Sirtuins: Multifaceted Drug Targets

Sirtuin (Sir2) proteins being key regulators of numerous cellular processes have been, over the recent past, the subject of intense study. Sirs have been implicated in diverse physiological processes ranging from aging and cancer to neurological dysfunctions. Studies on Sir2s using tools of genetics, molecular biology, biochemistry and structural biology have provided significant insight into the diverse functions of this class of deacetylases. This apart, medicinal chemistry approaches have enabled the discovery of modulators (both activators and inhibitors) of Sir2 activity of diverse chemical structures and properties. The availability of these small molecule modulators of Sir2 activity not only has pharmacological significance but also opens up the possibility of exploiting chemical genetic approaches in understanding the role of this multi-functional enzyme in cellular processes.

Biologically triggered exploding protein based microcapsules for drug delivery

Biologically triggered exploding microcapsules were synthesized by layer-by-layer assembly of biopolymers. The microcapsules showed controlled rupturing behaviour upon exposure to a pathologically relevant biomolecule, trypsin. These microcapsules offer significant potential for clinical applications.

Investigation of biodegradable and biocompatible castor oil poly(mannitol-citric-sebacate) polyester as a drug carrier

Castor oil-based poly(mannitol-citric sebacate) was synthesized by simple, catalyst-free melt condensation process using monomers having potential to be metabolized in vivo. The polymer was characterized using various techniques and the tensile and hydration properties of the polymers were also determined. The biocompatibility of the polymer was tested using human foreskin fibroblasts cells. The in vitro degradation studies show that the time for complete degradation of the polymer was more than 21 days. The usage of castor oil polyester as a drug carrier was analysed by doping the polymer with 5-fluorouracil model drug and the release rate was studied by varying the percentage loading of drugs and the pH of the PBS solution medium. The cumulative drug-release profiles exhibited a biphasic release with an initial burst release and cumulative 100% release within 42 h. To understand the role of the polymer as a drug carrier in the release behaviour, drug-release studies were conducted with another drug, isoniazid. The release behaviour of isoniazid drug from the same polymer matrix followed an nth order kinetic model and 100% cumulative release was achieved after 12 days. The variation in the release behaviour for two model drugs from the same polymer matrix suggests a strong interaction between the polymer and the drug molecule.

Tensile force distribution along the reinforcement for reinforced soil foundations

In a reinforced soil bed system reinforcement layer is usually placed with or without end anchorage. Since soil is weak in tension reinforcement develop tension under the applied load or the displacement of the footing. This tensile force is distributed along the length of the reinforcement subjected to the end condition. The reinforccement tension helps in distributing the load over a wider area, and becomes more effective at large induced settlements. As a result, vertical componenent of tensile force generated becomes effective in reducing applied load. However, very few studies to quantify the tensile force along the reinforcement have been reported in the literature. In this paper an attempt has been made to obtain the true nature of tensile force distribution along the reinforcement. For a reinforced soil bed below a strip footing this paper brings out induced tensile force distribution along the reinforcement at different load levels and for different types of reinforcements.

Chain Length Effects on Helix-Hairpin Distribution in Short Peptides with Aib-(D)Ala and Aib-Aib Segments

The Aib-(D)Ala dipeptide segment has a tendency to form both type-I'/III' and type-I/III beta-turns. The occurrence of prime turns facilitates the formation of beta-hairpin conformations, while type-I/III turns can nucleate helix formation. The octapeptide Boc-Leu-Phe-Val-Aib-(D)Ala-Leu-Phe-Val-OMe (1) has been previously shown to form a beta-hairpin in the crystalline state and in solution. The effects of sequence truncation have been examined using the model peptides Boc-Phe-Val-Aib-Xxx-Leu-Phe-NHMe (2, 6), Boc-Val-Aib-Xxx-Leu-NHMe (3, 7), and Boc-Aib-Xxx-NHMe (4, 8), where Xxx = (D)Ala, Aib. For peptides with central Aib-Aib segments, Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe (6), Boc-Val-Aib-Aib-Leu-NHMe (7), and Boc-Aib-Aib-NHMe (8) helical conformations have been established by NMR studies in both hydrogen bonding (CD(3)OH) and non-hydrogen bonding (CDCl(3)) solvents. In contrast, the corresponding hexapeptide Boc-Phe-Val-Aib-(D)Ala-Leu-Phe-Val-NHMe (2) favors helical conformations in CDCl(3) and beta-hairpin conformations in CD(3)OH. The beta-turn conformations (type-I'/III) stabilized by intramolecular 4 -> 1 hydrogen bonds are observed for the peptide Boc-Aib-(D)Ala-NHMe (4) and Boc-Aib-Aib-NIiMe (8) in crystals. The tetrapeptide Boc-Val-Aib-Aib-Leu-NHMe (7) adopts an incipient 3(10)-helical conformation stabilized by three 4 -> 1 hydrogen bonds. The peptide Boc-Val-Aib-(D)Ala-Leu-NHMe (3) adopts a novel et-turn conformation, stabilized by three intramolecular hydrogen bonds (two 4 -> 1 and one 5 -> 1). The Aib-L(D)Ala segment adopts a type-I' beta-turn conformation. The observation of an NOE between Val (1) NH <-> HNCH(3) (5) in CD(3)OH suggests, that the solid state conformation is maintained in methanol solutions. (C) 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 744-756, 2011.

Mass Distribution Studies in Effervescent Sprays

An experimental study on liquid mass distribution in effervescent sprays using water and air as working fluids is presented in this paper. Optical patternation and techniques of image processing are employed for analyzing the spray. The flow regime inside the effervescent atomizer largely dictates the mass distribution patterns. The patterns are seen to vary from concentrated, poorly atomized liquid lumps to uniformly distributed, fine droplets as the flow regime changes from bubbly flow to annular flow. A large variety of instantaneous spray patterns are observed in bubbly flow regime indicating a highly unsteady atomization process. However, relatively better consistency in spray patterns is observed at higher gas flow rates. Thus, the degree of unsteadiness gradually diminishes as gas flow rate is increased. The axial evolution of the spray in annular mode shows good mixing of liquid and gas across the interface.

A robust three phase power flow algorithm for radial distribution systems

An efficient load flow solution technique is required as a part of the distribution automation (DA) system for taking various control and operations decisions. This paper presents an efficient and robust three phase power flow algorithm for application to radial distribution networks. This method exploits the radial nature of the network and uses forward and backward propagation to calculate branch currents and node voltages. The proposed method has been tested to analyse several practical distribution networks of various voltage levels and also having high R/X ratio. The results for a practical distribution feeder are presented for illustration purposes. The application of the proposed method is also extended to find optimum location for reactive power compensation and network reconfiguration for planning and day-to-day operation of distribution networks.

A Robust Three Phase State Estimation for Distribution Networks

Electric power utilities are installing distribution automation systems (DAS) for better management and control of the distribution networks during the recent past. The success of DAS, largely depends on the availability of reliable database of the control centre and thus requires an efficient state estimation (SE) solution technique. This paper presents an efficient and robust three-phase SE algorithm for application to radial distribution networks. This method exploits the radial nature of the network and uses forward and backward propagation scheme to estimate the line flows, node voltage and loads at each node, based on the measured quantities. The SE cannot be executed without adequate number of measurements. The extension of the method to the network observability analysis and bad data detection is also discussed. The proposed method has been tested to analyze several practical distribution networks of various voltage levels and also having high R:X ratio of lines. The results for a typical network are presented for illustration purposes. © 2000 Elsevier Science S.A. All rights reserved.