Identification of metabolites of halofantrine, a new candidate anti-malarial drug, by gas chromatography-mass spectrometry.

Two previously unknown metabolites of halofantrine, a candidate anti-malarial drug, have been isolated by thin-layer chromatography from the plasma of dogs administered a single oral dose of 60 mg/kg. Their identifies were investigated after trimethylsilylation by gas chromatography-mass spectrometry under electron-impact and negative-ion chemical ionization conditions. The structural assignment was further confirmed by using a combination of elemental composition analysis of all the isotope peaks at low mass resolution and isotope pattern matching. These two metabolites were formed by modification of the dibutylaminopropyl side-chain of the parent compound involving deamination and oxidation or reduction.     

The Spirit Is Willing: Nonlinearity, Bifurcations, and Mental Control

In recent years there has been considerable interest in the construction of nonlinear models of the dynamics of human behavior. In this exploratory article we argue that attempts at controlling problematic thoughts, emotions, or behaviors can lead to nonlinearity in mental/behavioral dynamics. We illustrate our model by fitting threshold autoregression models to self-recorded time series of the daily highs in intensity of anxiety and obsessive ruminations, kept by an individual in therapy for this problem. In our discussion, we raise the possibility that bifurcations that occur in this nonlinear model may offer insight into mental control paradoxes.     

A minimum average risk approach to shrinkage estimators of the normal mean

For the problem of estimating the normal mean based on a random sample X ₁,...,X _n when a prior value ₀ is available, a class of shrinkage estimators % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-qqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xHapdbiqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaubeaeqaje% aWbaGaamOBaaWcbeqdbaGafqiVd0MbaKaaaaGccaqGGaGaaiikaiaa% dUgacaGGPaGaeyypa0Jaam4AaiaacIcadaqfqaqabKqaahaacaqGUb% aaleqaneaacaqGubaaaOGaaiykaiaabccadaqfqaqabKqaahaacaWG% UbaaleqaneaaceqGybGbaebaaaGccaqGGaGaey4kaSIaaeiiaiaacI% cacaaIXaGaaeiiaiabgkHiTiaabccacaWGRbGaaiikamaavababeqc% baCaaiaab6gaaSqab0qaaiaabsfaaaGccaGGPaGaaiykamaavababe% qcbaCaaiaad6gaaSqab0qaaiabeY7aTbaaaaa!5615!\[\mathop {\hat \mu }\nolimits_n {\rm{ }}(k) = k(\mathop {\rm{T}}\nolimits_{\rm{n}} ){\rm{ }}\mathop {{\rm{\bar X}}}\nolimits_n {\rm{ }} + {\rm{ }}(1{\rm{ }} - {\rm{ }}k(\mathop {\rm{T}}\nolimits_{\rm{n}} ))\mathop \mu \nolimits_n \] is considered, where % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-qqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xHapdbiqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaubeaeqaje% aWbaGaamOBaaWcbeqcdawaaiaadsfaaaGccaqGGaGaaeypaiaabcca% caWGUbWaaWbaaSqabeaacaaIXaGaai4laiaaikdaaaGccaGGOaWaa0% aaaeaacaWGybaaamaaBaaajeaWbaGaamOBaaWcbeaakiaabccacqGH% sislcaqGGaWaaubeaeqajeaWbaGaaGimaaWcbeqdbaGaaeiVdaaaki% aacMcacaqGGaGaae4laiabeccaGiabeo8aZbaa!4C33!\[\mathop T\nolimits_n {\rm{ = }}n^{1/2} (\overline X _n {\rm{ }} - {\rm{ }}\mathop {\rm{\mu }}\nolimits_0 ){\rm{ /}} \sigma \] and k is a weight function. For certain choices of k, % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-qqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xHapdbiqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaubeaeqaje% aWbaGaamOBaaWcbeqdbaGafqiVd0MbaKaaaaGccaqGGaGaaiikaiaa% dUgacaGGPaaaaa!3CEE!\[\mathop {\hat \mu }\nolimits_n {\rm{ }}(k)\] coincides with previously studied preliminary test and shrinkage estimators. We consider choosing k from a natural non-parametric family of weight functions so as to minimize average risk relative to a specified prior p. We study how, by varying p, the MSE efficiency (relative to \-X) properties of % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-qqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xHapdbiqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaubeaeqaje% aWbaGaamOBaaWcbeqdbaGafqiVd0MbaKaaaaGccaqGGaGaaiikaiaa% dUgacaGGPaaaaa!3CEE!\[\mathop {\hat \mu }\nolimits_n {\rm{ }}(k)\] can be controlled. In the process, a certain robustness property of the usual family of posterior mean estimators, corresponding to the conjugate normal priors, is observed.     

Abelian cocycles for nonsingular ergodic transformations and the genericity of type III1 transformations

The authors prove that in the space of nonsingular transformations of a Lebesgue probability space the type III₁ ergodic transformations form a denseG set with respect to the coarse topology. They also prove that for any locally compact second countable abelian groupH, and any ergodic type III transformationT, it is generic in the space ofH-valued cocycles for the integer action given byT that the skew product ofT with the cocycle is orbit equivalent toT. Similar results are given for ergodic measure-preserving transformations as well.Research supported in part by: Nat. Sci. and Eng. Res. Council #A7163 and # U0080 F.C.A.C. Quebec, NSF Grants # MCS-8102399 and # DMS-8418431.