Lipid, sugar and liposaccharide based delivery systems

Although there are formidable barriers to the oral delivery of biologically active drugs, considerable progress in the field has been made, using both physical and chemical strategies of absorption enhancement. A possible method to enhance oral absorption is to exploit the phenomenon of lipophilic modification and mono and oligosaccharide conjugation. Depending on the uptake mechanism targeted, different modifications can be employed. To target passive diffusion, lipid modification has been used, whereas the targeting of sugar transport systems has been achieved through drugs conjugated with sugars. These drug delivery units can be specifically tailored to transport a wide variety of poorly absorbed drugs through the skin, and across the barriers that normally inhibit absorption from the gut or into the brain. The delivery system can be conjugated to the drug in such a way as to release the active compound after it has been absorbed (i.e. the drug becomes a prodrug), or to form a biologically stable and active molecule (i.e. the conjugate becomes a new drug moiety). Examples where lipid, sugar and lipid-sugar conjugates have resulted in enhanced drug delivery will be highlighted in this review.

Lipid, sugar and liposaccharide based delivery systems 2

The vast majority of biologically active compounds will never be considered as potential drugs due to inherently poor bioavailability. This review discusses the progress in the development of chemical systems to improve the metabolic stability, absorption and physicochemical properties of potential drugs. Delivery systems that involve the conjugation of lipid and/or sugar moieties are highlighted, as well as novel methods of conjugation of these groups to drugs. The use of sugar molecules to target drugs to particular organs or cells is also discussed, as is the use of lipids in the growing area of gene delivery. This is an update of a previous review [1].

UML approach to the generation of test sequences for Java-based concurrent systems

Starting with a UML specification that captures the underlying functionality of some given Java-based concurrent system, we describe a systematic way to construct, from this specification, test sequences for validating an implementation of the system. The approach is to first extend the specification to create UML state machines that directly address those aspects of the system we wish to test. To be specific, the extended UML state machines can capture state information about the number of waiting threads or the number of threads blocked on a given object. Using the SAL model checker we can generate from the extended UML state machines sequences that cover all the various possibilities of events and states. These sequences can then be directly transformed into test sequences suitable for input into a testing tool such as ConAn. As an illustration, the methodology is applied to generate sequences for testing a Java implementation of the producer-consumer system. © 2005 IEEE

Methods for conflict resolution in policy-based management systems

While developments in distributed object computing environments, such as the Common Object Request Broker Architecture (CORBA) [17] and the Telecommunication Intelligent Network Architecture (TINA) [16], have enabled interoperability between domains in large open distributed systems, managing the resources within such systems has become an increasingly complex task. This challenge has been considered for several years within the distributed systems management research community and policy-based management has recently emerged as a promising solution. Large evolving enterprises present a significant challenge for policy-based management partly due to the requirement to support both mutual transparency and individual autonomy between domains [2], but also because the fluidity and complexity of interactions occurring within such environments requires an ability to cope with the coexistence of multiple, potentially inconsistent policies. This paper discusses the need of providing both dynamic (run-time) and static (compile-time) conflict detection and resolution for policies in such systems and builds on our earlier conflict detection work [7, 8] to introduce the methods for conflict resolution in large open distributed systems.

Investigation of electrical conductivity as a function of dopant-ion radius in the systems Zr0.75Ce0.08M0.17O1.92 (M=Nd, Sm, Gd, Dy, Ho, Y, Er, Yb, Sc)

Electrical conductivity versus dopant ionic radius studies in zirconia- and ceria-based, solid oxide fuel cell (SOFC) electrolyte systems have shown that oxygen-ion conductivity is highest when the host and dopant ions are similar in size [J. Am. Ceram. Soc. 48 (1965) 286; Solid State Ionics 37 (1989) 67; Solid State Ionics 5 (1981) 547]. Under these conditions, it is thought that the conduction paths within the crystal lattice become less distorted [Solid State Ionics 8 (1983) 201]. In this study, binary ZrO2-M2O3 unit cells were expanded, via the partial substitution of Ce+4 for Zr+4 into the lattice, in an attempt to identify new, ternary, zirconia/ceria-based electrolyte systems with enhanced electrical conductivity. The compositions Zr0.75Ce0.08M0.17O1.92 (M = Nd, Sm, Gd, Dy, Ho, Y, Yb, Sc) were prepared using traditional solid state techniques. Bulk phase characterisation and precise lattice parameter measurements were performed with X-ray diffraction techniques. Four-probe DC conductivity measurements between 400 and 900 degreesC showed that the dopant-ion radius influenced electrical conductivity. The conductivity versus dopant-ion radius trends previously observed in zirconia-based, binary systems are clearly apparent in the ternary systems investigated in this study. The addition of ceria was found to have a negative influence on the electrical conductivity over the temperature range 400-900 degreesC. It is suggested that distortion of the oxygen-ion conduction path by the presence of the larger M+3 and Ce+4 species (relative to Zr+4) is the reason for the decreasing electrical conductivity as a function of increasing dopant size and ceria addition, respectively. (C) 2002 Elsevier Science B.V. All rights reserved.

A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABA(A) receptor chloride channels

There is a significant clinical need to identify novel ligands with high selectivity and potency for GABA(A), GABA(C) and glycine receptor Cl- channels. Two recently developed, yellow fluorescent protein variants (YFP-I152L and YFP-V163S) are highly sensitive to quench by small anions and are thus suited to reporting anionic influx into cells. The aim of this study was to establish the optimal conditions for using these constructs for high-throughput screening of GABA(A), GABA(C) and glycine receptors transiently expressed in HEK293 cells. We found that a 70% fluorescence reduction was achieved by quenching YFP-I152L with a 10 s influx of I- ions, driven by an extemal I- concentration of at least 50 mM. The fluorescence quench was rapid, with a mean time constant of 3 s. These responses were similar for all anion receptor types studied. We also show the assay is sufficiently sensitive to measure agonist and antagonist concentration-responses using either imaging- or photomultiplier-based detection systems. The robustness, sensitivity and low cost of this assay render it suited for high-throughput screening of transiently expressed anionic ligand-gated channels. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Lipid based particulate formulations for the delivery of antigen

Particulate adjuvant systems are largely classified according to their functional characteristics, such as the nature of the typical immune response they induce, or their perceived mode of action. From a formulation science perspective, it is practical to classify antigen delivery systems according to the physical nature of the formulations. This article discusses lipid based particulate systems, grouped according to the nature of their predominant lipid constituent.

Development of a web-service-agents-based family wealth management system

The roiling financial markets, constantly changing tax law and increasing complexity of planning transaction increase the demand of aggregated family wealth management (FWM) services. However, current trend of developing such advisory systems is mainly focusing on financial or investment side. In addition, these existing systems lack of flexibility and are hard to be integrated with other organizational information systems, such as CRM systems. In this paper, a novel architecture of Web-service-agents-based FWM systems has been proposed. Multiple intelligent agents are wrapped as Web services and can communicate with each other via Web service protocols. On the one hand, these agents can collaborate with each other and provide comprehensive FWM advices. On the other hand, each service can work independently to achieve its own tasks. A prototype system for supporting financial advice is also presented to demonstrate the advances of the proposed Webservice- agents-based FWM system architecture.