Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

SynthBuilder and Frankenstein: Tools for the creation of musical physical models

Presented at 3rd International Conference on Auditory Display (ICAD), Palo Alto, California, November 4-6, 1996.SynthBuilder is a user-extensible, object-oriented, NEXTSTEP Music Kit application for interactive real-time design and performance of synthesizer patches (especially physical models) (Jaffe & Smith, 1983; Smith, 1987). Patches are represented by networks consisting of digital signal processing elements called unit generators and MIDI event elements called note filters and note generators. The Frankenstein box is a multi-DSP compute engine that was developed as a research platform (Putnam, 1996). The box communicates with an x86 host via an ISA interface card that resides in the host computer. Frankenstein currently contains 8 Motorola 56002 Evaluation Modules (EVMs), and it can be scaled to an additional 8 EVMs for a 16 EVM total. The outputs of EVMs can also be sent to an external mixer

Celebrating the Social in Soccer: Spectators’ Experiences of the Forgotten (Blind) Football World Cup

Sporting spaces draw together distinct social assortments. Football (in various forms), for example, generates specific types of spectators and spectator behaviours. Cognizant of this work, our paper examines the 2010 World Blind Football Championships (WBFC) and its spectatorship. We conducted semi-structured interviews, orientated around perceptions of disability/disability sport, with 285 spectators. The thrust of our paper is that the event affords spectators opportunities to better understand, appreciate and engage with the experiences of athletes with a disability. We argue that the unique context of blind football competitions (characterized here as an unthreatening, convivial, often familial-like, and somewhat parochial space) resulted in positive spectator experiences. We conclude that within the framework of bridging social capital, this unique sporting space afforded the creation of relationships between the athletes (and the sport) and the spectators, two groups previously separated by social distance

Solution structure and dynamics of a calcium binding epidermal growth factor-like domain pair from the neonatal region of human fibrillin-1

Fibrillin-1 is a mosaic protein mainly composed of 43 calcium binding epidermal growth factor-like (cbEGF) domains arranged as multiple, tandem repeats. Mutations within the fibrillin-1 gene cause Marfan syndrome (MFS), a heritable disease of connective tissue. More than 60% of MFS-causing mutations identified are localized to cbEGFs, emphasizing that the native properties of these domains are critical for fibrillin-1 function. The cbEGF12-13 domain pair is within the longest run of cbEGFs, and many mutations that cluster in this region are associated with severe, neonatal MFS. The NMR solution structure of Ca2+-loaded cbEGF12-13 exhibits a near-linear, rod-like arrangement of domains. This observation supports the hypothesis that all fibrillin-1 (cb)EGF-cbEGF pairs, characterized by a single interdomain linker residue, possess this rod-like structure. The domain arrangement of cbEGF12-13 is stabilized by additional interdomain packing interactions to those observed for cbEGF32-33, which may help to explain the previously reported higher calcium binding affinity of cbEGF13. Based on this structure, a model of cbEGF11-15 that encompasses all known neonatal MFS missense mutations has highlighted a potential binding region. Backbone dynamics data confirm the extended structure of cbEGF12-13 and lend support to the hypothesis that a correlation exists between backbone flexibility and cbEGF domain calcium affinity. These results provide important insight into the potential consequences of MFS-associated mutations for the assembly and biomechanical properties of connective tissue microfibrils. <br/