Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data

The current standard therapies for advanced, recurrent or metastatic colon cancer are the 5-fluorouracil and oxaliplatin or irinotecan schedules (FOxFI) +/− targeted drugs cetuximab or bevacizumab. Treatment with the FOxFI cytotoxic chemotherapy regimens causes significant toxicity and might induce secondary cancers. The overall low efficacy of the targeted drugs seen in colon cancer patients still is hindering the substitution of the chemotherapy. The ONCOTRACK project developed a strategy to identify predictive biomarkers based on a systems biology approach, using omics technologies to identify signatures for personalized treatment based on single drug response data. Here, we describe a follow-up project focusing on target-specific drug combinations. Back- ground for this experimental preclinical study was that, by analyzing the tumor growth inhibition in the PDX models by cetuximab treatment, a broad heterogenic response from complete regression to tumor growth stimulation was observed. To provide confirmation of the hypothesis that drug combinations blocking alternatively activated oncogenic pathways may improve therapy outcomes, 25 models out of the well-characterized ONCOTRACK PDX panel were subjected to treatment with a drug combination scheme using four approved, targeted cancer drugs

Real-Time-RG Analysis of the Dynamics of the Spin-Boson Model

Using a real-time renormalization group method we determine the complete dynamics of the spin-boson model with ohmic dissipation for coupling strengths $\alpha\lesssim 0.1-0.2$. We calculate the relaxation and dephasing time, the static susceptibility and correlation functions. Our results are consistent with quantum Monte Carlo simulations and the Shiba relation. We present for the first time reliable results for finite cutoff and finite bias in a regime where perturbation theory in $\alpha$ or in tunneling breaks down. Furthermore, an unambigious comparism to results from the Kondo model is achieved.Comment: 4 pages, 5 figures, 1 tabl

Tunneling broadening of vibrational sidebands in molecular transistors

Transport through molecular quantum dots coupled to a single vibration mode is studied in the case with strong coupling to the leads. We use an expansion in the correlation between electrons on the molecule and electrons in the leads and show that the tunneling broadening is strongly suppressed by the combination of the Pauli principle and the quantization of the oscillator. As a consequence the first Frank-Condon step is sharper than the higher order ones, and its width, when compared to the bare tunneling strength, is reduced by the overlap between the groundstates of the displaced and the non-displaced oscillator.Comment: 8 pages, 3 figures. PRB, in pres

Anti-Kaon Induced Reactions on the Nucleon

Using a previously established effective Lagrangian model we describe anti-kaon induced reactions on the nucleon. The dominantly contributing channels in the cm-energy region from threshold up to 1.72 GeV are included (K N, \pi \Sigma, \pi \Lambda). We solve the Bethe-Salpeter equation in an unitary $K$-matrix approximation.Comment: 21 pages, 13 figures, minor typos corrected, accepted for publication in Phys. Rev.

Turning Points in the Evolution of Isolated Neutron Stars' Magnetic Fields

During the life of isolated neutron stars (NSs) their magnetic field passes through a variety of evolutionary phases. Depending on its strength and structure and on the physical state of the NS (e.g. cooling, rotation), the field looks qualitatively and quantitatively different after each of these phases. Three of them, the phase of MHD instabilities immediately after NS's birth, the phase of fallback which may take place hours to months after NS's birth, and the phase when strong temperature gradients may drive thermoelectric instabilities, are concentrated in a period lasting from the end of the proto--NS phase until 100, perhaps 1000 years, when the NS has become almost isothermal. The further evolution of the magnetic field proceeds in general inconspicuous since the star is in isolation. However, as soon as the product of Larmor frequency and electron relaxation time, the so-called magnetization parameter, locally and/or temporally considerably exceeds unity, phases, also unstable ones, of dramatic changes of the field structure and magnitude can appear. An overview is given about that field evolution phases, the outcome of which makes a qualitative decision regarding the further evolution of the magnetic field and its host NS.Comment: References updated, typos correcte

Ambient particulate pollution and the world-wide prevalence of asthma, rhinoconjunctivitis and eczema in children: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC)

Objectives: To investigate the effect of ambient particulate matter on variation in childhood prevalence of asthma, rhinoconjunctivitis and eczema. Methods: Prevalences of asthma, rhinoconjunctivitis and eczema obtained in Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) were matched with city-level estimates of residential PM10 obtained from a World Bank model. Associations were investigated using binomial regression adjusting for GNP per capita and for clustering within country. For countries with more than one centre, a two stage meta-analysis was carried out. The results were compared with a meta-analysis of published multi-centre studies. Results: Annual concentrations of PM₁₀ at city level were obtained for 105 ISAAC centres in 51 countries. After controlling for GNP per capita, there was a weak negative association between PM₁₀ and various outcomes. For severe wheeze in 13-14-year-olds, the OR for a 10 μg/m³ increase in PM₁₀ was 0.92 (95 CI 0.84 to 1.00). In 24 countries with more than one centre, most summary estimates for within-country associations were weakly positive. For severe wheeze in 13-14-year-olds, the summary OR for a 10 μg/m³ increase in PM₁₀ was 1.01 (0.92 to 1.10). This result was close to a summary OR of 0.99 (0.91 to 1.06) obtained from published multi-centre studies. Conclusions: Modelled estimates of particulate matter at city level are imprecise and incomplete estimates of personal exposure to ambient air pollutants. Nevertheless, our results together with those of previous multi-centre studies, suggest that urban background PM₁₀ has little or no association with the prevalence of childhood asthma, rhinoconjunctivitis or eczema either within or between countries

ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): ASL pipeline inventory

Purpose: To create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly available pipelines to guide novice ASL users in selecting their optimal pipeline. Methods: Developers self-assessed their pipelines using a questionnaire developed by the Task Force 1.1 of the ISMRM Open Science Initiative for Perfusion Imaging. Additionally, each publicly available pipeline was evaluated by two independent testers with basic ASL experience using a scoring system created for this purpose. Results: The developers of 21 pipelines filled the questionnaire. Most pipelines are free for noncommercial use (n = 18) and work with the standard NIfTI (Neuroimaging Informatics Technology Initiative) data format (n = 15). All pipelines can process standard 3D single postlabeling delay pseudo-continuous ASL images and primarily differ in their support of advanced sequences and features. The publicly available pipelines (n = 9) were included in the independent testing, all of them being free for noncommercial use. The pipelines, in general, provided a trade-off between ease of use and flexibility for configuring advanced processing options. Conclusion: Although most ASL pipelines can process the common ASL data types, only some (namely, ASLPrep, ASLtbx, BASIL/Quantiphyse, ExploreASL, and MRICloud) are well-documented, publicly available, support multiple ASL types, have a user-friendly interface, and can provide a useful starting point for ASL processing. The choice of an optimal pipeline should be driven by specific data to be processed and user experience, and can be guided by the information provided in this ASL inventory

WγγW\gamma\gamma Production at the Fermilab Tevatron Collider: Gauge Invariance and Radiation Amplitude Zero

The electroweak process $p\bar p \to \ell^\pm\nu\gamma\gamma$ is calculated at tree level, including finite W width effects. In order to obtain a gauge invariant amplitude, the imaginary parts of $WW\gamma$ triangle graphs and $WW\gamma\gamma$ box diagrams have to be included, in addition to resumming the imaginary contributions to the W polarization. We demonstrate the existence of a radiation amplitude zero in $p\bar p \to W^\pm \gamma\gamma \to \ell^\pm\nu\gamma\gamma$, and discuss how it may be observed in correlations of the $\gamma\gamma$ and lepton rapidities at the Fermilab Tevatron.Comment: 37 pages,12 figures, postscript file also available via anonymous ftp at ftp://ucdhep.ucdavis.edu/han/vvv/Wgmgm.p

Nonequilibrium Weak Processes in Kaon Condensation I --- Reaction rate for the thermal kaon process ---

We investigate the thermal kaon process,in which kaons are thermally produced via nucleon-nucleon collisions.This process is relevant to nonequilibrium dynamics of kaon condensation inside neutron stars.The reaction rates for these processes are calculated, and their temperature and density dependences are compared with those of other reaction rates.It is shown that the thermal kaon process is dominant over other relevant weak reactions throughout the nonequilibrium process, such as the kaon-induced Urca and the modified Urca reactions, and may control the entire evolution of the kaon condensate. The characteristic role of the soft and hard kaons during the evolution is explained, and implications for astrophysical phenomena are briefly discussed.Comment: 31 pages,incl.10 eps figures,RevTe

S=−1S=-1 Meson-Baryon Unitarized Coupled Channel Chiral Perturbation Theory and the S01−S_{01}- Λ\Lambda(1405) and −Λ- \Lambda(1670) Resonances

The $s-$wave meson-baryon scattering is analyzed for the strangeness $S=-1$ and isospin I=0 sector in a Bethe-Salpeter coupled channel formalism incorporating Chiral Symmetry. Four channels have been considered: $\pi \Sigma$, $\bar K N$, $\eta \Lambda$ and $K \Xi$. The required input to solve the Bethe-Salpeter equation is taken from lowest order Chiral Perturbation Theory in a relativistic formalism. There appear undetermined low energy constants, as a consequence of the renormalization of the amplitudes, which are obtained from fits to the $\pi\Sigma\to\pi\Sigma$ mass-spectrum, to the elastic $\bar K N \to \bar K N$ and $\bar K N\to \pi \Sigma$ $t$--matrices and to the $K^- p \to \eta \Lambda$ cross section data. The position and residues of the complex poles in the second Riemann Sheet of the scattering amplitude determine masses, widths and branching ratios of the $S_{01}-$ $\Lambda$(1405) and $-\Lambda$(1670) resonances, in reasonable agreement with experiment. A good overall description of data, from $\pi \Sigma$ threshold up to 1.75 GeV, is achieved despite the fact that three-body channels have not been explicitly included.Comment: 23 pages, Latex, 10 Figures. In this revised version a new subsection 3.6 on Heavy Baryon Expansion and new references have been adde