On the Behaviour of Fligner-Wolfe-Trend Test “Control versus k Treatments” with Application in Toxicology

The behaviour of Fligner-Wolfe-trend test “control versus k treatments” was characterized by simulation. Sample size estimation took place via non-central t-distribution. Some results on asymptotic efficiency were shown and compared with simulation results for small sample sizes. A test version for umbrella alternatives was given and characterized by simulation.     

Order Parameter Dynamics of Body-scaled Hysteresis and Mode Transitions in Grasping Behavior

Several experimental studies have shown that human grasping behavior exhibits a transition from one-handed to two-handed grasping when to-be-grasped objects become larger and larger. The transition point depends on the relative size of objects measured in terms of human body-scales. Most strikingly, the transitions between the two different behavioral ‘modes’ of grasping exhibit hysteresis. That is, one-to-two hand transitions and two-to-one hand transitions occur at different relative object sizes when objects are scaled up or down in size. In our study we approach body-scaled hysteresis and mode transitions in grasping by exploiting the notion that human behavior in general results from self-organization and satisfies appropriately-defined order parameter equations. To this end, grasping transitions and grasping hysteresis are discussed from a theoretical perspective in analogy to cognitive processes defined by Haken’s neural network model for pattern recognition. In doing so, issues such as the exclusivity of grasping modes, biomechanical constraints, mode-mode interactions, single subject behavior and population behavior are explored.     

Analysis of Crossover Designs with a Categorical Response

In the analysis of two-period crossover designs, one frequently must consider the case of a categorical response with binary as a special case. These circumstances are considered in this paper and the proposed method—an extension of GART'S tests for the binary case—is similar to that of PIKE, CASAGRANDE and SMITH for the analysis of pair-matched case-control studies. The results are illustrated with a numerical example.     

Comparative genome sequence analysis of Sulfolobus acidocaldarius and 9 other isolates of its genus for factors influencing codon and amino acid usage

In the present study, major constraints for codon and amino acid usage of Sulfolobus acidocaldarius, Sulfolobus solfataricus, Sulfolobus tokodali, Sulfolobus islandis and 6 other isolates from islandicus species of genus Sulfolobus were investigated. Correspondence analysis revealed high significant correlation between the major trend of synonymous codon usage and gene expression level, as assessed by the “Codon Adaptation Index” (CAI). There is a significant negative correlation between Nc (Effective number of codons) and CAI demonstrating role of codon bias as an important determinant of codon usage. The significant correlation between major trend of synonymous codon usage and GC3s (G + C at third synonymous position) indicated dominant role of mutational bias in codon usage pattern. The result was further supported from SCUO (synonymous codon usage order) analysis. The amino acid usage was found to be significantly influenced by aromaticity and hydrophobicity of proteins. However, translational selection which causes a preference for codons that are most rapidly translated by current tRNA with multiple copy numbers was not found to be highly dominating for all studied isolates. Notably, 26 codons that were found to be optimally used by genes of S. acidocaldarius at higher expression level and its comparative analysis with 9 other isolates may provide some useful clues for further in vivo genetic studies on this genus.     

Multiple imputation methods for multivariate one-sided tests with missing data

Multivariate one-sided hypotheses testing problems arise frequently in practice. Various tests have been developed. In practice, there are often missing values in multivariate data. In this case, standard testing procedures based on complete data may not be applicable or may perform poorly if the missing data are discarded. In this article, we propose several multiple imputation methods for multivariate one-sided testing problem with missing data. Some theoretical results are presented. The proposed methods are evaluated using simulations. A real data example is presented to illustrate the methods.     

Protein folding and the order/disorder paradox

Most proteins encoded by the nuclear genome are synthesized in the cytoplasm and fold into precise 3D structures. During synthesis, the nascent polypeptide begins to fold as it traverses the large subunit of the ribosome and is assisted by molecular chaperones in attaining its precise folded/highly ordered state efficiently and in a biologically relevant timescale. Proteins that are misfolded are culled, re-routed, and marked by mechanisms such as ubiquitinylation for degradation ensuring strict quality control (QC). In addition to the highly ordered "globular" proteins, emerging evidence indicates that a large fraction of the proteome also comprises the so-called "Intrinsically Disordered Proteins" (IDPs). IDPs are proteins that lack rigid 3D structures and instead, exist as dynamic ensembles. The dynamic structures in the IDPs have many similarities with "normal" globular proteins such as the native (ordered), and non-native (molten globule, pre-molten globule, and coil-like) states seen during folding of "normal" globular proteins. However, unlike the case of the nascent globular proteins, IDPs evade being detected as "misfolded" and degraded by the cell's QC system. We refer to this paradox as the order/disorder paradox and postulate that the IDPs capitalize on their intrinsic promiscuity and ability to undergo disorder-to-order transitions upon binding to biological targets (coupled folding and binding) to escape the cell's surveillance machinery. Understanding the mechanism by which the IDPs evade the quality check has wide implications from protein folding to disease biology since the aggregation of misfolded proteins underlies several debilitating illnesses such as many neurodegenerative diseases and cancer.     

Experimental observation of increased fluctuations in an order parameter before epochs of extended brain synchronization

The identification of epileptic seizure precursors has potential clinical relevance. It is conjectured that seizures may be represented by dynamical bifurcations and that an adequate order parameter to characterize brain dynamics is the phase difference in the oscillatory activity of neural systems. In this study, the critical point hypothesis that seizures, or more generally periods of widespread high synchronization, represent bifurcations is empirically tested by monitoring the growth of fluctuations in the putative order parameter of phase differences between magnetoencephalographic and electroencephalographic signals in nearby brain regions in patients with epilepsy and normal subjects during hyperventilation. Implications of the results with regard to epileptic phenomena are discussed.     

NMR investigations of interactions between anesthetics and lipid bilayers

Interactions between anesthetics (lidocaine and short chain alcohols) and lipid membranes formed by dimyristoylphosphatidylcholine (DMPC) were studied using NMR spectroscopy. The orientational order of lidocaine was investigated using deuterium NMR on a selectively labelled compound whereas segmental ordering in the lipids was probed by two-dimensional ¹H-¹³C separated local field experiments under magic-angle spinning conditions. In addition, trajectories generated in molecular dynamics (MD) computer simulations were used for interpretation of the experimental results. Separate simulations were carried out with charged and uncharged lidocaine molecules. Reasonable agreement between experimental dipolar interactions and the calculated counterparts was observed. Our results clearly show that charged lidocaine affects significantly the lipid headgroup. In particular the ordering of the lipids is increased accompanied by drastic changes in the orientation of the P-N vector in the choline group.