A model of defiance : Reimaging the comparative analysis of concealed discourse in text

This paper proposes that texts produced in diverse oral-traditional environments exhibit similarities in their disguise of subversion, particularly social or political resistance to the status quo. The disguise used in a particular text reflects the relationship between the text and its referents, or the cultural environment in which the text is produced and used. Cross-textual similarities reflect the similar processes used to disguise subversive ideas. This paper explores the following questions: 1) How might a particular text have been used to disguise resistance to the dominant hegemony? 2) What is the nature of that resistance as it is presented in the text? 3) What comparisons might we find among textual disguises of resistance from various literatures?Not

Quantifying biogenic bias in screening libraries.

In lead discovery, libraries of 10(6) molecules are screened for biological activity. Given the over 10(60) drug-like molecules thought possible, such screens might never succeed. The fact that they do, even occasionally, implies a biased selection of library molecules. We have developed a method to quantify the bias in screening libraries toward biogenic molecules. With this approach, we consider what is missing from screening libraries and how they can be optimized

Synaptic MAGUK multimer formation is mediated by PDZ domains and promoted by ligand binding

To examine the scaffolding properties of PSD-95, we have taken advantage of established ligand/PDZ domain interactions and developed a cell-based assay for investigating protein complex formation. This assay enables quantitative analysis of PDZ domain-mediated protein clustering using bimolecular fluorescence complementation (BiFC). Two nonfluorescent halves of EYFP were fused to C-terminal PDZ ligand sequences to generate probes that sense for PDZ domain binding grooves of adjacent (interacting) molecules. When these probes are brought into proximity by the PDZ domains of a multiprotein scaffold, a functional fluorescent EYFP molecule can be detected. We have used this system to examine the properties of selected PSD-95 variants and thereby delineated regions of importance for PSD-95 complex formation. Further analysis led to the finding that PSD-95 multimerization is PDZ domain-mediated and promoted by ligand binding

Neighbours

After the Berlin Wall fell, thousands of people who had been unable to travel flooded West. Some returned, others abandoned their homes and never looked back. Today, many houses are still boarded up, a reminder of the divided city and the scars of recent memory that have not fully healed

The Chemical Basis of Pharmacology

ABSTRACT: Molecular biology now dominates pharmacology so thoroughly that it is difficult to recall that only a generation ago the field was very different. To understand drug action today, we characterize the targets through which they act and new drug leads are discovered on the basis of target structure and function. Until the mid-1980s the information often flowed in reverse: investigators began with organic molecules and sought targets, relating receptors not by sequence or structure but by their ligands. Recently, investigators have returned to this chemical view of biology, bringing to it systematic and quantitative methods of relating targets by their ligands. This has allowed the discovery of new targets for established drugs, suggested the bases for their side effects, and predicted the molecular targets underlying phenotypic screens. The bases for these new methods, some of their successes and liabilities, and new opportunities for their use are described. So dominant has the molecular biology view of pharmacology become that it is difficult to remember that even 25 years ago it was little more than an aspiration. Today we understand the activity of drugs and reagents first through the specific, clonable receptor molecules with which they interact. To understan

Bone Marrow Cell Colonization Of, and Extracellular Matrix Expression On, Biodegradable Polymers

Poly(DL-lactide-co-glycolide)s (PLGAs) have been proposed as substrata for bone tissue engineering. In the experiments reported herein, we sought to identify the optimum lactide to glycolide ratio, from the series 85:15, 75:25, 50:50, or poly-(DL-lactide) (PLA), for the elaboration of bone matrix by cultured rat bone marrow cells (RBMC) on two-dimensional substrates. Having identified PLGA 75:25 as the optimum for bone matrix elaboration by RBMC, we produced three dimensional foams from this copolymer. For the two dimensional substrata, glass coverslips were spin-coated with one of the PLGAs, or PLA. Cultures were maintained for two weeks. We employed a new technique to label the elaborated bone matrix with the fluorescent antibiotic tetracycline. Bone matrix was present to a varying degree dependent on substrate composition: PLGA 75:25 = TCP \u3e PLGA 85:15 \u3e \u3e PLA. No bone matrix was observed on PLGA 50:50 or on uncoated glass coverslips. Cell proliferation was similar on each surface except PLA on which they did not proliferate. Cell morphology was assessed by scanning electron microscopy. Based on these results, three dimensional devices were produced from PLGA 75:25. Our results demonstrate that the copolymer ratios that maximize cell proliferation are not identical to the that optimize bone matrix elaboration. Furthermore, despite the intended use of three dimensional matrices for connective tissue engineering applications, bone marrow-derived cells produced only a superficial matrix layer that did not invade the scaffold, whether produced by either the salt leaching or freeze-drying procedures employed

