Unifying Distributed Processing and Open Hypertext through a Heterogeneous Communication Model

A successful distributed open hypermedia system can be characterised by a scaleable architecture which is inherently distributed. While the architects of distributed hypermedia systems have addressed the issues of providing and retrieving distributed resources, they have often neglected to design systems with the inherent capability to exploit the distributed processing of this information. The research presented in this paper describes the construction and use of an open hypermedia system concerned equally with both of these facets

An Open Framework for Integrating Widely Distributed Hypermedia Resources

The success of the WWW has served as an illustration of how hypermedia functionality can enhance access to large amounts of distributed information. However, the WWW and many other distributed hypermedia systems offer very simple forms of hypermedia functionality which are not easily applied to existing applications and data formats, and cannot easily incorporate alternative functions which would aid hypermedia navigation to and from existing documents that have not been developed with hypermedia access in mind. This paper describes the extension to a distributed environment of the open hypermedia functionality of the Microcosm system, which is designed to support the provision of hypermedia access to a wide range of source material and application, and to offer straightforward extension of the system to incorporate new forms of information access

MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes

SummaryThere has been exponential growth in the number of membrane protein structures determined. Nevertheless, these structures are usually resolved in the absence of their lipid environment. Coarse-grained molecular dynamics (CGMD) simulations enable insertion of membrane proteins into explicit models of lipid bilayers. We have automated the CGMD methodology, enabling membrane protein structures to be identified upon their release into the PDB and embedded into a membrane. The simulations are analyzed for protein-lipid interactions, identifying lipid binding sites, and revealing local bilayer deformations plus molecular access pathways within the membrane. The coarse-grained models of membrane protein/bilayer complexes are transformed to atomistic resolution for further analysis and simulation. Using this automated simulation pipeline, we have analyzed a number of recently determined membrane protein structures to predict their locations within a membrane, their lipid/protein interactions, and the functional implications of an enhanced understanding of the local membrane environment of each protein

Accountability, Strategy, and International Non-Governmental Organizations

Increased prominence and greater influence expose international non-governmental development and environmental organizations (INGOs) to increased demands for accountability from a wide variety of stakeholdersdonors, beneficiaries, staffs, and partners among others. This paper focuses on developing the concept of INGO accountability, first as an abstract concept and then as a strategic idea with very different implications for different INGO strategies. We examine those implications for INGOs that emphasize service delivery, capacity-building, and policy influence. We propose that INGOs committed to service delivery may owe more accountability to donors and service regulators; capacity-building INGOs may be particularly obligated to clients whose capacities are being enhanced; and policy influence INGOs may be especially accountable to political constituencies and to influence targets. INGOs that are expanding their activities to include new initiatives may need to reorganize their accountability systems to implement their strategies effectively. This publication is Hauser Center Working Paper No. 7. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Predicting binding affinities for GPCR ligands using free-energy perturbation

Medicinal ChemistryDrug Delivery Technolog

The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations

Integrins are heterodimeric (αβ) cell surface receptors that are potential therapeutic targets for a number of diseases. Despite the existence of structural data for all parts of integrins, the structure of the complete integrin receptor is still not available. We have used available structural data to construct a model of the complete integrin receptor in complex with talin F2–F3 domain. It has been shown that the interactions of integrins with their lipid environment are crucial for their function but details of the integrin/lipid interactions remain elusive. In this study an integrin/talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin/talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2–F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes

Is the pen mightier than the sword? Exploring urban and rural health in Victorian England and Wales using the Registrar General Reports

YesIn AD 1836, the General Register Office (GRO) was established to oversee the national system of civil registration in England and Wales, recording all births, deaths and marriages. Additional data regarding population size, division size and patterns of occupation within each division permit urban and rural areas (and those with both urban and rural characteristics, described here as ‘mixed’) to be directly compared to each other. The annual Reports of the Registrar General summarize the collected data, including cause of and age at death, which is of particular value to historical demographers and bioarcheologists, allowing us to investigate demographic patterns in urban and rural districts in the nineteenth century. Overall, this paper aims to highlight how this documentary evidence can supplement osteological and paleopathological data to investigate how urbanization affected the health of past populations. It examines the data contained within the first Registrar General report (for 1837-8), in order to assess patterns of mortality of diverse rural, urban, and mixed populations within England and Wales at a point in time during a period of rapid urbanization. It shows that urban and mixed districts typically had lower life expectancy and different patterns in cause of death compared to rural areas. The paper briefly compares how the documentary data differs from information regarding health from skeletal populations, focusing on the city of London, highlighting that certain age groups (the very young and very old) are typically underrepresented in archeological assemblages and reminding us that, while the paleopathological record offers much in terms of chronic health, evidence of acute disease and importantly cause of death can rarely be ascertained from skeletal remains.This research was funded by the Royal Society of London (Grant Reference IES\R1\180138) and supported by the University of Bradford and SUNY Plattsburgh