Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer predicting the response to second-line hormone or chemotherapy

Concentrations of soluble c-erbB-2 were determined in the sera of 64 patients with distant metastasis from advanced breast cancer receiving second-line hormone or chemotherapy in comparison to 35 breast cancer patients without detectable recurrent disease and 17 healthy blood donors. The sera of non-metastatic breast cancer patients contained s-erbB-2 concentrations similar to those of healthy blood donors. Patients with distant metastasis from advanced breast cancer had significantly higher values of s-erbB-2 in comparison to patients with non-disseminated disease (mean: 59.6 vs. 11.6 U/ml; p = 0.022). A significant correlation was observed between s-erbB-2 serum levels and serum LDH concentrations (p < 0.001), levels of alkaline phosphatase (p < 0.001), and the presence of hepatic metastasis (p = 0.001). Time to tumor progression was significantly shorter in patients with s-erbB-2 levels above 40 U/ml (mean: 23.4 vs. 56.7 months; p = 0.002). Furthermore, breast cancer patients with hepatic metastasis and those with elevated s-erbB-2 serum levels above 40 U/ml had limited response to hormone or chemotherapy. Non-responders had significantly higher s-erbB-2 levels (mean: 270.3, range: 42-500 U/ml;) compared with the responder group (mean: 23.1, range: 0-149 U/ml; p < 0.001). Logistic regression analysis indicated that elevated s-erbB-2 serum levels above 40 U/ml independently predicted an unfavorable response to second-line hormone or chemotherapy in patients with advanced metastatic breast cancer. Copyright (C) 2002 S. KargerAG, Basel

Interaction-induced charge and spin pumping through a quantum dot at finite bias

We investigate charge and spin transport through an adiabatically driven, strongly interacting quantum dot weakly coupled to two metallic contacts with finite bias voltage. Within a kinetic equation approach, we identify coefficients of response to the time-dependent external driving and relate these to the concepts of charge and spin emissivities previously discussed within the time-dependent scattering matrix approach. Expressed in terms of auxiliary vector fields, the response coefficients allow for a straightforward analysis of recently predicted interaction-induced pumping under periodic modulation of the gate and bias voltage [Phys. Rev. Lett. 104, 226803 (2010)]. We perform a detailed study of this effect and the related adiabatic Coulomb blockade spectroscopy, and, in particular, extend it to spin pumping. Analytic formulas for the pumped charge and spin in the regimes of small and large driving amplitude are provided for arbitrary bias. In the absence of a magnetic field, we obtain a striking, simple relation between the pumped charge at zero bias and at bias equal to the Coulomb charging energy. At finite magnetic field, there is a possibility to have interaction-induced pure spin pumping at this finite bias value, and generally, additional features appear in the pumped charge. For large-amplitude adiabatic driving, the magnitude of both the pumped charge and spin at the various resonances saturate at values which are independent of the specific shape of the pumping cycle. Each of these values provide an independent, quantitative measurement of the junction asymmetry.Comment: 17 pages, 8 figure

Low temperature acoustic properties of amorphous silica and the Tunneling Model

Internal friction and speed of sound of a-SiO(2) was measured above 6 mK using a torsional oscillator at 90 kHz, controlling for thermal decoupling, non-linear effects, and clamping losses. Strain amplitudes e(A) = 10^{-8} mark the transition between the linear and non-linear regime. In the linear regime, excellent agreement with the Tunneling Model was observed for both the internal friction and speed of sound, with a cut-off energy of E(min) = 6.6 mK. In the non-linear regime, two different behaviors were observed. Above 10 mK the behavior was typical for non-linear harmonic oscillators, while below 10 mK a different behavior was found. Its origin is not understood.Comment: 1 tex file, 6 figure

A Microfluidic Device for Kinetic Optimization of Protein Crystallization and In Situ Structure Determination

The unprecedented economies of scale and unique mass transport properties of microfluidic devices made them viable nano-volume protein crystallization screening platforms. However, realizing the full potential of microfluidic crystallization requires complementary technologies for crystal optimization and harvesting. In this paper, we report a microfluidic device which provides a link between chip-based nanoliter volume crystallization screening and structure analysis through “kinetic optimization” of crystallization reactions and in situ structure determination. Kinetic optimization through systematic variation of reactor geometry and actuation of micromechanical valves is used to screen a large ensemble of kinetic trajectories that are not practical with conventional techniques. Using this device, we demonstrate control over crystal quality, reliable scale-up from nanoliter volume reactions, facile harvesting and cryoprotectant screening, and protein structure determination at atomic resolution from data collected in-chip

Lattice-mismatch-induced granularity in CoPt-NbN and NbN-CoPt superconductor-ferromagnet heterostructures: Effect of strain

The effect of strain due to lattice mismatch and of ferromagnetic (FM) exchange field on superconductivity (SC) in NbN-CoPt bilayers is investigated. Two different bilayer systems with reversed deposition sequence are grown on MgO (001) single crystals. While robust superconductivity with high critical temperature (T_c ~ 15.3 K) and narrow transition width DelT_c ~ 0.4 K) is seen in two types of CoPt-NbN/MgO heterostructures where the magnetic anisotropy of CoPt is in-plane in one case and out-of-plane in the other, the NbN-CoPt/MgO system shows markedly suppressed SC response. The reduced SC order parameter of this system, which manifests itself in Tc, temperature dependence of critical current density J_c (T), and angular (Phi) variation of flux-flow resistivity Rho_f is shown to be a signature of the structure of NbN film and not a result of the exchange field of CoPt. The Rho_f (H,T,Phi) data further suggest that the domain walls in the CoPt film are of the Neel type and hence do not cause any flux in the superconducting layer. A small, but distinct increase in the low-field critical current of the CoPt-NbN couple is seen when the magnetic layer has perpendicular anisotropy.Comment: 9 figure

Modeling of field singularities at dielectric edges using grid based methods

Electric field singularities at sharp metallic edges or at a dielectric contact line can be described analytically by asymptotic expressions. The a priori known form of the field distribution in the vicinity of these edges can be used to construct numerical methods with improved accuracy. This contribution focuses on a modified Finite Integration Technique and on a Discontinuous Galerkin Method with singular approximation functions. Both methods are able to handle field singularities at perfectly electric conducting as well as at dielectric edges. The numerical accuracy of these methods is investigated in a number of simulation examples including static and dynamic field problems

From Transition Systems to Variability Models and from Lifted Model Checking Back to UPPAAL

Variational systems (system families) allow effective building of many custom system variants for various configurations. Lifted (family-based) verification is capable of verifying all variants of the family simultaneously, in a single run, by exploiting the similarities between the variants. These algorithms scale much better than the simple enumerative “brute-force” way. Still, the design of family-based verification algorithms greatly depends on the existence of compact variability models (state representations). Moreover, developing the corresponding family-based tools for each particular analysis is often tedious and labor intensive.In this work, we make two contributions. First, we survey the history of development of variability models of computation that compactly represent behavior of variational systems. Second, we introduce variability abstractions that simplify variability away to achieve efficient lifted (family-based) model checking for real-time variability models. This reduces the cost of maintaining specialized family-based real-time model checkers. Real-time variability models can be model checked using the standard UPPAAL. We have implemented abstractions as syntactic source-to-source transformations on UPPAAL input files, and we illustrate the practicality of this method on a real-time case study.Both authors are supported by The Danish Council for Independent Research under a Sapere Aude project, VARIETE

Local Properties of the Potential Energy Landscape of a Model Glass: Understanding the Low Temperature Anomalies

Though the existence of two-level systems (TLS) is widely accepted to explain low temperature anomalies in the sound absorption, heat capacity, thermal conductivity and other quantities, an exact description of their microscopic nature is still lacking. We performed computer simulations for a binary Lennard-Jones system, using a newly developed algorithm to locate double-well potentials (DWP) and thus two-level systems on a systematic basis. We show that the intrinsic limitations of computer simulations like finite time and finite size problems do not hamper this analysis. We discuss how the DWP are embedded in the total potential energy landscape. It turns out that most DWP are connected to the dynamics of the smaller particles and that these DWP are rather localized. However, DWP related to the larger particles are more collective

Strain dependence of the acoustic properties of amorphous metals below 1K: Evidence for the interaction between tunneling states

We have conducted a thorough study of the acoustic properties between 10^-4 and 1 Kelvin for the amorphous metal Zr_x Cu_1-x (x=0.3 and x=0.4), by measuring the relative change of sound velocity dv/v and internal friction Q^-1 as a function of temperature and also of the applied strain, in both superconducting and normal state. We have found that when plotted versus the ratio of strain energy to thermal energy, all measurements display the same behavior: a crossover from a linear regime of ``independent'' tunneling systems at very low strains and/or high enough temperatures to a nonlinear regime where dv/v and Q^-1 depend on applied strain and the tunneling systems cannot be considered as independent.Comment: 4 pages, 4 figures (submitted to PRL

Cell adhesion and cortex contractility determine cell patterning in the Drosophila retina

Hayashi and Carthew (Nature 431 [2004], 647) have shown that the packing of cone cells in the Drosophila retina resembles soap bubble packing, and that changing E- and N-cadherin expression can change this packing, as well as cell shape. The analogy with bubbles suggests that cell packing is driven by surface minimization. We find that this assumption is insufficient to model the experimentally observed shapes and packing of the cells based on their cadherin expression. We then consider a model in which adhesion leads to a surface increase, balanced by cell cortex contraction. Using the experimentally observed distributions of E- and N-cadherin, we simulate the packing and cell shapes in the wildtype eye. Furthermore, by changing only the corresponding parameters, this model can describe the mutants with different numbers of cells, or changes in cadherin expression.Comment: revised manuscript; 8 pages, 6 figures; supplementary information not include