Decoding Single Molecule Time Traces with Dynamic Disorder

Single molecule time trajectories of biomolecules provide glimpses into complex folding landscapes that are difficult to visualize using conventional ensemble measurements. Recent experiments and theoretical analyses have highlighted dynamic disorder in certain classes of biomolecules, whose dynamic pattern of conformational transitions is affected by slower transition dynamics of internal state hidden in a low dimensional projection. A systematic means to analyze such data is, however, currently not well developed. Here we report a new algorithm - Variational Bayes-double chain Markov model (VB-DCMM) - to analyze single molecule time trajectories that display dynamic disorder. The proposed analysis employing VB-DCMM allows us to detect the presence of dynamic disorder, if any, in each trajectory, identify the number of internal states, and estimate transition rates between the internal states as well as the rates of conformational transition within each internal state. Applying VB-DCMM algorithm to single molecule FRET data of H-DNA in 100 mM-Na$^+$ solution, followed by data clustering, we show that at least 6 kinetic paths linking 4 distinct internal states are required to correctly interpret the duplex-triplex transitions of H-DNA

Construction of biorthogonal wavelet vectors

AbstractThe construction of all possible biorthogonal wavelet vectors corresponding to a given biorthogonal scaling vector may not be easy as that of biorthogonal uniwavelets. In this paper, we give some theorems about the construction of biorthogonal wavelet vectors, which is followed by simple computations for constructing all parametrized biorthogonal wavelet vectors supported in [-1,1]. This approach is also suitable for the case of compactly supported orthogonal uniwavelet. Moreover, we give examples parametrizing all biorthogonal wavelet vectors corresponding to well known biorthogonal scaling vectors

Compensation of Outside Directors: An Empirical Analysis of Economic Determinants

Little is known about the economic environments and determinants of the compensation arrangements for outside board members. As delegated monitors of corporate management, board members act as shareholders' agents. Thus, a potential for misaligned interests exists, requiring in turn incentive arrangements that are incentive-compatible and individually rational. We study the economic determinants of both the levels and mix of compensation for outside board members. We also examine the effects of the existence of a director pension plan on the relation between director compensation and the hypothesized determinants. In sum, and contrary to criticism that the board of directors is often a passive, ineffective entity that dislikes conflict with incumbent management, we find that board compensation is structured to mitigate agency problems inherent in firms whose management control is separated from ownership

The complete mitochondrial genome of the sea spider Achelia bituberculata (Pycnogonida, Ammotheidae): arthropod ground pattern of gene arrangement

<p>Abstract</p> <p>Background</p> <p>The phylogenetic position of pycnogonids is a long-standing and controversial issue in arthropod phylogeny. This controversy has recently been rekindled by differences in the conclusions based on neuroanatomical data concerning the chelifore and the patterns of <it>Hox </it>expression. The mitochondrial genome of a sea spider, <it>Nymphon gracile </it>(Pycnogonida, Nymphonidae), was recently reported in an attempt to address this issue. However, <it>N. gracile </it>appears to be a long-branch taxon on the phylogenetic tree and exhibits a number of peculiar features, such as 10 tRNA translocations and even an inversion of several protein-coding genes. Sequences of other pycnogonid mitochondrial genomes are needed if the position of pycnogonids is to be elucidated on this basis.</p> <p>Results</p> <p>The complete mitochondrial genome (15,474 bp) of a sea spider (<it>Achelia bituberculata</it>) belonging to the family Ammotheidae, which combines a number of anatomical features considered plesiomorphic with respect to other pycnogonids, was sequenced and characterized. The genome organization shows the features typical of most metazoan animal genomes (37 tightly-packed genes). The overall gene arrangement is completely identical to the arthropod ground pattern, with one exception: the position of the <it>trnQ </it>gene between the <it>rrnS </it>gene and the control region. Maximum likelihood and Bayesian inference trees inferred from the amino acid sequences of mitochondrial protein-coding genes consistently indicate that the pycnogonids (<it>A. bituberculata </it>and <it>N. gracile</it>) may be closely related to the clade of Acari and Araneae.</p> <p>Conclusion</p> <p>The complete mitochondrial genome sequence of <it>A. bituberculata </it>(Family Ammotheidae) and the previously-reported partial sequence of <it>Endeis spinosa </it>show the gene arrangement patterns typical of arthropods (<it>Limulus</it>-like), but they differ markedly from that of <it>N. gracile</it>. Phylogenetic analyses based on mitochondrial protein-coding genes showed that Pycnogonida may be authentic arachnids (= aquatic arachnids) within Chelicerata <it>sensu lato</it>, as indicated by the name 'sea spider,' and suggest that the Cormogonida theory – that the pycnogonids are a sister group of all other arthropods – should be rejected. However, in view of the relatively weak node confidence, strand-biased nucleotide composition and long-branch attraction artifact, further more intensive studies seem necessary to resolve the exact position of the pycnogonids.</p

SNP@Ethnos: a database of ethnically variant single-nucleotide polymorphisms

Inherited genetic variation plays a critical but largely uncharacterized role in human differentiation. The completion of the International HapMap Project makes it possible to identify loci that may cause human differentiation. We have devised an approach to find such ethnically variant single-nucleotide polymorphisms (ESNPs) from the genotype profile of the populations included in the International HapMap database. We selected ESNPs using the nearest shrunken centroid method (NSCM), and performed multiple tests for genetic heterogeneity and frequency spectrum on genes having ESNPs. The function and disease association of the selected SNPs were also annotated. This resulted in the identification of 100 736 SNPs that appeared uniquely in each ethnic group. Of these SNPs, 1009 were within disease-associated genes, and 85 were predicted as damaging using the Sorting Intolerant From Tolerant system. This study resulted in the creation of the SNP@Ethnos database, which is designed to make this type of detailed genetic variation approach available to a wider range of researchers. SNP@Ethnos is a public database of ESNPs with annotation information that currently contains 100 736 ESNPs from 10 138 genes, and can be accessed at and or directly at