Evolution of distinct EGF domains with specific functions

EGF domains are extracellular protein modules cross-linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three-disulfides, human EGF-like (hEGF) domains and complement C1r-like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C-termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern-based method represents a significant advancement over the currently available sequence detection techniques. We re-annotated EGF sequences in the latest release of Swiss-Prot looking for functional relationships that might correlate with EGF type. We show that important post-translational modifications of three-disulfide EGFs, including unusual forms of glycosylation and post-translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three-disulfide bonds and comparison to laminin and integrin-like EGF domains with an additional interdomain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four-disulfide ancestor by selective loss of different cysteine residues.

Independent functions of yeast Pcf11p in pre-mRNA 3´ end processing and in transcription termination

Pcf11p, an essential subunit of the yeast cleavage factor IA, is required for pre-mRNA 3' end processing, binds to the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II) and is involved in transcription termination. We show that the conserved CTD interaction domain (CID) of Pcf11p is essential for cell viability. Interestingly, the CTD binding and 3' end processing activities of Pcf11p can be functionally uncoupled from each other and provided by distinct Pcf11p fragments in trans. Impaired CTD binding did not affect the 3' end processing activity of Pcf11p and a deficiency of Pcf11p in 3' end processing did not prevent CTD binding. Transcriptional run-on analysis with the CYC1 gene revealed that loss of cleavage activity did not correlate with a defect in transcription termination, whereas loss of CTD binding did. We conclude that Pcf11p is a bifunctional protein and that transcript cleavage is not an obligatory step prior to RNAP II termination.

Functions for S. cerevisiae Swd2p in 3' end formation of specific mRNAs and snoRNAs and global histone 3 lysine 4 methylation

The Saccharomyces cerevisiae WD-40 repeat protein Swd2p associates with two functionally distinct multiprotein complexes: the cleavage and polyadenylation factor (CPF) that is involved in pre-mRNA and snoRNA 3′ end formation and the SET1 complex (SET1C) that methylates histone 3 lysine 4. Based on bioinformatic analysis we predict a seven-bladed β-propeller structure for Swd2p proteins. Northern, transcriptional run-on and in vitro 3′ end cleavage analyses suggest that temperature sensitive swd2 strains were defective in 3′ end formation of specific mRNAs and snoRNAs. Protein–protein interaction studies support a role for Swd2p in the assembly of 3′ end formation complexes. Furthermore, histone 3 lysine 4 di-and tri-methylation were adversely affected and telomeres were shortened in swd2 mutants. Underaccumulation of the Set1p methyltransferase accounts for the observed loss of SET1C activity and suggests a requirement for Swd2p for the stability or assembly of this complex. We also provide evidence that the roles of Swd2p as component of CPF and SET1C are functionally independent. Taken together, our results establish a dual requirement for Swd2p in 3′ end formation and histone tail modification.

Penalty functions over a cartesian product of lattices

In this work we present the concept of penalty function over a Cartesian product of lattices. To build these mappings, we make use of restricted dissimilarity functions and distances between fuzzy sets. We also present an algorithm that extends the weighted voting method for a fuzzy preference relation.

Restricted dissimilarity functions and penalty functions

In this work we introduce the definition of restricted dissimilarity functions and we link it with some other notions, such as metrics. In particular, we also show how restricted dissimilarity functions can be used to build penalty functions.

Brain MRI thresholding using incomparability and overlap functions

In this work we present a new image thresholding algorithm for the segmentation of MRI brain images into two classes: gray matter and white matter. The proposed algorithm is based on the concept of incomparability proposed by Fodor and Roubens for fuzzy preference relations. We test our algorithm for local and global segmentation of brain images. We proof that global segmentation performs better results than local segmentation and improves the results obtained by other thresholding algorithm.

Efficient subwindow search with submodular score functions

Subwindow search aims to find the optimal subimage which maximizes the score function of an object to be detected. After the development of the branch and bound (B&B) method called Efficient Subwindow Search (ESS), several algorithms (IESS [2], AESS [2], ARCS [3]) have been proposed to improve the performance of ESS. For nn images, IESS's time complexity is bounded by O(n³) which is better than ESS, but only applicable to linear score functions. Other work shows that Monge properties can hold in subwindow search and can be used to speed up the search to O(n³), but only applies to certain types of score functions. In this paper we explore the connection between submodular functions and the Monge property, and prove that sub-modular score functions can be used to achieve O(n³) time complexity for object detection. The time complexity can be further improved to be sub-cubic by applying B&B methods on row interval only, when the score function has a multivariate submodular bound function. Conditions for sub-modularity of common non-linear score functions and multivariate submodularity of their bound functions are also provided, and experiments are provided to compare the proposed approach against ESS and ARCS for object detection with some nonlinear score functions.

Hierarchical topical segmentation in instructional films based on cinematic expressive functions

In this paper, we propose a novel solution for segmenting an instructional video into hierarchical topical sections. Incorporating the knowledge of education-oriented film theory with our previous study of expressive functions namely the content density and the thematic functions, we develop an algorithm to effectively structuralize an instructional video into a two-tiered hierarchy of topical sections at the main and sub-topic levels. Our experimental results on a set of ten industrial instructional videos demonstrate the validity of the detection scheme.

On the extraction of thematic and dramatic functions of content in educational videos

In this paper, we propose novel computational models for the extraction of high level expressive constructs related to, namely thematic and dramatic functions of the content shown in educational and training videos. Drawing on the existing knowledge of film theory, and media production rules and conventions used by the filmmakers. we hypothesize key aesthetic elements contributing to convey these functions of the content. Computational models to extract them are then formulated and their performance evaluated on a set of ten educational and training videos is presented.