We have constructed a database of alternatively spliced protein forms (ASP), consisting of 13,384 protein isoform sequences of 4422 human genes (www.bioinformatics.ucla.edu/ASP). We identified fifty protein domain types that were selectively removed by alternative splicing at much higher frequencies than average (p-value < 0.01). These include many well-known protein-interaction domains (e.g., KRAB; ankyrin repeats; Kelch) including some that have been previously shown to be regulated functionally by alternative splicing (e.g., collagen domain). We present a number of novel examples (Kruppel transcription factors; Pbx2; Enc1) from the ASP database, illustrating how this pattern of alternative splicing changes the structure of a biological pathway, by redirecting protein interaction networks at key switch points. Our bioinformatics analysis indicates that a major impact of alternative splicing is removal of protein-protein interaction domains that mediate key linkages in protein interaction networks. ASP expands the available dataset of human alternatively spliced protein forms from 1989 human genes (SwissProt release 42) to 5413 (nonredundant set, ASP + SwissProt), a nearly 3-fold increase. ASP will enhance the existing pool of protein sequences that are searched by mass spectroscopy software during the identification of peptide fragments.
One goal of wearable computing is to create digital devices that are as easy to don and as comfortable to wear as common articles of clothing such as blouses, pants, and belts. New forms of woven materials such as conductive webbings, which incorporate durable electrical conductors directly into the matrix of the weave, offer exciting possibilites for closely integrating digital electronics with conventional clothing. However, many practical obstacles hinder the adoption of these materials, not the least being a lack of reliable electrical connectors for the interconnection of conventional electronics with conductive fabrics. We present a simple and workable design for just such connectors and demonstrate how a commonplace article of clothing -suspenders -can be transformed into an effective power bus and data network for wearable digital devices. Both the power bus and the data network are described in detail, including the mechanics of attachment and an outline of the network protocols. The techniques illustrated here can be readily applied to other articles of clothing and accessories.
Seventeen years after its initial publication at ICSE 2000, the Representational State Transfer (REST) architectural style continues to hold significance as both a guide for understanding how the World Wide Web is designed to work and an example of how principled design, through the application of architectural styles, can impact the development and understanding of large-scale software architecture. However, REST has also become an industry buzzword: frequently abused to suit a particular argument, confused with the general notion of using HTTP, and denigrated for not being more like a programming methodology or implementation framework. In this paper, we chart the history, evolution, and shortcomings of REST, as well as several related architectural styles that it inspired, from the perspective of a chain of doctoral dissertations produced by the University of California's Institute for Software Research at UC Irvine. These successive theses share a common theme: extending the insights of REST to new domains and, in their own way, exploring the boundary of software engineering as it applies to decentralized software architectures and architectural design. We conclude with discussion of the circumstances, environment, and organizational characteristics that gave rise to this body of work.
Visual programming research has largely focused on the issues of visual programming-in-the-small. However, entirely different concerns arise when one is programmingin-the-large. We present a visual software engineering environment that allows users to construct visually programs consisting of hierarchically organized networks of components that process streams of arbitrary objects. We discuss the problems that occur when trying to construct systems consisting of thousands of interconnected components, examine how this environment deals with some of the problems specific to visual programming-in-the-large, and show why our initial solutions failed to scale successfully. Finally, we argue that a single visual mechanism called "zooming" addresses these scaling problems and, when suitably augmented, can also support automatic component discovery and intelligent error correction.
Decentralized systems are systems-of-systems whose services are governed by two or more separate organizations under distinct spheres of authority. Coordinated evolution of the various elements of a decentralized system may be difficult, if not impossible, as individual organizations evolve their service offerings in response to organizationand service-specific pressures, including market demand, technology, competitive and cooperative interests, and funding. Consequently, decentralized services offer unique challenges for evolution and adaptation that reach well beyond any one single organizational boundary. However, client-driven service customization and tailoring is a powerful tool for meeting conflicting, independent client demands in an environment where disorderly and uneven service evolution predominates. To this end, we contribute an architectural style, COmputAtional State Transfer (COAST), designed to provide extensive, safe, and secure client-directed customization of decentralized services. COAST combines mechanisms from software architecture, cryptography, security, and programming languages, granting application architects flexible provisioning of their core services and assets while protecting those services and assets from attack and misuse.
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