Optimal designs for estimating the coefficients of the lower frequencies in trigonometric regression models

In the common Fourier regression model we determine the optimal designs for estimating the coefficients corresponding to the lower frequencies. An analytical solution is provided which is found by an alternative characterization of c-optimal designs. Several examples are provided and the performance of the D-optimal design with respect to the estimation of the lower order coefficients is investigated. The results give a complete answer to an open question which was recently raised by Dette and Melas (2003). --trigonometric regression model,c-optimal design,Chebyshev approximation,two dimensional shape analysis

Two dimensional Berezin-Li-Yau inequalities with a correction term

We improve the Berezin-Li-Yau inequality in dimension two by adding a positive correction term to its right-hand side. It is also shown that the asymptotical behaviour of the correction term is almost optimal. This improves a previous result by Melas.Comment: 6 figure

An Integrated Decision-Support Information System on the Impact of Extreme Natural Hazards on Critical Infrastructure

In this paper, we introduce an Integrated Decision-Support Tool (IDST v2.0) which was developed as part of the INFRARISK project (https://www.infrarisk-fp7.eu/). The IDST is an online tool which demonstrates the implementation of a risk-based stress testing methodology for analyzing the potential impact of natural hazards on transport infrastructure networks. The IDST is enabled with a set of software workflow processes that allow the definition of multiple cascading natural hazards, geospatial coverage and impact on important large infrastructure, including those which are critical to transport networks in Europe. Stress tests on these infrastructure are consequently performed together with the automated generation of useful case study reports for practitioners. An exemplar stress test study using the IDST is provided in this paper. In this study, risks and consequences of an earthquake-triggered landslide scenario in Northern Italy is described. Further, it provides a step-by-step account of the developed stress testing overarching methodology which is applied to the impact on a road network of the region of interest

Decadal regional air quality simulations over Europe in present climate: near surface ozone sensitivity to external meteorological forcing

Abstract. Regional climate-air quality decadal simulations over Europe were carried out with the RegCM3/CAMx modeling system for the time slice 1991–2000, in order to study the impact of different meteorological forcing on surface ozone. The RegCM3 regional climate model was firstly constrained by the ERA40 reanalysis dataset which is considered as an experiment with perfect meteorological boundary conditions and then it was constrained by the global circulation model ECHAM5. A number of meteorological parameters were examined including the 500 mb geopotential height, solar radiation, temperature, cloud liquid water path, planetary boundary layer height and surface wind. The different RegCM meteorological forcing resulted in changes of near surface ozone over Europe ranging between ± 4 ppb for winter and summer. The area showing the greatest sensitivity in O3 during winter is central and southern Europe while in summer central north continental Europe. The different meteorological forcing impacts on the atmospheric circulation, which in turn affects cloudiness and solar radiation, temperature, wind patterns and the meteorology depended biogenic emissions. For comparison reasons, the impact of chemical boundary conditions on surface ozone was additionally examined with a series of sensitivity studies, indicating that surface ozone changes are comparable to those caused by the different meteorological forcing. These findings suggest that, when it comes to regional climate-air quality simulations, the selection of external meteorological forcing can be as important as the selection of adequate chemical lateral boundary conditions

Translational Systems Pharmacology-Based Predictive Assessment of Drug-Induced Cardiomyopathy

Drug-induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug’s signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs’ signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0.1%. The ILP-augmented modeling increased prediction accuracy from 79% to 88% (sensitivity: 88%; specificity: 89%) under leave-one-out cross validation. The ILP-constructed signaling networks of drugs were better predictors than DEGs. Per literature, the microRNAs that reportedly regulate expression of our six top predictors are of diagnostic value for natural heart failure or doxorubicin-induced cardiomyopathy. This translational predictive modeling might uncover potential biomarkers

Identification of drug-specific pathways based on gene expression data: application to drug induced lung injury

Identification of signaling pathways that are functional in a specific biological context is a major challenge in systems biology, and could be instrumental to the study of complex diseases and various aspects of drug discovery. Recent approaches have attempted to combine gene expression data with prior knowledge of protein connectivity in the form of a PPI network, and employ computational methods to identify subsets of the protein–protein-interaction (PPI) network that are functional, based on the data at hand. However, the use of undirected networks limits the mechanistic insight that can be drawn, since it does not allow for following mechanistically signal transduction from one node to the next. To address this important issue, we used a directed, signaling network as a scaffold to represent protein connectivity, and implemented an Integer Linear Programming (ILP) formulation to model the rules of signal transduction from one node to the next in the network. We then optimized the structure of the network to best fit the gene expression data at hand. We illustrated the utility of ILP modeling with a case study of drug induced lung injury. We identified the modes of action of 200 lung toxic drugs based on their gene expression profiles and, subsequently, merged the drug specific pathways to construct a signaling network that captured the mechanisms underlying Drug Induced Lung Disease (DILD). We further demonstrated the predictive power and biological relevance of the DILD network by applying it to identify drugs with relevant pharmacological mechanisms for treating lung injury.Institute for Collaborative Biotechnologies (Grant W911NF-09-0001

Towards Canonical Quantum Gravity for G1 Geometries in 2+1 Dimensions with a Lambda--Term

The canonical analysis and subsequent quantization of the (2+1)-dimensional action of pure gravity plus a cosmological constant term is considered, under the assumption of the existence of one spacelike Killing vector field. The proper imposition of the quantum analogues of the two linear (momentum) constraints reduces an initial collection of state vectors, consisting of all smooth functionals of the components (and/or their derivatives) of the spatial metric, to particular scalar smooth functionals. The demand that the midi-superspace metric (inferred from the kinetic part of the quadratic (Hamiltonian) constraint) must define on the space of these states an induced metric whose components are given in terms of the same states, which is made possible through an appropriate re-normalization assumption, severely reduces the possible state vectors to three unique (up to general coordinate transformations) smooth scalar functionals. The quantum analogue of the Hamiltonian constraint produces a Wheeler-DeWitt equation based on this reduced manifold of states, which is completely integrated.Comment: Latex 2e source file, 25 pages, no figures, final version (accepted in CQG

Effects on surface atmospheric photo-oxidants over Greece during the total solar eclipse event of 29 March 2006

International audienceThis study investigates the effects of the total solar eclipse of 29 March 2006 on surface air-quality levels over Greece based on observations at a number of sites in conjunction with chemical box modelling and 3-D air-quality modelling. Emphasis is given on surface ozone and other photooxidants at four Greek sites Kastelorizo, Finokalia (Crete), Pallini (Athens) and Thessaloniki, which are located at gradually increasing distances from the path of the eclipse totality and are characterized by different air pollution levels. The eclipse offered the opportunity to test our understanding of air pollution build-up and the response of the gas-phase chemistry of photo-oxidants during a photolytical perturbation using both a photochemical box model and a regional air-quality offline model based on the modeling system WRF/CAMx. At the relatively unpolluted sites of Kastelorizo and Finokalia no clear impact of the solar eclipse on surface O3, NO2 and NO concentrations can be deduced from the observations and model simulations as the calculated changes in net ozone production rates between eclipse and non eclipse conditions are rather small compared to the ozone variability and hence the solar eclipse effects on ozone can be easily masked by transport. At the polluted sites of Thessaloniki and Pallini, the solar eclipse effects on O3, NO2 and NO concentrations are clearly revealed from both the measurements and 3-D air-quality modeling with the net effect being a decrease in O3 and NO and an increase in NO2 as NO2 formed from the reaction of O3 with NO while at the same time NO2 is not efficiently photolysed. It is evident from the 3-D air quality modeling over Greece that the maximum effects of the eclipse on O3, NO2 and NO are reflected at the large urban agglomerations of Athens, and Thessaloniki where the maximum of the emissions occur

Towards Canonical Quantum Gravity for Geometries Admitting Maximally Symmetric Two-dimensional Surfaces

The 3+1 (canonical) decomposition of all geometries admitting two-dimensional space-like surfaces is exhibited. A proposal consisting of a specific re-normalization {\bf Assumption} and an accompanying {\bf Requirement} is put forward, which enables the canonical quantization of these geometries. The resulting Wheeler-deWitt equation is based on a re-normalized manifold parameterized by three smooth scalar functionals. The entire space of solutions to this equation is analytically given, exploiting the freedom left by the imposition of the {\bf Requirement} and contained in the third functional.Comment: 27 pages, no figures, LaTex2e source fil