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A circular code is a set of trinucleotides allowing the reading frames in genes to be retrieved locally, i.e. anywhere in genes and in particular without start codons, and automatically with a window of few nucleotides. In 1996, a common circular code, called X, was identified in large populations of eukaryotic and prokaryotic genes. Hence, it is believed to be an ancestral structural property of genes. A new computational approach based on comparative genomics is developed to identify essential molecular functions associated with circular codes. It is based on a quantitative and sensitive statistical method (FPTF) to identify three permuted trinucleotide sets in the three frames of genes, a flower automaton algorithm to determine if a trinucleotide set is a circular code or not, and an integrated Gene Ontology and Taxonomy (iGOT) database. By carrying out automatic circular code analyses on a huge number of gene populations where each population is associated with a particular molecular function, it identifies 266 gene populations having circular codes close to X. Surprisingly, their molecular functions include 98% of those covered by the essential genes of the DEG database (Database of Essential Genes). Furthermore, three trinucleotides GTG, AAG and GCG, replacing three trinucleotides of the code X and called "evolutionary" trinucleotides, significantly occur in these 266 gene populations. Finally, a new method developed to analyse and quantify the stability of a set of trinucleotides demonstrates that these evolutionary trinucleotides are associated with a significant increase of the stability of the common circular code X. Indeed, its stability increases from the 1502th rank to the 16th rank after the replacement of the three evolutionary trinucleotides among 9920 possible trinucleotide replacement sets., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A new trinucleotide proposition is proved here and allows all the trinucleotide circular codes on the genetic alphabet to be identified (their numbers and their sets of words). This new class of genetic motifs, i.e. circular codes (or synchronizing genetic motifs), may be involved in the structure and the origin of the genetic code, and in reading frames of genes., (Copyright 2010 Elsevier Ltd. All rights reserved.)

In this paper we present a new computational method leading to the identification of a new property in the plant microRNAs. This property which is based on the circular code information is then used to detect microRNAs in plants. The common C(3) circular code X is a set of 20 trinucleotides identified in the reading frames of both eukaryotic and prokaryotic genes allowing retrieval of any frame in genes, locally anywhere in the three frames (reading frame and its two shifted frames) and automatically with the same window length of 13 nucleotides in each frame. This code X is detected around the beginning of microRNAs. This method based only on the internal structure of genes, i.e. the circular code, allows sensible and precise microRNA site identification in precursor microRNAs with a sliding window of only 14 nucleotides.

The synthesis of several oxyphytosterols is described starting from stigmasterol, the key step being the regioselective hydrogenation of the 22-23 double bond of the latter.

We develop here an analytical evolution model based on a dinucleotide mutation matrix 16 x 16 with six substitution parameters associated with the three types of substitutions in the two dinucleotide sites. It generalizes the previous models based on the nucleotide mutation matrices 4 x 4. It determines at some time t the exact occurrence probabilities of dinucleotides mutating randomly according to these six substitution parameters. Furthermore, several properties and two applications of this model allow to derive 16 evolutionary analytical solutions of dinucleotides and also a dinucleotide phylogenetic distance. Finally, based on this mathematical model, the SED (Stochastic Evolution of Dinucleotides) web server has been developed for deriving evolutionary analytical solutions of dinucleotides.

This paper presents a novel, completely unsupervised fMRI brain mapping method that addresses the three problems of hemodynamic response function (HRF) variability, hemodynamic event timing, and fMRI response non-linearity. Spatial and temporal information are directly taken into account into the core of the activation detection process. In practice, activation detection at voxel v is formulated in terms of temporal alignment between sequences of hemodynamic response onsets (HROs) detected in the fMRI signal at v and in the spatial neighborhood of v, and the input sequence of stimuli or stimulus onsets. Event-related and epoch paradigms are considered. The multiple event sequence alignment problem is solved within the probabilistic framework of hidden Markov multiple event sequence models (HMMESMs), a new class of hidden Markov models. Results obtained on real and synthetic data significantly outperform those obtained with the popular statistical parametric mapping (SPM2) method without requiring any prior definition of the expected activation patterns, the HMMESM mapping approach being completely unsupervised.

We develop here an analytical evolution model based on a trinucleotide mutation matrix 64x64 with nine substitution parameters associated with the three types of substitutions in the three trinucleotide sites and with non-zero elements on its main diagonal. It generalizes the previous models based on the nucleotide mutation matrices 4x4 and the trinucleotide mutation matrices 64x64 with zero elements on its main diagonal. It determines at some time t the exact occurrence probabilities of trinucleotides mutating randomly according to these nine substitution parameters. Furthermore, applications of this model allow to generalize an evolutionary analytical solution of the common circular code of eukaryotes and prokaryotes and also to derive a codon phylogenetic distance.

