Boosting the concordance index for survival data - a unified framework to derive and evaluate biomarker combinations

The development of molecular signatures for the prediction of time-to-event outcomes is a methodologically challenging task in bioinformatics and biostatistics. Although there are numerous approaches for the derivation of marker combinations and their evaluation, the underlying methodology often suffers from the problem that different optimization criteria are mixed during the feature selection, estimation and evaluation steps. This might result in marker combinations that are only suboptimal regarding the evaluation criterion of interest. To address this issue, we propose a unified framework to derive and evaluate biomarker combinations. Our approach is based on the concordance index for time-to-event data, which is a non-parametric measure to quantify the discrimatory power of a prediction rule. Specifically, we propose a component-wise boosting algorithm that results in linear biomarker combinations that are optimal with respect to a smoothed version of the concordance index. We investigate the performance of our algorithm in a large-scale simulation study and in two molecular data sets for the prediction of survival in breast cancer patients. Our numerical results show that the new approach is not only methodologically sound but can also lead to a higher discriminatory power than traditional approaches for the derivation of gene signatures.Comment: revised manuscript - added simulation study, additional result

Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase 2 (IKK2, IKK-beta, IKBKB) and TRAF2 indicating a dose dependent regulatory function of TRAF1 for NF-kappa B signaling

IKK2 is one of the most crucial signaling kinases for activation of the transcription factor NF-kappa B. Since many NF-kappa B activating pathways converge at the level of IKK2, we searched for interaction partners of this kinase using the C-terminal part (aa 466-756) as bait in a yeast two-hybrid system. We identified the N-terminal part (aa 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner, which was subsequently confirmed in mammalian cells by coimmunoprecipitation experiments. However, this interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling indicating that relative levels of IKK2, TRAF1 and TRAF2 might be important for the final biological readout. Reporter gene and kinase assays using ectopic expression of TRAF1 indicated that it can have both activating and inhibiting functions for IKK2 and NF-kappa B. Co-expression of fluorescently tagged TRAF1 and TRAF2 at different ratios implied that TRAF1 can affect clustering and presumably the activating function of TRAF2 in a dose dependent manner

Organic Farming and Climate Change

This publication concludes that organic agriculture has much to offer in both mitigation of climate change through its emphasis on closed nutrient cycles and is a particularly resilient and productive system for adaptation strategies. It also raises the issue of whether organic agriculture should be eligible for carbon credits under voluntary carbon offsetting markets and the Clean Development Mechanism

Do individuals recognize cascade behavior of others? An Experimental Study

In an information cascade experiment participants are confronted with artificial predecessors predicting in line with the BHW model (Bikchandani et al., 1992). Using the BDM (Becker et al., 1964) mechanism we study participants' probability perceptions based on maximum prices for participating in the prediction game. We find increasing maximum prices the more coinciding predictions of predecessors are observed, regardless of whether additional information is revealed by these predictions. Individual price patterns of more than two thirds of the participants indicate that cascade behavior of predecessors is not recognized

Molecular recognition in a lattice model: An enumeration study

We investigate the mechanisms underlying selective molecular recognition of single heteropolymers at chemically structured planar surfaces. To this end, we study systems with two-letter (HP) lattice heteropolymers by exact enumeration techniques. Selectivity for a particular surface is defined by an adsorption energy criterium. We analyze the distributions of selective sequences and the role of mutations. A particularly important factor for molecular recognition is the small-scale structure on the polymers.Comment: revised version with additional plot

HST observations of the limb polarization of Titan

Titan is an excellent test case for detailed studies of the scattering polarization from thick hazy atmospheres. We present the first limb polarization measurements of Titan, which are compared as a test to our limb polarization models. Previously unpublished imaging polarimetry from the HST archive is presented which resolves the disk of Titan. We determine flux-weighted averages of the limb polarization and radial limb polarization profiles, and investigate the degradation and cancelation effects in the polarization signal due to the limited spatial resolution of our observations. Taking this into account we derive corrected values for the limb polarization in Titan. The results are compared with limb polarization models, using atmosphere and haze scattering parameters from the literature. In the wavelength bands between 250 nm and 2000 nm a strong limb polarization of about 2-7 % is detected with a position angle perpendicular to the limb. The fractional polarization is highest around 1 micron. As a first approximation, the polarization seems to be equally strong along the entire limb. The detected polarization is compatible with expectations from previous polarimetric observations taken with Voyager 2, Pioneer 11, and the Huygens probe. Our results indicate that ground-based monitoring measurements of the limb-polarization of Titan could be useful for investigating local haze properties and the impact of short-term and seasonal variations of the hazy atmosphere of Titan. Planets with hazy atmospheres similar to Titan are particularly good candidates for detection with the polarimetric mode of the upcoming planet finder instrument at the VLT. Therefore, a good knowledge of the polarization properties of Titan is also important for the search and investigation of extra-solar planets.Comment: 13 pages, 13 figures, accepted for publication in Astronomy & Astrophysic

Measurement of the earthshine polarization in the B, V, R, and I band as function of phase

The characterization of the polarimetric properties of the planet Earth is important for the interpretation of expected observations and the planning of future instruments. We present a multi-wavelengths and multi-phase set of benchmark values for the polarization signal of the integrated light from the planet Earth derived from new polarimetric observations of the earthshine back-scattered from the Moon's dark side. Using a new, specially designed wide field polarimeter we measured the fractional polarization of the earthshine in the B, V, R and I filters for Earth phase angles alpha between 30{\deg} and 110{\deg}. The phase dependence of the earthshine polarization is fitted by a function p x sin(alpha)^2. To determine the polarization of the planet Earth we correct our earthshine measurements by a polarization efficiency function for the lunar surface derived from measurements of lunar samples from the literature. The polarization of the earthshine decreases towards longer wavelengths and is about a factor 1.3 lower for the higher albedo highlands. For mare regions the measured maximum polarization is about 13 % at quadrature in the B band. The resulting fractional polarizations for Earth are 24.6 % for the B band, 19.1 % for the V band, 13.5 % for the R band, and 8.3 % for the I band. Together with literature values for the spectral reflectivity of Earth we obtain a contrast between the polarized flux of the Earth and the (total) flux of the Sun with an uncertainty of less than 20 % and we find that the best phase to detect an Earth twin is around an Earth phase alpha=65{\deg}. The polarimetric models of Earth-like planets from Stam (2008) are in qualitative agreement with our results but there are also significant differences which might guide more detailed computations.Comment: 14 pages, 14 figures, accepted for publication in Astronomy & Astrophysic