KPZ equation in one dimension and line ensembles

For suitably discretized versions of the Kardar-Parisi-Zhang equation in one space dimension exact scaling functions are available, amongst them the stationary two-point function. We explain one central piece from the technology through which such results are obtained, namely the method of line ensembles with purely entropic repulsion.Comment: Proceedings STATPHYS22, Bangalore, 200

Prospects for cooling nanomechanical motion by coupling to a superconducting microwave resonator

Recent theoretical work has shown that radiation pressure effects can in principle cool a mechanical degree of freedom to its ground state. In this paper, we apply this theory to our realization of an opto-mechanical system in which the motion of mechanical oscillator modulates the resonance frequency of a superconducting microwave circuit. We present experimental data demonstrating the large mechanical quality factors possible with metallic, nanomechanical beams at 20 mK. Further measurements also show damping and cooling effects on the mechanical oscillator due to the microwave radiation field. These data motivate the prospects for employing this dynamical backaction technique to cool a mechanical mode entirely to its quantum ground state.Comment: 6 pages, 6 figure

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe

On the partial connection between random matrices and interacting particle systems

In the last decade there has been increasing interest in the fields of random matrices, interacting particle systems, stochastic growth models, and the connections between these areas. For instance, several objects appearing in the limit of large matrices arise also in the long time limit for interacting particles and growth models. Examples of these are the famous Tracy-Widom distribution functions and the Airy_2 process. The link is however sometimes fragile. For example, the connection between the eigenvalues in the Gaussian Orthogonal Ensembles (GOE) and growth on a flat substrate is restricted to one-point distribution, and the connection breaks down if we consider the joint distributions. In this paper we first discuss known relations between random matrices and the asymmetric exclusion process (and a 2+1 dimensional extension). Then, we show that the correlation functions of the eigenvalues of the matrix minors for beta=2 Dyson's Brownian motion have, when restricted to increasing times and decreasing matrix dimensions, the same correlation kernel as in the 2+1 dimensional interacting particle system under diffusion scaling limit. Finally, we analyze the analogous question for a diffusion on (complex) sample covariance matrices.Comment: 31 pages, LaTeX; Added a section concerning the Markov property on space-like path

Hipster: Integrating Theory Exploration in a Proof Assistant

This paper describes Hipster, a system integrating theory exploration with the proof assistant Isabelle/HOL. Theory exploration is a technique for automatically discovering new interesting lemmas in a given theory development. Hipster can be used in two main modes. The first is exploratory mode, used for automatically generating basic lemmas about a given set of datatypes and functions in a new theory development. The second is proof mode, used in a particular proof attempt, trying to discover the missing lemmas which would allow the current goal to be proved. Hipster's proof mode complements and boosts existing proof automation techniques that rely on automatically selecting existing lemmas, by inventing new lemmas that need induction to be proved. We show example uses of both modes

Cost-effective intervention thresholds against osteoporotic fractures based on FRAX® in Switzerland

Summary: FRAX-based cost-effective intervention thresholds in the Swiss setting were determined. Assuming a willingness to pay at 2× Gross Domestic Product per capita, an intervention aimed at reducing fracture risk in women and men with a 10-year probability for a major osteoporotic fracture at or above 15% is cost-effective. Introduction: The fracture risk assessment algorithm FRAX® has been recently calibrated for Switzerland. The aim of the present analysis was to determine FRAX-based fracture probabilities at which intervention becomes cost-effective. Methods: A previously developed and validated state transition Markov cohort model was populated with Swiss epidemiological and cost input parameters. Cost-effective FRAX-based intervention thresholds (cost-effectiveness approach) and the cost-effectiveness of intervention with alendronate (original molecule) in subjects with a FRAX-based fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk factor (translational approach) were calculated based on the Swiss FRAX model and assuming a willingness to pay of 2 times Gross Domestic Product per capita for one Quality-adjusted Life-Year. Results: In Swiss women and men aged 50years and older, drug intervention aimed at decreasing fracture risk was cost-effective with a 10-year probability for a major osteoporotic fracture at or above 13.8% (range 10.8% to 15.0%) and 15.1% (range 9.9% to 19.9%), respectively. Age-dependent variations around these mean values were modest. Using the translational approach, treatment was cost-effective or cost-saving after the age 60years in women and 55 in men who had previously sustained a fragility fracture. Using the latter approach leads to considerable underuse of the current potential for cost-effective interventions against fractures. Conclusions: Using a FRAX-based intervention threshold of 15% for both women and men should permit cost-effective access to therapy to patients at high fracture probability based on clinical risk factors and thereby contribute to further reduce the growing burden of osteoporotic fractures in Switzerlan

Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies