The conformation of cylindrical brush polymers with a polymethacrylate main and polystyrene side chains (6 e P n sc e 33, with P n sc the number-average degree of polymerization of the side chains) were studied by combined light and small-angle neutron scattering experiments. The results reveal that the main chain stiffness expressed in terms of the Kuhn statistical segment length, l k , increases with side chain length but does not follow scaling predictions which most probably is due to the limited length of the side chains investigated experimentally. In this respect the present work addresses the transition regime from flexible coils to stiff cylindrical brushes as a function of side chain length. In detail, the increase of l k is stronger in toluene, a very good solvent for the side chains, than in the poor solvent cyclohexane and does not level off for the longest side chains investigated (P n sc ) 33). In contrast to earlier work, the cylinder length per main chain monomer is found to be independent of side chain length but to depend slightly on the solvent quality, i.e., l m ) 0.241 nm in toluene and l m ) 0.207 nm in cyclohexane. The value determined in toluene is close to the maximum value of l m ) 0.25 nm expected for a fully stretched vinylic main chain, whereas the smaller value for l m in cyclohexane suggests a local coiling of the main chain, most probably caused by less repulsive interactions between the side chains. The discrepancy to some earlier scattering experiments could be resolved, but the origin of frequently reported much smaller cylinder lengths derived by atomic force microscopy remains unclear.

The synthesis and structural analysis of a library containing 13 taper- and conical-shaped self-assembling dendrons, 16 dendritic monomers, and their corresponding polymers is reported. Fifteen of these polymers exhibit a well-defined cylindrical shape produced by the self-assembly of their dendritic side groups that self-organizes in a hexagonal columnar two-dimensional liquid crystalline lattice. The retrosynthetic analysis of this lattice by X-ray diffraction (XRD) showed that the diameter (60 to 41 Å) and the number of repeat units forming the cylinder cross-section (7 to 1.9) of these polymers are determined by the structure of their dendritic side groups. This demonstrates that, in the hexagonal columnar lattice, the conformation (from helical to fully extended) and the stiffness of the polymer backbone penetrating through the center of the cylinder are controlled in a systematic and predictive way by the structure of the side groups. Dynamic and static light-scattering experiments have demonstrated the same trend for the stiffness of these polymers in solution (Kuhn segment length from 200 to 1032 Å). Single chains and monolayers of these polymers were visualized and quantitatively analyzed by scanning force microscopy (SFM) on a graphite surface to provide the first comparative study of the conformation, stiffness, and contour length in solution (by light scattering), in the disordered solid state on a flat substrate (by SFM), and in the hexagonal columnar lattice (by XRD). The elaboration of this library of visualizable cylindrical macromolecules with controlled chain conformation and stiffness accesses the elucidation of many fundamental problems of the field of polymer science at the molecular level and the design of multifunctional nanoscale systems based on single polymer chains.

HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.

We have investigated the swelling of a polystyrene brush in cyclohexane at varying temperatures with angle-dependent ellipsometry. The brush was grown in situ on the base of a high index prism by the "grafting from" technique. In the dry state it has a thickness of d ) 134 nm. At the θ temperature it swells to about 600 nm. In accordance with the predictions from mean field theory, the brush thickness continuously increases with solvent quality. As the thickness increases, the shape of the segment density profile becomes smoother with a broad dilute transition region between the brush and the solvent.

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GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.

High proliferation rates are characteristic of cancer, and proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. Based on prior data on differences in molecular subgroups of breast cancer, we hypothesized that the significance of single proliferation markers might differ in luminal, Her2-positive and triple-negative subtypes. Therefore, we compared mRNA expression data of Ki67, TOP2A, and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer samples. "Luminal," "triple-negative," and "Her2-positive" subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs. The analysis of the three potential proliferation markers revealed subtype-specific differences: in luminal carcinomas, expression of all three markers was a significant indictor of early recurrence in univariate and multivariate analysis, but RacGAP1 was superior to Ki67 and TOP2A in significance. In triple-negative tumors, only Ki67 was a significant and independent marker, whereas none of the markers showed a significant prognostic impact in Her2-positive cases. Within the group of luminal carcinomas, the proliferation markers had different impact depending on the treatment of patients: in untreated patients, Ki67, TOP2A, and RacGAP1 were significant and independent prognostic markers. In chemotherapy-treated patients, overexpression of all three markers was predictive for early recurrence, but only RacGAP1 retained significance in multivariate analysis. In contrast, RacGAP1 was the only predictive proliferation marker in the endocrine treatment group. These data point to subtype-specific differences in the relevance of proliferation-associated genes, and RacGAP1 might be a strong prognostic and predictive marker in the luminal subgroup.

BackgroundThe number of unintentionally childless couples is increasing as more couples seek to conceive for the first time in the third or fourth decade of the woman’s life. Determination of ovarian reserve is an essential component of infertility assessment. The Anti-Müllerian-Hormone (AMH) seems to be the most reliable predictor of ovarian reserve. In this study we analyzed AMH in a cohort of pregnant women without fertility impairment to determine age-dependent decline and possible AMH fluctuations during pregnancy and postpartum.MethodsA total of 554 healthy women aged 16 to 47 years without history of infertility or previous surgery on the ovaries were enrolled in the study between 1995 and 2012. In 450 women, a single measurement of AMH was taken during pregnancy, allowing for cross sectional analysis of trimester- and age-related differences in AMH levels. For another 15 women longitudinal data on AMH levels for all trimesters was recorded. In addition, for 69 women AMH was measured at the time just before and after delivery, and for another 20 AMH was measured just before delivery and once on each of the first four days after delivery. We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. Non-parametric statistical tests were used to compare AMH levels between age groups, trimesters and postpartum.ResultsComparison between the trimesters revealed a significant difference in AMH values at each trimester (first trimester: 1.69 ng/ml (IQR 0.71–3.10), second trimester: 0.8 ng/ml (IQR 0.48–1.41), third trimester: 0.5 ng/ml (IQR 0.18–1.00)). AMH significantly dropped during the course of pregnancy and immediately after delivery, whereas an increase was observed over the first four days postpartum. Women, greater than or equal to 35 years, showed significant lower AMH levels than those <35 years across all trimesters.ConclusionsAMH levels decrease during pregnancy. The decline in AMH levels during pregnancy indicates ovarian suppression. AMH levels recover quickly after delivery. AMH levels assessed in pregnant women are not an accurate indicator of ovarian reserve, since AMH levels during pregnancy seem not to be independent of gestational age.