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Existence of piedmont zone in a river bed is a critical parameter from among numerous variations of topographical, geological and geographical conditions that can significantly influence the river flow scenario. Downstream flow situation assessed by routing of upstream hydrograph may yield higher flow depth if existence of such high infiltration zone is ignored and therefore it is a matter of concern for water resources planning and flood management. This work proposes a novel modified hydrodynamic model that has the potential to accurately determine the flow scenario in presence of piedmont zone. The model has been developed using unsteady free surface flow equations, coupled with Green-Ampt infiltration equation as governing equation. For solution of the governing equations Beam and Warming implicit finite difference scheme has been used. The proposed model was first validated from the field data of Trout Creek River showing excellent agreement. The validated model was then applied to a hypothetical river reach commensurate with the size of major tributaries of Brahmaputra Basin of India. Results indicated a 10% and 14% difference in the maximum value of discharge and depth hydrograph in presence and absence of piedmont zone respectively. Overall this model was successfully used to accurately predict the effect of piedmont zone on the unsteady flow in a river.

Förster resonance energy transfer (FRET) is a nonradiative process for the transfer of energy from an optically excited donor molecule (D) to an acceptor molecule (A) in the ground state. The underlying theory predicting the dependence of the FRET efficiency on the sixth power of the distance between D and A has stood the test of time. In contrast, a comprehensive kinetic-based theory developed recently for FRET efficiencies among multiple donors and acceptors in multimeric arrays has waited for further testing. That theory has been tested in the work described in this article using linked fluorescent proteins located in the cytoplasm and at the plasma membrane of living cells. The cytoplasmic constructs were fused combinations of Cerulean as donor (D), Venus as acceptor (A), and a photo-insensitive molecule (Amber) as a nonfluorescent (N) place holder: namely, NDAN, NDNA, and ADNN duplexes, and the fully fluorescent quadruplex ADAA. The membrane-bound constructs were fused combinations of GFP2 as donor (D) and eYFP as acceptor (A): namely, two fluorescent duplexes (i.e., DA and AD) and a fluorescent triplex (ADA). According to the theory, the FRET efficiency of a multiplex such as ADAA or ADA can be predicted from that of analogs containing a single acceptor (e.g., NDAN, NDNA, and ADNN, or DA and AD, respectively). Relatively small but statistically significant differences were observed between the measured and predicted FRET efficiencies of the two multiplexes. While elucidation of the cause of this mismatch could be a worthy endeavor, the discrepancy does not appear to question the theoretical underpinnings of a large family of FRET-based methods for determining the stoichiometry and quaternary structure of complexes of macromolecules in living cells., (Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

The literature on GPCR (G-protein-coupled receptor) homo-oligomerization encompasses conflicting views that range from interpretations that GPCRs must be monomeric, through comparatively newer proposals that they exist as dimers or higher-order oligomers, to suggestions that such quaternary structures are rather ephemeral or merely accidental and may serve no functional purpose. In the present study we use a novel method of FRET (Förster resonance energy transfer) spectrometry and controlled expression of energy donor-tagged species to show that M(3)Rs (muscarinic M(3) acetylcholine receptors) at the plasma membrane exist as stable dimeric complexes, a large fraction of which interact dynamically to form tetramers without the presence of trimers, pentamers, hexamers etc. That M(3)R dimeric units interact dynamically was also supported by co-immunoprecipitation of receptors synthesized at distinct times. On the basis of all these findings, we propose a conceptual framework that may reconcile the conflicting views on the quaternary structure of GPCRs.

Pseudomonas aeruginosa is a pathogenic Gram-negative bacterium that affects patients with cystic fibrosis and immunocompromised individuals. This bacterium coexpresses two unique forms of lipopolysaccharides (LPSs) on its surface, the A- and B-band LPS, which are among the main virulence factors that contribute to its pathogenicity. The polysaccharides in A-band LPSs are synthesized in the cytoplasm and translocated into the periplasm via an ATP-binding cassette (ABC) transporter consisting of a transmembrane protein, Wzm, and a cytoplasmic nucleotide-binding protein, Wzt. Most of the biochemical studies of A-band PSs in Pseudomonas aeruginosa are focused on the stages of the synthesis and ligation of PS, leaving the export stage involving the ABC transporter mostly unexplored. This difficulty is compounded by the fact that the subunit composition and structure of this bi-component ABC transporter are still unknown. Here we propose a simple but powerful method, based on Förster Resonance Energy Transfer (FRET) and optical micro-spectroscopy technology, to probe the structure of dynamic (as opposed to static) protein complexes in living cells. We use this method to determine the association stoichiometry and quaternary structure of the Wzm-Wzt complex in living cells. It is found that Wzt forms a rhombus-shaped homo-tetramer which becomes a square upon co-expression with Wzm, and that Wzm forms a square-shaped homo-tetramer both in the presence and absence of Wzt. Based on these results, we propose a structural model for the double-tetramer complex formed by the bi-component ABC transporter in living cells. An understanding of the structure and behavior of this ABC transporter will help develop antibiotics targeting the biosynthesis of the A-band LPS endotoxin.

Introduction: Aspirin has been used as an analgesic from time immemorial. But the recent advances on various aspects of it in reducing risk of various fatal and non fatal diseases warrant a re-look., Objective: This study has been undertaker to assess the anti inflammatory and analgesic action of aspirin and Nifedipine alone as well as in combination and their individual and synergistic effect as anti-inflammatory and analgesic drug., Materials and Methods: The anti - inflammatory and anti - nociceptive effect of aspirin and nifedipine was studied in a group of albino rats of Sprague Dowly strain. Anti - inflammatory action of the drugs were tested in experimentally produced inflammatory model by injecting turpentine oil in to the synovial cavity of knee joint of rats and anti - nociceptive effect was studied by hot plate method., Results: From the study it was observed that nifedipine alone was a better anti - inflammatory drug causing 40.10 percent reduction of experimentally produced inflammation in the studied rats on the 12th day of observation compared to aspirin alone (33.80 %) and aspirin - nifedipine combination (39.82%) but as an analgesic nifedipine alone (51.20%) was not found to be as effective as aspirin(88.96%) at 90 minutes of observation. However, when nifedipine was combined with aspirin, it potentiated the anti - nociceptive action of aspirin (107.64 %) at 90 minutes of observation which was statistically significant (P<0.01)., Conclusion: The above finding demonstrated that the dose of Non Steroidal Anti - inflammatory Drugs (NSAIDs) probably could be reduced when it is combined with Calcium Channel Blockers (CCBs) and thus the adverse effect of NSAIDs could be reduced considerably. Student's t test was applied for statistical analysis.

Pharmacogenomics deals with the genetic basis underlying variable drug response in individual patients. It encompasses sum of all genes. Numerous genes may play a role in drug response and toxicity. The newly emerging genomic technologies enable the search for relevant genes and their variants to include the entire genome and help in the search for candidate genes. Moreover pharmacogenomic analysis can identify the disease susceptibility genes representing potential new drug targets. The current concept of drug therapy is to apply treatment for a large population group whereas application of pharmacogenomic will help individual application of drug therapy or on smaller patient sub population but whether this individualized medicine will lead to improved and economically feasible therapy is yet to be seen. This is again complicated by various ethical and legal issues. In this article some of the issues are highlighted.