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Transforming growth factor-beta (TGFbeta) family members regulate many developmental and pathological events through Smad transcriptional modulators. How nuclear accumulation of Smad is coupled to the transcriptional machinery is poorly understood. Here we demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds(More)
We have used directed evolution to construct IL-2 mutants that bind the IL-2 alpha receptor subunit (IL-2Ralpha, CD25) with affinities comparable to that of the IL-15-IL-15 alpha receptor subunit (IL-15Ralpha) interaction. T cells proliferate for up to 6 days following a 30 minute incubation with these IL-2 mutants, which may lead to potential applications(More)
Most undergraduate curriculums in CS include at least a one semester study of data base management systems. In this paper, we take a closer look at a DBMS course we have offered recently and elaborate on a world wide web based database project in this course; it integrates a number of ideas not only from within DBMS but across other CS areas. We discuss the(More)
Complexity in the spatial organization of human embryonic stem cell (hESC) cultures creates heterogeneous microenvironments (niches) that influence hESC fate. This study demonstrates that the rate and trajectory of hESC differentiation can be controlled by engineering hESC niche properties. Niche size and composition regulate the balance between(More)
Embryonic stem cells (ESCs) are culture-adapted pluripotent cells derived from the inner cell mass of the blastocyst-stage embryo. ESCs provide unique opportunities to study the molecular basis of the process of differentiation that gives rise to all the somatic cell types of the body, including cells of the cardiac lineages. Many protocols have been(More)
Functional genomics and proteomics are identifying many potential drug targets for novel therapeutic proteins, and both rational and combinatorial protein engineering methods are available for creating drug candidates. A central challenge is the definition of the most appropriate design criteria, which will benefit critically from computational kinetic(More)
We have shown that highly stable binding proteins for a wide spectrum of targets can be generated through mutagenesis of the Sso7d protein from the hyperthermophilic archaeon Sulfolobus solfataricus. Sso7d is a small (~7 kDa, 63 amino acids) DNA-binding protein that lacks cysteine residues and has a melting temperature of nearly 100 °C. We generated a(More)
We have engineered pH sensitive binding proteins for the Fc portion of human immunoglobulin G (hIgG) (hFc) using two different strategies - histidine scanning and random mutagenesis. We obtained an hFc-binding protein, Sso7d-hFc, through mutagenesis of the Sso7d protein from the hyperthermophilic archaeon Sulfolobus solfataricus; Sso7d-hFc was isolated from(More)
Binding proteins are typically isolated from combinatorial libraries of scaffold proteins using one of the many library screening tools available, such as phage display, yeast surface display or mRNA display. A key principle underlying these screening technologies is the establishment of a link between each unique mutant protein and its corresponding(More)
Cyclic peptides are attractive candidates for synthetic affinity ligands due to their favorable properties, such as resistance to proteolysis, and higher affinity and specificity relative to linear peptides. Here we describe the discovery, synthesis and characterization of novel cyclic peptide affinity ligands that bind the Fc portion of human(More)