Penalized Regression with Correlation Based Penalty

A new regularization method for regression models is proposed. The criterion to be minimized contains a penalty term which explicitly links strength of penalization to the correlation between predictors. As the elastic net, the method encourages a grouping effect where strongly correlated predictors tend to be in or out of the model together. A boosted version of the penalized estimator, which is based on a new boosting method, allows to select variables. Real world data and simulations show that the method compares well to competing regularization techniques. In settings where the number of predictors is smaller than the number of observations it frequently performs better than competitors, in high dimensional settings prediction measures favor the elastic net while accuracy of estimation and stability of variable selection favors the newly proposed method

Boosting Correlation Based Penalization in Generalized Linear Models

In high dimensional regression problems penalization techniques are a useful tool for estimation and variable selection. We propose a novel penalization technique that aims at the grouping effect which encourages strongly correlated predictors to be in or out of the model together. The proposed penalty uses the correlation between predictors explicitly. We consider a simple version that does not select variables and a boosted version which is able to reduce the number of variables in the model. Both methods are derived within the framework of generalized linear models. The performance is evaluated by simulations and by use of real world data sets

Combining Quadratic Penalization and Variable Selection via Forward Boosting

Quadratic penalties can be used to incorporate external knowledge about the association structure among regressors. Unfortunately, they do not enforce single estimated regression coefficients to equal zero. In this paper we propose a new approach to combine quadratic penalization and variable selection within the framework of generalized linear models. The new method is called Forward Boosting and is related to componentwise boosting techniques. We demonstrate in simulation studies and a real-world data example that the new approach competes well with existing alternatives especially when the focus is on interpretable structuring of predictors

A unique serpin P1′ glutamate and a conserved β-sheet C arginine are key residues for activity, protease recognition and stability of serpinA12 (vaspin)

SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has multiple beneficial effects on metabolic, inflammatory and atherogenic processes related to obesity. KLK7 (kallikrein 7) is the only known protease target of vaspin to date and is inhibited with a moderate inhibition rate. In the crystal structure, the cleavage site (P1-P1′) of the vaspin reactive centre loop is fairly rigid compared with the flexible residues before P2, possibly supported by an ionic interaction of P1′ glutamate (Glu379) with an arginine residue (Arg302) of the β-sheet C. A P1′ glutamate seems highly unusual and unfavourable for the protease KLK7. We characterized vaspin mutants to investigate the roles of these two residues in protease inhibition and recognition by vaspin. Reactive centre loop mutations changing the P1′ residue or altering the reactive centre loop conformation significantly increased inhibition parameters, whereas removal of the positive charge within β-sheet C impeded the serpin–protease interaction. Arg302 is a crucial contact to enable vaspin recognition by KLK7 and it supports moderate inhibition of the serpin despite the presence of the detrimental P1′ Glu379, which clearly represents a major limiting factor for vaspin-inhibitory activity. We also show that the vaspin-inhibition rate for KLK7 can be modestly increased by heparin and demonstrate that vaspin is a heparin-binding serpin. Noteworthily, we observed vaspin as a remarkably thermostable serpin and found that Glu379 and Arg302 influence heat-induced polymerization. These structural and functional results reveal the mechanistic basis of how reactive centre loop sequence and exosite interaction in vaspin enable KLK7 recognition and regulate protease inhibition as well as stability of this adipose tissue-derived serpin

Crystal structure of cleaved vaspin (serpinA12)

The adipokine vaspin (serpinA12) is mainly expressed in white adipose tissue and exhibits various beneficial effects on obesity-related processes. Kallikrein 7 is the only known target protease of vaspin and is inhibited by the classical serpin inhibitory mechanism involving a cleavage of the reactive center loop between P1 (M378) and P1′ (E379). Here, we present the X-ray structure of vaspin, cleaved between M378 and E379. We provide a comprehensive analysis of differences between the uncleaved and cleaved forms in the shutter, breach, and hinge regions with relation to common molecular features underlying the serpin inhibitory mode. Furthermore, we point out differences towards other serpins and provide novel data underlining the remarkable stability of vaspin. We speculate that the previously reported FKGx1Wx2x3 motif in the breach region may play a decisive role in determining the reactive center loop configuration in the native vaspin state and might contribute to the high thermostability of vaspin. Thus, this structure may provide a basis for future mutational studies

Collision Dynamics and Solvation of Water Molecules in a Liquid Methanol Film

Environmental molecular beam experiments are used to examine water interactions with liquid methanol films at temperatures from 170 K to 190 K. We find that water molecules with 0.32 eV incident kinetic energy are efficiently trapped by the liquid methanol. The scattering process is characterized by an efficient loss of energy to surface modes with a minor component of the incident beam that is inelastically scattered. Thermal desorption of water molecules has a well characterized Arrhenius form with an activation energy of 0.47{\pm}0.11 eV and pre-exponential factor of 4.6 {\times} 10^(15{\pm}3) s^(-1). We also observe a temperature dependent incorporation of incident water into the methanol layer. The implication for fundamental studies and environmental applications is that even an alcohol as simple as methanol can exhibit complex and temperature dependent surfactant behavior.Comment: 8 pages, 5 figure

Dynamic Oligopoly Pricing: Evidence from the Airline Industry

We explore how pricing dynamics in the European airline industry vary with the competitive environment. Our results highlight substantial variations in pricing dynamics that are consistent with a theory of intertemporal price discrimination. First, the rate at which prices increase towards the scheduled travel date is decreasing in competition, supporting the idea that competition restrains the ability of airlines to price-discriminate. Second, the sensitivity to competition is substantially increasing in the heterogeneity of the customer base, reflecting further that restraints on price discrimination are only relevant if there is initial scope for price discrimination. These patterns are quantitatively important, explaining about 83 percent of the total within-flight price dispersion, and explaining 17 percent of the observed cross-market variation of pricing dynamics