Quantification of propidium iodide delivery with millisecond electric pulses: A model study

A model study of propidium iodide delivery with millisecond electric pulses is presented; this work is a companion of the experimental efforts by Sadik et al. [1]. Both membrane permeabilization and delivery are examined with respect to six extra-cellular conductivities. The transmembrane potential of the permeabilized regions exhibits a consistent value, which corresponds to a bifurcation point in the pore-radius-potential relation. Both the pore area density and membrane conductance increase with an increasing extra-cellular conductivity. On the other hand, the inverse correlation between propidium iodide delivery and extra-cellular conductivity as observed in the experiments is quantitatively captured by the model. This agreement confirms that this behavior is primarily mediated by electrophoretic transport during the pulse. The results suggest that electrophoresis is important even for the delivery of small molecules such as propidium iodide. The direct comparison between model prediction and experimental data presented in this work helps validate the former as a robust predictive tool for the study of electroporation

Component selection and smoothing in multivariate nonparametric regression

We propose a new method for model selection and model fitting in multivariate nonparametric regression models, in the framework of smoothing spline ANOVA. The ``COSSO'' is a method of regularization with the penalty functional being the sum of component norms, instead of the squared norm employed in the traditional smoothing spline method. The COSSO provides a unified framework for several recent proposals for model selection in linear models and smoothing spline ANOVA models. Theoretical properties, such as the existence and the rate of convergence of the COSSO estimator, are studied. In the special case of a tensor product design with periodic functions, a detailed analysis reveals that the COSSO does model selection by applying a novel soft thresholding type operation to the function components. We give an equivalent formulation of the COSSO estimator which leads naturally to an iterative algorithm. We compare the COSSO with MARS, a popular method that builds functional ANOVA models, in simulations and real examples. The COSSO method can be extended to classification problems and we compare its performance with those of a number of machine learning algorithms on real datasets. The COSSO gives very competitive performance in these studies.Comment: Published at http://dx.doi.org/10.1214/009053606000000722 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Exploring Extended Scalar Sectors with Di-Higgs Signals: A Higgs EFT Perspective

We consider extended scalar sectors of the Standard Model as ultraviolet-complete motivations for studying the effective Higgs self-interaction operators of the Standard Model effective field theory. We investigate all motivated heavy scalar models which generate the dimension-6 effective operator, $|H|^6$, at tree level and proceed to identify the full set of tree-level dimension-six operators by integrating out the heavy scalars. Of seven models which generate $|H|^6$ at tree level only two, quadruplets of hypercharge $Y=3Y_H$ and $Y=Y_H$, generate only this operator. Next we perform global fits to constrain relevant Wilson coefficients from the LHC single Higgs measurements as well as the electroweak oblique parameters $S$ and $T$. We find that the $T$ parameter puts very strong constraints on the Wilson coefficient of the $|H|^6$ operator in the triplet and quadruplet models, while the singlet and doublet models could still have Higgs self-couplings which deviate significantly from the standard model prediction. To determine the extent to which the $|H|^6$ operator could be constrained, we study the dihiggs signatures at the future 100 TeV collider and explore future sensitivity of this operator. Projected onto the Higgs potential parameters of the extended scalar sectors, with $3$ ab$^{-1}$ luminosity data we will be able to explore the Higgs potential parameters in all seven models.Comment: 25 pages, 11 figures, 6 tables; version 3: match the JHEP published versio