Multiple Correspondence Analysis via Polynomial Transformations of Ordered Categorical Variables

We present an alternative approach to Multiple Correspondence Analysis (MCA) that is appropriate when the data consist of ordered categorical variables. MCA displays objects (individuals, units) and variables as individual points and sets of category points in a low-dimensional space. We propose a hybrid decomposition on the basis of the classical indicator super-matrix, using the singular value decomposition, and the bivariate moment decomposition by orthogonal polynomials. When compared to standard MCA, the hybrid decomposition will give the same representation of the categories of the variables, but additionally, we obtain a clear association interpretation among the categories in terms of linear, quadratic and higher order components. Moreover, the graphical display of the individual units will show an automatic clustering.     

The runt test for multimodality

Single linkage clusters on a set of points are the maximal connected sets in a graph constructed by connecting all points closer than a given threshold distance. The complete set of single linkage clusters is obtained from all the graphs constructed using different threshold distances. The set of clusters forms a hierarchical tree, in which each non-singleton cluster divides into two or more subclusters; the runt size for each single linkage cluster is the number of points in its smallest subcluster. The maximum runt size over all single linkage clusters is our proposed test statistic for assessing multimodality. We give significance levels of the test for two null hypotheses, and consider its power against some bimodal alternatives. Research partially supported by NSF Grant No. DMS-8617919.     

Resistant orthogonal procrustes analysis

In this paper two alternative loss criteria for the least squares Procrustes problem are studied. These alternative criteria are based on the Huber function and on the more radical biweight function, which are designed to be resistant to outliers. Using iterative majorization it is shown how a convergent reweighted least squares algorithm can be developed. In asimulation study it turns out that the proposed methods perform well over a specific range of contamination. When a uniform dilation factor is included, mixed results are obtained. The methods also yield a set of weights that can be used for diagnostic purposes.     

A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles

Poly(MePEG₂₀₀₀cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.Received 4 March 2005; accepted 14 April 2005     

Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.Received 17 February 2005; received after revision 1 May 2005; accepted 7 Juni 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34+ cells and HSPCs expanded with primary hMSCs. Received 21 June 2005; received after revision 30 July 2005; accepted 24 August 2005     

Structural and dynamical features contributing to thermostability in α-amylases

In recent years an increasing number of studies on thermophilic and hyperthermophilic proteins aiming to elucidate determinants of protein thermostability have yielded valuable insights about the relevant mechanisms. In particular, comparison of homologous enzymes with different thermostabilities (isolated from psychrophilic, mesophilic, thermophilic and hyperthermophilic organsims) offers a unique opportunity to determine the strategies of thermal adaptation. In this respect, the medium-sized amylolytic enzyme α-amylase is a well-established representative. Various studies on α-amylases with very different thermostabilities (melting temperature T_m = 40–110°C) report structural and dynamical features as well as thermodynamical properties which are supposed to play key roles in thermal adaptation. Here, results from selected homologous α-amylases are presented and discussed with respect to some new and recently proposed strategies to achieve thermostability.Received 28 February 2005; received after revision 29 April 2005; accepted 19 May 2005