Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from similar to 250 kb to similar to 2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2.

Template-based quadrilateral mesh generation from imaging data

This paper describes a novel template-based meshing approach for generating good quality quadrilateral meshes from 2D digital images. This approach builds upon an existing image-based mesh generation technique called Imeshp, which enables us to create a segmented triangle mesh from an image without the need for an image segmentation step. Our approach generates a quadrilateral mesh using an indirect scheme, which converts the segmented triangle mesh created by the initial steps of the Imesh technique into a quadrilateral one. The triangle-to-quadrilateral conversion makes use of template meshes of triangles. To ensure good element quality, the conversion step is followed by a smoothing step, which is based on a new optimization-based procedure. We show several examples of meshes generated by our approach, and present a thorough experimental evaluation of the quality of the meshes given as examples.

Wavelet-based dynamic time warping

Dynamic Time Warping (DTW), a pattern matching technique traditionally used for restricted vocabulary speech recognition, is based on a temporal alignment of the input signal with the template models. The principal drawback of DTW is its high computational cost as the lengths of the signals increase. This paper shows extended results over our previously published conference paper, which introduces an optimized version of the DTW I hat is based on the Discrete Wavelet Transform (DWT). (C) 2008 Elsevier B.V. All rights reserved.

Structural matching of 2D electrophoresis gels using deformed graphs

2D electrophoresis is a well-known method for protein separation which is extremely useful in the field of proteomics. Each spot in the image represents a protein accumulation and the goal is to perform a differential analysis between pairs of images to study changes in protein content. It is thus necessary to register two images by finding spot correspondences. Although it may seem a simple task, generally, the manual processing of this kind of images is very cumbersome, especially when strong variations between corresponding sets of spots are expected (e.g. strong non-linear deformations and outliers). In order to solve this problem, this paper proposes a new quadratic assignment formulation together with a correspondence estimation algorithm based on graph matching which takes into account the structural information between the detected spots. Each image is represented by a graph and the task is to find a maximum common subgraph. Successful experimental results using real data are presented, including an extensive comparative performance evaluation with ground-truth data. (C) 2010 Elsevier B.V. All rights reserved.

Design and use of mobile technology in distance language education : Matching learning practices with technologies-in-practice

This thesis focuses on the adaptation of formal education to people’s technology- use patterns, theirtechnology-in-practice, where the ubiquitous use of mobile technologies is central. The research question is: How can language learning practices occuring in informal learning environments be effectively integrated with formal education through the use of mobile technology? The study investigates the technical, pedagogical, social and cultural challenges involved in a design science approach. The thesis consists of four studies. The first study systematises MALL (mobile-assisted language learning) research. The second investigates Swedish and Chinese students’ attitudes towards the use of mobile technology in education. The third examines students’ use of technology in an online language course, with a specific focus on their learning practices in informal learning contexts and their understanding of how this use guides their learning. Based on the findings, a specifically designed MALL application was built and used in two courses. Study four analyses the app use in terms of students’ perceived level of self-regulation and structuration. The studies show that technology itself plays a very important role in reshaping peoples’ attitudes and that new learning methods are coconstructed in a sociotechnical system. Technology’s influence on student practices is equally strong across borders. Students’ established technologies-in-practice guide the ways they approach learning. Hence, designing effective online distance education involves three interrelated elements: technology, information, and social arrangements. This thesis contributes to mobile learning research by offering empirically and theoretically grounded insights that shift the focus from technology design to design of information systems.