Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site

Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present

Electroactive apparatus and methods

High performance electromechanical devices suitable for a wide range of applications are described. The electroactive devices are capable of operating in a manner that offers enhanced mechanical displacement responses and increased load-bearing capabilities. In one embodiment, the device is capable of providing a significantly increased level of free displacement. The electroactive devices include an electroactive composite which includes at least one electroactive material that may comprise an electrostrictive or a piezoelectric material and a tensioning device which is adapted for inducing a mechanical pre-load to the electroactive composite structure. The tensioning device exerts a mechanical pre-load upon the electroactive material which alters stress profile, increases mechanical energy and increases stored elastic energy of the electroactive devices

Improving access to medicines for non-communicable diseases in rural India: a mixed methods study protocol using quasi-experimental design

Exit interview tool. Exit interview tool used in baseline survey of the ATM study. (PDF 150 kb

Detection and Operation of Unintentional Islands in the Presence of Distributed Generation Units

The complexities and challenges for reliable operation of power system have increased due to various types of Distributed Generators (DG) in the Distribution Network (DN) to supply the increasing load demand. It necessitates a comprehensive approach in planning the system towards effective and reliable operation of the system. During the operation of the system, detection of unintentional islanding is critical as non-detection of islanding event could lead to cascaded failure of the system due to active or reactive power imbalance leading to frequency, angle or voltage instability. If undetected, the instability in the islanded part can cascade into the stable part of the system resulting in complete failure of the system. A robust Modified Islanding Detection Technique (MIDT) has been proposed for identifying the islanding event early and accurately in the distribution networks with DGs installed for multiple objectives and is compared with existing passive Islanding Detection Techniques (IDT). A rank-based load shedding scheme is proposed for stable and reliable operation of the identified island, which sheds only the most vulnerable loads in the island for regaining the frequency and voltage stabilities. The proposed MIDT and rank based load shedding schemes were tested on 11kV IEEE 118 Bus Test system

The repertoire of G protein-coupled receptors in the sea squirt Ciona intestinalis

<p>Abstract</p> <p>Background</p> <p>G protein-coupled receptors (GPCRs) constitute a large family of integral transmembrane receptor proteins that play a central role in signal transduction in eukaryotes. The genome of the protochordate <it>Ciona intestinalis </it>has a compact size with an ancestral complement of many diversified gene families of vertebrates and is a good model system for studying protochordate to vertebrate diversification. An analysis of the <it>Ciona </it>repertoire of GPCRs from a comparative genomic perspective provides insight into the evolutionary origins of the GPCR signalling system in vertebrates.</p> <p>Results</p> <p>We have identified 169 gene products in the <it>Ciona </it>genome that code for putative GPCRs. Phylogenetic analyses reveal that <it>Ciona </it>GPCRs have homologous representatives from the five major GRAFS (<it>Glutamate, Rhodopsin, Adhesion, Frizzled </it>and <it>Secretin</it>) families concomitant with other vertebrate GPCR repertoires. Nearly 39% of <it>Ciona </it>GPCRs have unambiguous orthologs of vertebrate GPCR families, as defined for the human, mouse, puffer fish and chicken genomes. The <it>Rhodopsin </it>family accounts for ~68% of the <it>Ciona </it>GPCR repertoire wherein the LGR-like subfamily exhibits a lineage specific gene expansion of a group of receptors that possess a novel domain organisation hitherto unobserved in metazoan genomes.</p> <p>Conclusion</p> <p>Comparison of GPCRs in <it>Ciona </it>to that in human reveals a high level of orthology of a protochordate repertoire with that of vertebrate GPCRs. Our studies suggest that the ascidians contain the basic ancestral complement of vertebrate GPCR genes. This is evident at the subfamily level comparisons since <it>Ciona </it>GPCR sequences are significantly analogous to vertebrate GPCR subfamilies even while exhibiting <it>Ciona </it>specific genes. Our analysis provides a framework to perform future experimental and comparative studies to understand the roles of the ancestral chordate versions of GPCRs that predated the divergence of the urochordates and the vertebrates.</p