. Ils ont fourni une puissance de sortie de 340mW à 1082nm, avec une efficacité de 14%, pour un coupleur de sortie de 4%.Yb-doped yttrium and lutetium orthosilicates, Y2SiO5:Yb and Lu2SiO5:Yb respectively, exhibit spectroscopic properties favorable to an efficient laser operation in both high power cw and femtosecond regime. Their first diode-pumped femtosecond operation demonstration lead to exceptional performances in terms of output power and efficiency. In order to realize compact and efficient solid-state laser devices using those materials, we chose a configuration with an Yb-doped medium planar waveguide geometry, grown by liquid phase epitaxy, face-pumped by a single laser diode bar. The growth of highly doped Y2SiO5:Yb layers, within a large range of compositions and thicknesses, was demonstrated. The refractive index increase due to the substitution of the various dopants is analyzed. The layers spectroscopic properties are similar to the bulk ones, with an noticeably higher crystalline quality. The Yb ion lifetime evolution with respect to its doping shows up a particularly low decrease, proof of a low concentration of extrinsic quenching centers. The covered YSO:24%Yb waveguides exhibit lower than 0.3dB/cm propagation losses, and provided up to 2.9dB/cm net amplification at 1082nm with a single mode output. The realization of the first diode-pumped monolithic cw waveguide lasers was also demonstrated. For a 4% output coupler, they provided up to 340mW at 1082nm with a 14% slope efficiency.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF