A Monte Carlo evaluation of three methods to detect local dependence in binary data latent class models

Binary data latent class analysis is a form of model-based clustering applied in a wide range of fields. A central assumption of this model is that of conditional independence of responses given latent class membership, often referred to as the “local independence” assumption. The results of latent class analysis may be severely biased when this crucial assumption is violated; investigating the degree to which bivariate relationships between observed variables fit this hypothesis therefore provides vital information. This article evaluates three methods of doing so. The first is the commonly applied method of referring the so-called “bivariate residuals” to a Chi-square distribution. We also introduce two alternative methods that are novel to the investigation of local dependence in latent class analysis: bootstrapping the bivariate residuals, and the asymptotic score test or “modification index”. Our Monte Carlo simulation indicates that the latter two methods perform adequately, while the first method does not perform as intended.     

Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots

Kaletra® (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeutic drug monitoring of lopinavir and ritonavir concentrations in whole blood and in plasma from HIV-1-infected children. Whole blood was blotted onto dried blood spot (DBS) collecting cards, and plasma was collected simultaneously. DBS collecting cards were extracted by an acetonitrile/water mixture while plasma samples were deproteinized with acetone. Drug concentrations were determined by matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (MALDI-QqQ-MS/MS). The application of DBS made it possible to measure lopinavir and ritonavir in whole blood in therapeutically relevant concentrations. The MALDI-QqQ-MS/MS plasma assay was successfully cross-validated with a commonly used high-performance liquid chromatography (HPLC)–ultraviolet (UV) assay for the therapeutic drug monitoring (TDM) of HIV-1-infected patients, and it showed comparable performance characteristics. Observed DBS concentrations showed as well, a good correlation between plasma concentrations obtained by MALDI-QqQ-MS/MS and those obtained by the HPLC-UV assay. Application of DBS for TDM proved to be a good alternative to the normally used plasma screening. Moreover, collection of DBS requires small amounts of whole blood which can be easily performed especially in (very) young children where collection of large whole blood amounts is often not possible. DBS is perfectly suited for TDM of HIV-1-infected children; but nevertheless, DBS can also easily be applied for TDM of patients in areas with limited or no laboratory facilities.     

Impact of steric interactions on the helical transition in assemblies of discotic molecules

We investigate theoretically the effect of excluded-volume interactions on the helical configurational transition of supramolecular assemblies in solutions of chiral disklike molecules. To this end, we set up a second-virial theory within the context of the helical self-assembly of rodlike objects. We find that interaggregate interactions shift both the helical-transition point and the sharpness of the transition. For realistic values of the model parameters, the helical-transition temperature shifts by several degrees, and the more so the higher the concentration of assembling material. The mean aggregation number is also affected by the interactions, albeit only by a modest amount, unless the solution becomes very concentrated.     

Amplification of chirality in benzene tricarboxamide helical supramolecular polymers

The chirality of benzene tricarboxamides is expressed and amplified into the helicity of self-assembled columnar aggregates according to 'sergeants and soldiers' and 'majority rules' principles; the strength of the amplification is analysed quantitatively and the effect of the number of chiral groups in the sergeants is studied.     

Diastereopure Fe(II) and Zn(II) complexes derived from a tridentate N,N',N-bis(methyl-L-prolinate)-substituted pyridine ligand

A series of mononuclear iron(II) and zinc(II) complexes of the new chiral Py(ProMe)2 ligand (Py(ProMe)2 = 2,6-bis[[(S)-2-(methyloxycarbonyl)-1-pyrrolidinyl]methyl]pyridine) have been prepared. The molecular geometry in the solid state (X-ray crystal structures) of the complexes [FeCl2(Py(ProMe)2)] (1), [ZnCl2(Py(ProMe)2)] (2), [Fe(OTf)2(Py(ProMe)2)] (3), [Fe(Py(ProMe)2)(OH2)2](OTf)2 (4), and [Zn(OTf)(Py(ProMe)2)](OTf) (5) are reported. They all show a meridional NN'N coordination of the Py(ProMe)2 ligand. The bis-chloride derivatives 1 and 2 represent neutral isostructural five-coordinated complexes with a distorted geometry around the metal center. Unusual seven-coordinate iron(II) complexes 3 and 4 having a pentagonal bipyramidal geometry were obtained using weakly coordinating triflate anions. The reaction of Zn(OTf)2 with the Py(ProMe)2 ligand afforded complex 5 with a distorted octahedral geometry around the zinc center. All complexes were formed as single diastereoisomers. In the case of complexes 3-5, the oxygen atoms of both carbonyl groups of the ligand are also coordinated to the metal. The stereochemistry of the coordinated tertiary amine donors in complexes 3-5 is of opposite configuration as in complexes 1 and 2 as a result of the planar penta-coordination of the ligand Py(ProMe)2. Complexes 1, 2, and 5 have an overall -configuration at their metal center, while the Fe(II) ion in complexes 3 and 4 has the opposite delta-configuration (crystal structures and CD measurements). The magnetic moments of iron complexes 1, 3, and 4 correspond to that of high-spin d6 Fe(II) complexes. The solution structures of complexes 1-5 were characterized by means of UV-vis, IR, conductivity, and CD measurements and their electrochemical behavior. These studies showed that the coordination environment of 1 and 2 observed in the solid state is maintained in solution. In coordinating solvents, the triflate anion (3, 5) or water (4) co-ligands of complexes 3-5 are replaced by solvent molecules with retention of the original pentagonal bipyramidal and octahedral geometry, respectively.     

Substructure mining using elaborate chemical representation

Substructure mining algorithms are important drug discovery tools since they can find substructures that affect physicochemical and biological properties. Current methods, however, only consider a part of all chemical information that is present within a data set of compounds. Therefore, the overall aim of our study was to enable more exhaustive data mining by designing methods that detect all substructures of any size, shape, and level of chemical detail. A means of chemical representation was developed that uses atomic hierarchies, thus enabling substructure mining to consider general and/or highly specific features. As a proof-of-concept, the efficient, multipurpose graph mining system Gaston learned substructures of any size and shape from a mutagenicity data set that was represented in this manner. From these substructures, we extracted a set of only six nonredundant, discriminative substructures that represent relevant biochemical knowledge. Our results demonstrate the individual and synergistic importance of elaborate chemical representation and mining for nonlinear substructures. We conclude that the combination of elaborate chemical representation and Gaston provides an excellent method for 2D substructure mining as this recipe systematically explores all substructures in different levels of chemical detail.     

Analysis of in situ EXAFS data of supported metal catalysts using the third and fourth cumulant

X-Ray absorption spectra of supported Pt catalysts with various Pt cluster sizes were collected between 77 and 673 K, in inert and hydrogen atmospheres. When analyzing these spectra with the standard EXAFS equation, a Pt-Pt bond contraction and a large increase in the inner potential correction were observed with increasing temperature. These errors are up to 0.08 A and 10 eV for clusters of 1 nm diameter. They were corrected by including the third and fourth cumulants as fit parameters. Fit guidelines were developed to analyze EXAFS data of supported metal catalysts collected at elevated temperatures, allowing for asymmetry and broadening or sharpening of the pair distribution function. These comprise fixing fit parameters, using different k-weightings and identifying trends in a series of experiments. By fitting the EXAFS spectra using these guidelines, it was determined that in small Pt clusters the Pt-Pt bond is 0.10 A shorter than in bulk Pt. These contracted bonds relax to distances near that of bulk Pt upon hydrogen chemisorption.     

Photocatalyzed Hydrogen Evolution from Water by a Composite Catalyst of NH2‐MIL‐125(Ti) and Surface Nickel(II) Species

A composite of the metal–organic framework (MOF) NH₂‐MIL‐125(Ti) and molecular and ionic nickel(II) species, catalyzed hydrogen evolution from water under UV light. In 95 v/v % aqueous conditions the composite produced hydrogen in quantities two orders of magnitude higher than that of the virgin framework and an order of magnitude greater than that of the molecular catalyst. In a 2 v/v % water and acetonitrile mixture, the composite demonstrated a TOF of 28 mol H₂ g(Ni)^?1 h^?1 and remained active for up to 50 h, sustaining catalysis for three times longer and yielding 20‐fold the amount of hydrogen. Appraisal of physical mixtures of the MOF and each of the nickel species under identical photocatalytic conditions suggest that similar surface localized light sensitization and proton reduction processes operate in the composite catalyst. Both nickel species contribute to catalytic conversion, although different activation behaviors are observed.     

Equivariant Hopf bifurcation for neutral functional differential equations

In this paper we employ an equivariant Lyapunov-Schmidt procedure to give a clearer understanding of the one-to-one correspondence of the periodic solutions of a system of neutral functional differential equations with the zeros of the reduced bifurcation map, and then set up equivariant Hopf bifurcation theory. In the process we derive criteria for the existence and direction of branches of bifurcating periodic solutions in terms of the original system, avoiding the process of center manifold reduction.