Ligand Similarity Complements Sequence, Physical Interaction, and Co-Expression for Gene Function Prediction

The expansion of protein-ligand annotation databases has enabled large-scale networking of proteins by ligand similarity. These ligand-based protein networks, which implicitly predict the ability of neighboring proteins to bind related ligands, may complement biologically-oriented gene networks, which are used to predict functional or disease relevance. To quantify the degree to which such ligand-based protein associations might complement functional genomic associations, including sequence similarity, physical protein-protein interactions, co-expression, and disease gene annotations, we calculated a network based on the Similarity Ensemble Approach (SEA: sea.docking.org), where protein neighbors reflect the similarity of their ligands. We also measured the similarity with functional genomic networks over a common set of 1,131 genes, and found that the networks had only small overlaps, which were significant only due to the large scale of the data. Consistent with the view that the networks contain different information, combining them substantially improved Molecular Function prediction within GO (from AUROC~0.63-0.75 for the individual data modalities to AUROC~0.8 in the aggregate). We investigated the boost in guilt-by-association gene function prediction when the networks are combined and describe underlying properties that can be further exploited

Synthesis and adsorption of polymers :: control of polymer and surface structure/

Polymer surface modification can be accomplished by several techniques including chemical reaction and adsorption. In Chapter I, a simple and versatile technique to introduce carboxylic acid functionality to the surfaces of three fluoropolymer film samples is described. In Chapter II, the adsorption of neutral poly(scL-lysine) (PLL) from solution to the water-fluoropolymer interface is described. Chapter III combines the methods of surface modification described in Chapters I and II and discusses the adsorption of charged PLL to a carboxylic acid-functionalized fluoropolymer film surface. The hydrophobic interaction as a driving force for adsorption is further studied in Chapter IV where the synthesis and adsorption of poly(ethylene oxide) (PEO) and its derivatives are discussed. The syntheses of carboxylic acid-functionalized fluoropolymer films rely upon a two step mechanism where unsaturation, introduced in the first step, is oxidatively removed in the second step; one acidic group per twelve to sixteen repeat units was introduced to the surface. Contact angles (\theta\sb{\rm A}/\theta\sb{\rm R}) of the acid-functionalized fluoropolymer films decrease with increasing pH: PVF\sb2-CO\sb2H (77\sp\circ/39\sp\circ decreases to 68\sp\circ/25\sp\circ); PCTFE-CO\sb2H (93\sp\circ/55\sp\circ decreases to 93\sp\circ/43\sp\circ); and FEP-CO\sb2H (101\sp\circ/78\sp\circ decreases to 97\sp\circ/61\sp\circ). The adsorption of poly(scL-lysine) (PLL) to the water-FEP interface was controlled by pH of the aqueous solution and PLL solution conformation. Only neutral, $\alpha$-helical PLL adsorbed to FEP (FEP-PLL). The adsorption of PLL to carboxylic acid-functionalized FEP, FEP-CO\sb2H, was controlled by an electrostatic interaction; both a hydrogen bonding interaction between FEP-carboxylic acid and PLL backbone and an ionic interaction between FEP-carboxylate and PLL-ammonium enhanced adsorption. Both FEP-PLL (80\sp\circ/16\sp\circ) and FEP-CO\sb2H-PLL (78\sp\circ/29\sp\circ) are more hydrophilic than FEP. FEP-PLL-$\varepsilon$-amine reacts with 3,5-dinitrobenzoyl chloride in 65% yield whereas FEP-CO\sb2H-PLL-$\varepsilon$-amine reacts in 100% yield. Adsorption of PLL to FEP and FEP-CO\sb2H improves the peel strength of adhesive joints prepared with these substrates and the adhesion and growth of biological cells on these film samples. PEO (5,000 to 50,000 g/mole and polydispersity indices of 1.07 to 1.17) was synthesized by anionic ring opening polymerization of ethylene oxide in THF with triethylene glycol monomethyl ether potassium initiation. PEO was end-capped (PEO-R) by reaction with a (perfluoro)alkyl acid chloride in THF with pyridine catalysis. A polar interaction between substrate and segment controlled adsorption at the fluoropolymer-water interface; PEO adsorbed preferentially to PVF\sb2 over PCTFE and FEP. Both PEO and PEO-R adsorbed to the polystyrene latex-water interface; the latter formed a thicker adsorbed layer. PEO-R showed increased surface activity over PEO at the air-water interface; PEO-perfluorodecanoate decreased the surface tension of water to 35 dyn/cm