Encoding combinatorial libraries: A novel application of fluorescent silica colloids

A major challenge associated with using large chemical libraries synthesized on microscopic solid support beads is the rapid discrimination of individual compounds in these libraries. This challenge can be overcome by encoding the beads with 1 mum silica colloidal particles (reporters) that contain specific and identifiable combinations of fluorescent byes. The colored bar code generated on support beads during combinatorial library synthesis can be easily, rapidly, and inexpensively decoded through the use of fluorescence microscopy. All reporters are precoated with polyelectrolytes [poly(acrylic acid), PAA, poly(sodium 4-styrenesulfonate PSSS, polyethylenimine, PEI, and/or poly(diallyldimethylammonium chloride), PDADMAC] with the aim of enhancing surface charge, promoting electrostatic attraction to the bead, and facilitating polymer bridging between the bead and reporter for permanent adhesion. As shown in this article, reporters coated with polyelectrolytes clearly outperform uncoated reporters with regard to quantity of attached reporters per bead (54 +/- 23 in 2500 mum(2) area for PEI/PAA coated and 11 +/- 6 for uncoated reporters) and minimization of cross-contamination (1 red reporter in 2500 mum(2) area of green-labeled bead for PEI/PAA coated and 26 +/- 15 red reporters on green-labeled beads for uncoated reporters after 10 days). Examination of various polyelectrolyte systems shows that the magnitude of the xi -potential of polyelectrolyte-coated reporters (-64 mV for PDADMAC/PSSS and -42 mV for PEI/PAA-coated reporters) has no correlation with the number of reporters that adhere to the solid support beads (21 +/- 16 in 2500 mum(2) area for PDADMAC/PSSS and 54 +/- 23 for PEI/PAA-coated reporters). The contribution of polymer bridging to the adhesion has a far greater influence than electrostatic attraction and is demonstrated by modification of the polyelectrolyte multilayers using gamma irradiation of precoated reporters either in aqueous solution or in polyelectrolyte solution.

Structure development in octadecyl trimethylammonium templated silicate films grown at the air/water interface

The mechanism of growth of silicate films at the air/liquid interface has been investigated in situ by a series of grazing incidence diffraction experiments using a 20 x 25 cm(2) imaging plate as the detector. C(18)TAX (X = Br- or Cl-) has been used as the film templating surfactant. The formation of a layered phase, prior to growth of the hexagonal mesophase in C(18)TABr templated films. has been seen. This layered structure has a significantly shorter d spacing compared to the final hexagonal film (43 versus 48 Angstrom, respectively). The correlation lengths associated with the development of the hexagonal in-plane diffraction spots are much longer in-plane than perpendicular to the air/liquid interface (300 Angstrom versus 50 Angstrom). This implies that the film forms via the growth or aggregation of islands that are initially only a micelle or two thick. which then grow down into the solution.

Exploratory research: Citizen participation, local government and sustainable development in Australia

Exploratory research reported in this paper was undertaken in Adelaide, Australia during 1998/99. The purpose of the research is to explore local development practice as evidenced through the experiences and actions of local citizens, community based groups and local government (Neuman, 1994). Results from this first stage research suggest that sustainability initiatives in Australia might best be implemented through a collaborative approach at the local community level involving local citizens working in partnership with local government. Copyright (C) 2002 John Wiley & Sons, Ltd and ERP Environment.

An economic evaluation of plasma production via erythroplasmapheresis and whole blood collection

This paper presents cost-effectiveness analyses (CEAs) of plasma collection via two alternative methods: whole blood collection (WBC) and erythroplasmapheresis collection (EPC). The objective of the study is to provide an answer to the question 'What is the least-cost method of plasma production'. This question is answered, both from the viewpoint of the blood collection agency (using financial CEA) and from that of 'society' as a whole (using economic CEA). We employ detailed financial data and economic survey data for collections made by a blood collection agency and to WBC and EPC donors in Brisbane, Australia. The results indicate that, despite the superior yield provided by EPC, WBC is actually more cost-effective. This result is robust to thorough sensitivity analysis and arises regardless of whether an economic or financial perspective is taken. We conclude that, ceteris paribus, the cost of recruiting new plasma donors would need to be quite substantial for marginal investments in EPC to be considered cost-effective. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Developing a framework for assessment of the environmental determinants of walking and cycling

The focus for interventions and research on physical activity has moved away from vigorous activity to moderate-intensity activities, such as walking. In addition, a social ecological approach to physical activity research and practice is recommended. This approach considers the influence of the environment and policies on physical activity. Although there is limited empirical published evidence related to the features of the physical environment that influence physical activity, urban planning and transport agencies have developed policies and strategies that have the potential to influence whether people walk or cycle in their neighbourhood. This paper presents the development of a framework of the potential environmental influences on walking and cycling based on published evidence and policy literature, interviews with experts and a Delphi study. The framework includes four features: functional, safety, aesthetic and destination; as well as the hypothesised factors that contribute to each of these features of the environment. In addition, the Delphi experts determined the perceived relative importance of these factors. Based on these factors, a data collection tool will be developed and the frameworks will be tested through the collection of environmental information on neighbourhoods, where data on the walking and cycling patterns have been collected previously. Identifying the environmental factors that influence walking and cycling will allow the inclusion of a public health perspective as well as those of urban planning and transport in the design of built environments. (C) 2002 Elsevier Science Ltd., All rights reserved.

