Data Adaptive Ridging in Local Polynomial Regression

Abstract

When estimating a regression function or its derivatives, local polynomials are an attractive choice due to their flexibility and asymptotic performance. Seifert and Gasser proposed ridging of local polynomials to overcome problems with variance for random design while retaining their advantages. In this article we present a data-independent rule of thumb and a data-adaptive spatial choice of the ridge parameter in local linear regression. In a framework of penalized local least squares regression, the methods are generalized to higher order polynomials, to estimation of derivatives, and to multivariate designs. The main message is that ridging is a powerful tool for improving the performance of local polynomials. A rule of thumb offers drastic improvements; data-adaptive ridging brings further but modest gains in mean square error.     

Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to Promising Antiparasitic Drug Candidates

The discovery of novel drugs against animal parasites is in high demand due to drug‐resistance problems encountered around the world. Herein, the synthesis and characterization of 27 organic and organometallic derivatives of the recently launched nematocidal drug monepantel (Zolvix^®) are described. The compounds were isolated as racemates and were characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was verified by microanalysis. The molecular structures of nine compounds were confirmed by X‐ray crystallography. The anthelmintic activity of the newly designed analogues was evaluated in vitro against the economically important parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate nematocidal activity was observed for nine of the 27 compounds. Three compounds were confirmed as potentiators of a known monepantel target, the ACR‐23 ion channel. Production of reactive oxygen species may confer secondary activity to the organometallic analogues. Two compounds, namely, an organic precursor ( 3 a ) and a cymantrene analogue ( 9 a ), showed activities against microfilariae of Dirofilaria immitis in the low microgram per milliliter range.     

A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Pt^II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt^IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru^II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt^IV–Ru^II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt^IV centre is reduced to Pt^II and the axial ligands including the Ru^II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi‐target and multi‐action effect with (photo‐)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.     

Spin waves of a layered ferromagnetic electron gas

Using a first-order Green's function technique, the spin wave spectrum of a layered ferromagnetic electron system is determined in the long-wave length limit. It is shown that the spin wave stiffness is a highly anisotropic quantity. A discussion of the Stoner-Overhauser-Wohlfarth condition shows that both electron tunneling processes and a more sophisticated expression of the Coulomb interaction matrix element than the usual Hubbard form are important for the existence of ferromagnetic ordering.     

Reliability-Based Optimization of structural systems

A method to carry out a Reliability-Based Optimization (RBO) of especially nonlinear structural systems is introduced. Statistical uncertainties involving both structural and loading properties are considered. The concept is based on the separation of structural reliability analyses and the optimization procedures. Two approaches are discussed, depending on the interaction of reliability analysis and mathematical programming and the way of representation of the limit state functions (LSF) of the structure. As, for cases of practical significance, the LSF is known only pointwise it is approximated by Response Surfaces (RS). For the response calculations Finite Element (FE) procedures are utilized. Failure probabilities are determined by applying variance reducing Monte Carlo simulation (MCS) techniques such as Importance Sampling (IS). Following the reliability analysis, the optimization procedure is controlled by the NLPQL algorithm. A numerical example in terms of a template ocean platform exemplifies the procedures.Formerly Institute of Engineering Mechanics, Leopold-Franzens-University, Innsbruck, Austria     

The reaction of nitrous oxide with rhodium

A clean rhodium filament at room temperature is highly reactive towards nitrous oxide. The oxygen atom of the N₂O molecule is adsorbed with a sticking probability of 0.45 whilst the nitrogen atoms appear in the gas phase as molecular nitrogen. The room temperature uptake of oxygen is about 5 × 10¹⁴ atom cm^?2 and is independent of nitrous oxide pressure in the range 3.5 × 10^?8 to 1.1 × 10^?6 torr. The adsorption curve is of typical form with an initial region of essentially constant sticking probability. For the first 80% of adsorption at room temperature the shape is satisfactorily accounted for if molecules are able to visit 4–5 adsorption sites whilst held in a weakly-bonded precursor state.     

Photodissociation dynamics of the 2-methylallyl radical

Time- and frequency-resolved photoionization of the hydrogen atom product from a jet-cooled electronically excited 2-methylallyl radical, C4H7, provides information on the dissociation dynamics. The measured dissociation rates and kinetic energy release of 2-methylallyl and its isotopologue CD3C3H4 combined with high level ab initio calculations suggests unimolecular dissociation with methylenecyclopropane and hydrogen as the major C-H bond fission channel with no evidence for nonstatistical behavior in dissociation. Other possible dissociation and isomerization pathways are discussed based on the results of the coupled-cluster ab initio calculations.     

Towards Platinum(II) Complexes for in cellulo Applications: Synthesis,Characterization, Biological and Catalytic Evaluation

With the aim of achieving bioorthogonal intracellular catalysis, a library of platinum(II) complexes was synthesized. Their non-toxicity to living cells was demonstrated and their catalytic activity was evaluated on a cyclization reaction leading to a highly fluorescent coumarin. None of the platinum complexes showed any catalytic activity for coumarin synthesis. Still, we demonstrated that the silver salt AgSbF₆ commonly used to ‘activate’ metal catalysts by removing a chloride is a very efficient catalyst for the studied intramolecular cyclization reaction.