This paper proposes a comprehensive evaluation of a monomodal B-spline-based non-rigid registration algorithm allowing topology preservation in 3-D. This article is to be considered as the companion of [Noblet, V., Heinrich, C., Heitz, F., Armspach, J.-P., 2005. 3-D deformable image registration: a topology preservation scheme based on hierarchical deformation models and interval analysis optimization. IEEE Transactions on Image Processing, 14 (5), 553-566] where this algorithm, based on the minimization of an objective function, was introduced and detailed. Overall assessment is based on the estimation of synthetic deformation fields, on average brain construction, on atlas-based segmentation and on landmark mapping. The influence of the model parameters is characterized. Comparison between several objective functions is carried out and impact of their symmetrization is pointed out. An original intensity normalization scheme is also introduced, leading to significant improvements of the registration quality. The comparison benchmark is the popular demons algorithm [Thirion, J.-P., 1998. Image matching as a diffusion process: an analogy with Maxwell's demons. Medical Image Analysis, 2 (3), 243-260], that exhibited best results in a recent comparison between several non-rigid 3-D registration methods [Hellier, P., Barillot, C., Corouge, I., Gibaud, B., Le Goualher, G., Collins, D.L., Evans, A., Malandain, G., Ayache, N., Christensen, G.E., Johnson, H.J., 2003. Retrospective evaluation of intersubject brain registration. IEEE Transactions on Medical Imaging, 22 (9), 1120-1130]. The topology preserving B-spline-based method proved to outperform the commonly available ITK implementation of the demons algorithms on many points. Some limits of intensity-based registration methods are also highlighted through this work.

We developed a statistical method that allows each trinucleotide to be associated with a unique frame among the three possible ones in a (protein coding) gene. An extensive gene study in 175 complete bacterial genomes based on this statistical approach resulted in identification of 72 new circular codes. Finding a circular code enables an immediate retrieval of the reading frame locally anywhere in a gene. No knowledge of location of the start codon is required and a short window of only a few nucleotides is sufficient for automatic retrieval. We have therefore developed a factorization method (that explores previously found circular codes) for retrieving the reading frames of bacterial genes. Its principle is new and easy to understand. Neither complex treatment nor specific information on the nucleotide sequences is necessary. Moreover, the method can be used for short regions in nucleotide sequences (less than 25 nucleotides in protein coding genes). Selected additional properties of circular codes and their possible biological consequences are also discussed.

We develop here an analytical evolutionary model based on a trinucleotide mutation matrix 64 x 64 with six substitution parameters associated with the transitions and transversions in the three trinucleotide sites. It generalizes the previous models based on the nucleotide mutation matrices 4 x 4 and the trinucleotide mutation matrix 64 x 64 with three parameters. It determines at some time t the exact occurrence probabilities of trinucleotides mutating randomly according to six substitution parameters. An application of this model allows an evolutionary study of the common circular code COM and the 15 archaeal circular codes X which have been recently identified in several archaeal genomes. The main property of a circular code is the retrieval of the reading frames in genes, both locally, i.e. anywhere in genes and in particular without a start codon, and automatically with a window of a few nucleotides. In genes, the circular code is superimposed on the traditional genetic one. Very unexpectedly, the evolutionary model demonstrates that the archaeal circular codes can derive from the common circular code subjected to random substitutions with particular values for six substitutions parameters. It has a strong correlation with the statistical observations of three archaeal codes in actual genes. Furthermore, the properties of these substitution rates allow proposal of an evolutionary classification of the 15 archaeal codes into three main classes according to this model. In almost all the cases, they agree with the actual degeneracy of the genetic code with substitutions more frequent in the third trinucleotide site and with transitions more frequent that transversions in any trinucleotide site.

Neural stem cells cultured as neurospheres were used to assess the effects of P. notoginseng on the production of neurons and glia. The crude saponins (PNS) and ginsenoside-Rd promote the differentiation of neurospheres into astrocytes. Ginsenoside-Rd increases the production of astrocytes in a dose-dependent manner. On the other hand, both PNS and ginsenoside-Rd induce a weak but significant effect by decreasing the number of neurons. The other ginsenosides do not induce any differentiation on both neurons and astrocytes.

A new statistical method associating each trinucleotide with a frame is developed for identifying circular codes. Its sensibility allows the detection of several circular codes in the (protein coding) genes of archaeal genomes. Several properties of these circular codes are described, in particular the lengths of the minimal windows to retrieve the construction frames, a new definition of a parameter for measuring some probabilities of words generated by the circular codes, and the types of nucleotides in the trinucleotide sites. Some biological consequences are presented in Discussion.