Theory of Melting and the Optical Properties of Gold/DNA Nanocomposites

We describe a simple model for the melting and optical properties of a DNA/gold nanoparticle aggregate. The optical properties at fixed wavelength change dramatically at the melting transition, which is found to be higher and narrower in temperature for larger particles, and much sharper than that of an isolated DNA link. All these features are in agreement with available experiments. The aggregate is modeled as a cluster of gold nanoparticles on a periodic lattice connected by DNA bonds, and the extinction coefficient is computed using the discrete dipole approximation. Melting takes place as an increasing number of these bonds break with increasing temperature. The melting temperature corresponds approximately to the bond percolation threshold.Comment: 5 pages, 4 figure. To be published in Phys. Rev.

Classical and Quantum Strings in compactified pp-waves and Godel type Universes

We consider Neveu-Schwarz pp-waves with spacetime supersymmetry. Upon compactification of a spacelike direction, these backgrounds develop Closed Null Curves (CNCs) and Closed Timelike Curves (CTCs), and are U-dual to supersymmetric Godel type universes. We study classical and quantum strings in this background, with emphasis on the strings winding around the compact direction. We consider two types of strings: long strings stabilized by NS flux and rotating strings which are stabilized against collapse by angular momentum. Some of the latter strings wrap around CNCs and CTCs, and are thus a potential source of pathology. We analyze the partition function, and in particular discuss the effects of these string states. Although our results are not conclusive, the partition function seems to be dramatically altered due to the presence of CNCs and CTCs. We discuss some interpretations of our results, including a possible sign of unitary violation.Comment: 42 pages, LaTeX, 2 figure

Structure Formation, Melting, and the Optical Properties of Gold/DNA Nanocomposites: Effects of Relaxation Time

We present a model for structure formation, melting, and optical properties of gold/DNA nanocomposites. These composites consist of a collection of gold nanoparticles (of radius 50 nm or less) which are bound together by links made up of DNA strands. In our structural model, the nanocomposite forms from a series of Monte Carlo steps, each involving reaction-limited cluster-cluster aggregation (RLCA) followed by dehybridization of the DNA links. These links form with a probability $p_{eff}$ which depends on temperature and particle radius $a$. The final structure depends on the number of monomers (i. e. gold nanoparticles) $N_m$, $T$, and the relaxation time. At low temperature, the model results in an RLCA cluster. But after a long enough relaxation time, the nanocomposite reduces to a compact, non-fractal cluster. We calculate the optical properties of the resulting aggregates using the Discrete Dipole Approximation. Despite the restructuring, the melting transition (as seen in the extinction coefficient at wavelength 520 nm) remains sharp, and the melting temperature $T_M$ increases with increasing $a$ as found in our previous percolation model. However, restructuring increases the corresponding link fraction at melting to a value well above the percolation threshold. Our calculated extinction cross section agrees qualitatively with experiments on gold/DNA composites. It also shows a characteristic ``rebound effect,'' resulting from incomplete relaxation, which has also been seen in some experiments. We discuss briefly how our results relate to a possible sol-gel transition in these aggregates.Comment: 12 pages, 10 figure

Killing spectroscopy of closed timelike curves

We analyse the existence of closed timelike curves in spacetimes which possess an isometry. In particular we check which discrete quotients of such spaces lead to closed timelike curves. As a by-product of our analysis, we prove that the notion of existence or non-existence of closed timelike curves is a T-duality invariant notion, whenever the direction along which we apply such transformations is everywhere spacelike. Our formalism is straightforwardly applied to supersymmetric theories. We provide some new examples in the context of D-branes and generalized pp-waves.Comment: 1+35 pages, no figures; v2, new references added. Final version to appear in JHE

Gene signature for risk stratification and treatment of breast cancer: Incorporating tumor biology in clinical decision-making

The aim of this thesis is to evaluate outcome prediction and clinical relevance of the 70-gene signature for locoregional and distant recurrence, its influence on risk assessment and adjuvant systemic therapy (AST) recommendations, and its additional value to established clinical guidelines used in breast cancer treatment. In addition, we used the 70-gene signature to gain better insight in the biological background of tumors detected in a population-based screening program

Tumor heterogeneity impairs robustness of Ki67 scoring in breast cancer

Immunology and molecular genetics of gynecological cancer

Risk estimations and treatment decisions in early stage breast cancer: Agreement among oncologists and the impact of the 70-gene signature

Contains fulltext : 136740.pdf (publisher's version ) (Open Access)BACKGROUND: Clinical decision-making in patients with early stage breast cancer requires adequate risk estimation by medical oncologists. This survey evaluates the agreement among oncologists on risk estimations and adjuvant systemic treatment (AST) decisions and the impact of adding the 70-gene signature to known clinico-pathological factors. METHODS: Twelve medical oncologists assessed 37 breast cancer cases (cT1-3N0M0) and estimated their risk of recurrence (high or low) and gave a recommendation for AST. Cases were presented in two written questionnaires sent 4weeks apart. Only the second questionnaire included the 70-gene signature result. RESULTS: The level of agreement among oncologists in risk estimation (kappa=0.57) and AST recommendation (kappa=0.57) was 'moderate' in the first questionnaire. Adding the 70-gene signature result significantly increased the agreement in risk estimation to 'substantial' (kappa=0.61), while agreement in AST recommendations remained 'moderate' (kappa=0.56). Overall, the proportion of high risk was reduced with 7.4% (range: 6.9-22.9%; p<0.001) and the proportion of chemotherapy that was recommended was reduced with 12.2% (range: 5.4-29.5%; p<0.001). CONCLUSION: Oncologists' risk estimations and AST recommendations vary greatly. Even though the number of participating oncologists is low, our results underline the need for a better standardisation tool in clinical decision-making, in which integration of the 70-gene signature may be helpful in certain subgroups to provide patients with individualised, but standardised treatment

Prospective cost-effectiveness analysis of genomic profiling in breast cancer

Background: The cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates. Methods: Costs and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N−) patients included in the RASTER study (n = 427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10–30 mm, grade II, age 40–70; (2) ductal, oestrogen receptor-positive, tumour diameter 5–30 mm, grade II/III and age 40–70. Results: Based on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature. Conclusions: The use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective