We present a domain-independent model of hierarchical software system design and construction thal is based on interchangeable software components and large-scale reuse. The model unifies the conceptualizations of two independent projects, Genesis and Avoca, that are successful examples of software component/building-block technologies and domain modeling. Buildingblock technologies exploit large-scale reuse, rely on open architecture software, and elevate the granularity of programming to the subsystem level. Domain modeling formalizes the similarities and differences among systems of a domain. We believe our model is a blueprint for achieving software component technologies in many domains.

The m-Bop protein encoded by the mouse Bop gene is strongly expressed in heart and skeletal muscle, and recent studies with Bop knockout mice have demonstrated that m-Bop is essential for cardiogenesis in vivo and can act as a HDAC-dependent repressor in vitro. In the present studies, m-Bop was observed to interact with skNAC, a reported transcriptional activator specific to heart and skeletal muscle. The amino-terminal S region of the split S-ET domain of m-Bop as well as the MYND domain were required for interaction with skNAC in both the two-hybrid system and in coimmunoprecipitation experiments from cultured mammalian cells. As shown previously for interaction of the MYND domain-containing transcriptional corepressor, BS69, with several viral and cellular oncoproteins, a PXLXP motif in skNAC was required for interaction with mBop. Similar kinetics of induction and localization of m-Bop and skNAC during the induction of myogenesis in cultured C2C12 cells suggests a possible associated role for these proteins during this process.The control of skeletal and cardiac maturation is ordered in a complex cascade of transcriptional activation and repression. The MyoD and MEF2 families of transcription factors dictate important developmental events that result in the formation of mature skeletal muscle. The MyoD family is comprised of the basic helix-loop-helix proteins MyoD, Myf5, MRF4, and myogenin. These myogenic regulators form heterodimers with the ubiquitous basic helix-loop-helix E proteins that subsequently activate key elements needed for the myogenic program (1). The MEF2 family is defined by the MADS domain and consists of MEF2A, MEF2B, MEF2C, and MEF2D. Members of the MEF2 family are expressed in tissues besides skeletal muscle including cardiac tissue, neurons, and T cells (2). Together, the MyoD and MEF2 families cooperate directly and indirectly to transduce the requisite signals for proper skeletal muscle formation.The discovery of chamber-specific transcription factors, such as the Hand1 and Hand2 proteins, has revealed the complex nature of cardiac transcriptional regulation (3). The list of genes that correspond to specific cardiac defects continues to grow, whereas the molecular nature of these defects remains largely elusive (4). To further understand the molecular underpinnings of cardiac development, it is critical to identify the relationships of transcriptional regulators shown to be important in cardiac morphogenesis.The Bop gene encodes distinct proteins expressed in skeletal and cardiac muscle, as well as in cytotoxic T lymphocytes. The Bop proteins found in skeletal muscle (m-Bop) and cytotoxic T lymphocytes (t-Bop) are identical over 90% of their primary amino acid sequence, differing only at their extreme amino terminus (5). Bop contains the evolutionarily conserved MYND and SET domains found in transcriptional regulators linked to development, chromatin stability, and cancer. The MYND domains in the transcriptional regulators ETO (MTG8) and BS69 function as protein-protein interaction d...

Furin plays a crucial role in embryogenesis and homeostasis and in diseases such as Alzheimer's disease, cancer, and viral and bacterial infections. Thus, inhibition of furin may provide a feasible and promising approach for therapeutic intervention of furin-mediated disease mechanisms. Here, we report on a class of small molecule furin inhibitors based on 2,5-dideoxystreptamine. Derivatization of 2,5-dideoxystreptamine by the addition of guanidinylated aryl groups yielded a set of furin inhibitors with nanomolar range potency against furin when assayed in a biochemical cleavage assay. Moreover, a subset of these furin inhibitors protected RAW 264.7 macrophage cells from toxicity caused by furin-dependent processing of anthrax protective antigen. These inhibitors were found to behave as competitive inhibitors of furin and to be relatively specific for furin. Molecular modeling revealed that these inhibitors may target the active site of furin as they showed site occupancy similar to the alkylating inhibitor decanoyl-Arg-Val-LysArg-CH 2Cl. The compounds presented here are bona fide synthetic small molecule furin inhibitors that exhibit potency in the nanomolar range, suggesting that they may serve as valuable tools for studying furin action and potential therapeutics agents for furindependent diseases.serine endoprotease ͉ prohormone ͉ proprotein convertase F urin is a membrane-anchored, calcium-dependent serine endoprotease and is expressed in all tissues and cell lines examined (1-3). It is the first and, so far, the best-characterized member of the mammalian subtilisin-like family of prohormone/proprotein convertases (PCs), which convert precursors of many secreted proteins and peptide hormones into their biologically active forms (1-3). Furin is predominantly localized in the trans-Golgi network and cycles between this compartment, the cell surface, and the endosomes (2, 4). Hence, furin is able to access and efficiently process a diverse spectrum of substrates including growth factors, receptors, serum proteins, matrix metalloproteinases, viral envelope glycoproteins, and bacterial toxins, typically at sites with the consensus sequence Arg-Xaa-Lys/Arg-Arg 2 (2).Although furin plays an essential role in embryogenesis and homeostasis, this endoprotease has also been implicated in the neurodegeneration associated with Alzheimer's disease, and tumor metastasis and the activation and virulence of many bacterial and viral pathogens (2). It has been demonstrated that furin inhibitors modulate tumor growth (5) and attenuate the toxicity of anthrax (6) and Pseudomonas aeruginosa (7) toxins and cytomegalovirus (8) in cell culture and animal models. Therefore, furin inhibitors hold great promise as potential therapeutic agents for treating furinmediated diseases and viral and bacterial infections, particularly for short-term therapy.To date, most furin inhibitors reported in the literature have been proteins (9-19) or peptides (20-24), which show excellent potency against furin, and largely mimic the substrate in bindi...

Abstract. The Diffie-Hellman key exchange algorithm can be implemented using the group of points on an elliptic curve over the field F2m. A software version of this using n = 155 can be optimized to achieve computation rates that are slightly faster than non-elliptic curve versions with a similar level of security. The fast computation of reciprocals in F2rn is the key to the highly efficient implementation described here.

Network software is a critical component of any distributed system. Because of its complexity, network software is commonly layered into a hierarchy of protocols, or more generally, into a protocol graph . Typical protocol graphs—including those standardized in the ISO and TCP/IP network architectures—share three important properties; the protocol graph is simple, the nodes of the graph (protocols) encapsulate complex functionality, and the topology of the graph is relatively static. This paper describes a new way to organize network software that differs from conventional architectures in all three of these properties. In our approach, the protocol graph is complex, individual protocols encapsulate a single function, and the topology of the graph is dynamic. The main contribution of this paper is to describe the ideas behind our new architecture, illustrate the advantages of using the architecture, and demonstrate that the architecture results in efficient network software.