Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model

We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.     

Systemic classification of concern-based design methods in the context of enterprise architecture

Enterprise Architecture (EA) is a relatively new domain that is rapidly developing. “The primary reason for developing EA is to support business by providing the fundamental technology and process structure for an IT strategy” [TOGAF]. EA models have to model enterprises facets that span from marketing to IT. As a result, EA models tend to become large. Large EA models create a problem for model management. Concern-based design methods (CBDMs) aim to solve this problem by considering EA models as a composition of smaller, manageable parts—concerns. There are dozens of different CBDMs that can be used in the context of EA: from very generic methods to specific methods for business modeling or IT implementations. This variety of methods can cause two problems for those who develop and use innovative CBDMs in the field of Enterprise Architecture (EA). The first problem is to choose specific CBDMs that can be used in a given EA methodology: this is a problem for researchers who develop their own EA methodology. The second problem is to find similar methods (with the same problem domain or with similar frameworks) in order to make a comparative analysis with these methods: this is a problem of researchers who develop their own CBDMs related to a specific problem domain in EA (such as business process modeling or aspect oriented programming). We aim to address both of these problems by means of a definition of generic Requirements for CBDMs based on the system inquiry. We use these requirements to classify twenty CBDMs in the context of EA. We conclude with a short discussion about trends that we have observed in the field of concern-based design and modeling.     

The OECD software tool for screening chemicals for persistence and long-range transport potential

We present the software implementation of The OECD P_OV & LRTP Screening Tool (The Tool) that is used to assess the environmental hazard of organic chemicals using metrics of overall persistence (P_OV) and long-range transport potential (LRTP). The Tool is designed to support decision making for chemical management and includes features that are recommended by the Organization for Economic Cooperation and Development (OECD) expert group on multimedia modeling. The Tool is useful for screening the environmental hazard potential of non-ionizing organic chemicals whose environmental partitioning can be described by absorptive capacities of environmental media estimated from partitioning between air, water and octanol in the laboratory. The software includes data storage functionality, and a user interface that is designed to facilitate simple data input and straightforward interpretation of the model results. The effect of uncertainties in input properties describing chemicals can be assessed with a Monte Carlo analysis. The software is evaluated and illustrated by comparing results from The Tool with those from other models and by evaluating four substances that are candidates for regulation or ban under the Stockholm Convention on Persistent Organic Pollutants.     

Computing Fibers: A Novel Fiber for Intelligent Fabrics?

This communication describes a possible path for transition from a wearable computer to a fiber computer in which digital processing power is integrated directly into textiles via circuits on individual fibers. Three different classes of computing fiber substrate (active, passive, and intermediate) are discussed and some technologies for their manufacture are reviewed. It is shown here that with two of these techniques it is possible to develop new substrates for the semiconductor industry. Using an silicon‐on‐insulator (SOI) process, polycrystalline silicon fibers with a length of 42 mm have been successfully produced at NMRC in Ireland. These fibers are 35 μm wide and 1 μm thick. Silicon carbide (SiC) and silicon dioxide (SiO₂) endless fibers (subsequently cut in to 20 cm lengths) have also been produced by extrusion. After sintering, this method yielded polycrystalline SiC fibers and pure amorphous SiO₂ glass fibers. For many future applications, fiber computing appears to be a possible key to success. The computing power offered by such fibers may be combined with additional in‐ and output functions by weaving fiber‐based sensors and piezoelectric materials into textiles.     

T cell receptor restriction of diabetogenic autoimmune NOD T cells

Restricted use of T cell receptor (TCR) gene segments is characteristic of several induced autoimmune disease models. TCR sequences have previously been unavailable for pathogenic T cells which react with a defined autoantigen in a spontaneous autoimmune disease. The majority of T cell clones, derived from islets of NOD mice which spontaneously develop type I diabetes, react with insulin peptide B-(9-23). We have sequenced the alpha and beta chains of TCRs from these B-(9-23)-reactive T cell clones. No TCR beta chain restriction was found. In contrast, the clones (10 of 13) used V alpha13 coupled with one of two homologous J alpha segments (J alpha45 or J alpha34 in 8 of 13 clones). Furthermore, 9 of 10 of the V alpha13 segments are a novel NOD sequence that we have tentatively termed V alpha13.3. This dramatic alpha chain restriction, similar to the beta chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therapy.     

A simple envelope detector

The use of integration and differentiation as Hilbert transformers for envelope detection is considered. The resulting detectors are causal and do not require exact knowledge of carrier phase or frequency. The method requires square and square root operations, but no multiplication. An upper bound is established for magnitude error