Structural development of silicated films self-assembled at the air-water interface

The development of structure perpendicular to and in the plane of the interface has been studied for mesoporous silicate films self-assembled at the air/water interface. The use of constrained X-ray and neutron specular reflectometry has enabled a detailed study of the structural development perpendicular to the interface during the pre-growth phase. Off-specular neutron reflectometry and grazing incidence X-ray diffraction has enabled the in-plane structure to be probed with excellent time resolution. The growth mechanism under the surfactant to silicate source ratios used in this work is clearly due to the self-assembly of micellar and molecular species at the air/liquid interface, resulting in the formation of a planar mesoporous film that is tens of microns thick. (C) 2003 Elsevier Science B.V. All rights reserved.

Development and subunit composition of synaptic NMDA receptors in the amygdala: NR2B Synapses in the adult central amygdala

NMDA receptors are well known to play an important role in synaptic development and plasticity. Functional NMDA receptors are heteromultimers thought to contain two NR1 subunits and two or three NR2 subunits. In central neurons, NMDA receptors at immature glutamatergic synapses contain NR2B subunits and are largely replaced by NR2A subunits with development. At mature synapses, NMDA receptors are thought to be multimers that contain either NR1/NR2A or NR1/NR2A/NR2B subunits, whereas receptors that contain only NR1/NR2B subunits are extrasynaptic. Here, we have studied the properties of NMDA receptors at glutamatergic synapses in the lateral and central amygdala. We find that NMDA receptor-mediated synaptic currents in the central amygdala in both immature and mature synapses have slow kinetics and are substantially blocked by the NR2B-selective antagonists (1S, 2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propano and ifenprodil, indicating that there is no developmental change in subunit composition. In contrast, at synapses on pyramidal neurons in the lateral amygdala, whereas NMDA EPSCs at immature synapses are slow and blocked by NR2B-selective antagonists, at mature synapses their kinetics are faster and markedly less sensitive to NR2B-selective antagonists, consistent with a change from NR2B to NR2A subunits. Using real-time PCR and Western blotting, we show that in adults the ratio of levels of NR2B to NR2A subunits is greater in the central amygdala than in the lateral amygdala. These results show that the subunit composition synaptic NMDA receptors in the lateral and central amygdala undergo distinct developmental changes.

Molecular diversity through sugar scaffolds

Monosaccharides provide an excellent platform to tailor molecular diversity by appending desired substituents at selected positions around the sugar scaffold. The presence of five functionalized and stereo-controlled centres on the sugar scaffolds gives the chemist plenty of scope to custom design molecules to a pharmacophore model. This review focuses on the peptidomimetic developments in this area, as well as the concept of tailoring structural and functional diversity in a library using carbohydrate scaffolds and how this can lead to increased hit rates and rapid identification of leads, which has promising prospects for drug development.

Development Resource Planning: Complexity of Product Development and the Capacity to Launch New Products

Overcommitment of development capacity or development resource deficiencies are important problems in new product development (NPD). Existing approaches to development resource planning have largely neglected the issue of resource magnitude required for NPD. This research aims to fill the void by developing a simple higher-level aggregate model based on an intuitive idea: The number of new product families that a firm can effectively undertake is bound by the complexity of its products or systems and the total amount of resources allocated to NPD. This study examines three manufacturing companies to verify the proposed model. The empirical results confirm the study`s initial hypothesis: The more complex the product family, the smaller the number of product families that are launched per unit of revenue. Several suggestions and implications for managing NPD resources are discussed, such as how this study`s model can establish an upper limit for the capacity to develop and launch new product families.

Petroleum royalties and regional development in Brazil: The economic growth of recipient towns

In 1997, Brazil approved law n(cr) 9478, establishing new rules for sharing petroleum royalties with Brazilian municipalities. The goal of this paper is to evaluate whether royalties distributed under the new law have contributed for the development of benefited municipalities. For that the difference-indifferences estimator (diff-in-diff) is used, which compares the evolution of the economic product into the municipality affected by the new law with the unaffected ones, by exploring the new legislation as an exogenous change. The data refer to the municipal gross domestic product (GDP) growth rate before and after the event. Results are surprising, showing that royalty receivers grew less than municipalities that did not receive such resources. The difference is small but statistically significant. In general, an increase of one real in royalties per capita reduces the growth rate of the municipal product in 0.002 percentile points. (C) 2009 Elsevier Ltd. All rights reserved.

Social Movements and the Dynamics of Rural Territorial Development in Latin America

This special section brings together 4 of the 12 studies conducted within a research program analyzing the relationships among social mobilization, governance. and rural development in contemporary Latin America. The introduction Lives an overview of the contemporary significance of social movements For rural development dynamics in the region, and of the principal insights of the section papers and the broader research program of which they were a part. This significance varies Lis an effect of two distinct and uneven geographics: the geography of social movements themselves and the geography of the rural political economy. The effects that movements have oil the political economy of rural development also depend significantly oil internal characteristics of these movements. The paper identifies several such characteristics. The general pattern is that movements have had far more effect oil widening the political inclusiveness of rural development than they have oil improving its economic inclusiveness and dynamism. (c) 2008 Elsevier Ltd. All rights reserved.

Social Movements Beyond the Iron Cage: Weak Ties in Territorial Development

The incentives and governance system of organizations are important in explaining how they behave in localized development processes. This article builds on the observation that the literature on territorial development does not generally address the action of social movements. At the same time, research on social movements rarely studies their effects on the territories ill which they act. This text is a contribution to fill this gap. It compares two social movement organizations: a trade union federation and a credit cooperative system operating throughout southern Brazil, Both organizations share common origins and social bases, yet their impacts oil territories have been quite different. The analysis focuses Oil the social ties that link trade unions and cooperatives to their territories to show that governance systems may explain the performance of each organization, especially with regard to their capacity for innovation. (c) 2008 Elsevier Ltd. All rights reserved.