On the mechanism of plastic flow at 86°k in quenched and aged aluminum

The plastic flow of quenched aluminium at 86°K was investigated by ‘differential-stress’ creep tests in order to evaluate the rate-controlling mechanism in as-quenched and fully aged states. The experimental values of activation volume (4·3 × 10−21 cm3 for as-quenched and 5·5×l0−21cm3 for fully aged) and the total energy for thermal activation process (0·4 ev for both) are in accordance with the jog hardening and loop hardening mechanisms in quenched and fully aged states respectively.

Retention Time Variability as a Mechanism for Animal Mediated Long-Distance Dispersal

Long-distance dispersal (LDD) events, although rare for most plant species, can strongly influence population and community dynamics. Animals function as a key biotic vector of seeds and thus, a mechanistic and quantitative understanding of how individual animal behaviors scale to dispersal patterns at different spatial scales is a question of critical importance from both basic and applied perspectives. Using a diffusion-theory based analytical approach for a wide range of animal movement and seed transportation patterns, we show that the scale (a measure of local dispersal) of the seed dispersal kernel increases with the organisms' rate of movement and mean seed retention time. We reveal that variations in seed retention time is a key determinant of various measures of LDD such as kurtosis (or shape) of the kernel, thinkness of tails and the absolute number of seeds falling beyond a threshold distance. Using empirical data sets of frugivores, we illustrate the importance of variability in retention times for predicting the key disperser species that influence LDD. Our study makes testable predictions linking animal movement behaviors and gut retention times to dispersal patterns and, more generally, highlights the potential importance of animal behavioral variability for the LDD of seeds.

Mechanism design problems in carbon economics

Reduction of carbon emissions is of paramount importance in the context of global warming and climate change. Countries and global companies are now engaged in understanding systematic ways of solving carbon economics problems, aimed ultimately at achieving well defined emission targets. This paper proposes mechanism design as an approach to solving carbon economics problems. The paper first introduces carbon economics issues in the world today and next focuses on carbon economics problems facing global industries. The paper identifies four problems faced by global industries: carbon credit allocation (CCA), carbon credit buying (CCB), carbon credit selling (CCS), and carbon credit exchange (CCE). It is argued that these problems are best addressed as mechanism design problems. The discipline of mechanism design is founded on game theory and is concerned with settings where a social planner faces the problem of aggregating the announced preferences of multiple agents into a collective decision, when the actual preferences are not known publicly. The paper provides an overview of mechanism design and presents the challenges involved in designing mechanisms with desirable properties. To illustrate the application of mechanism design in carbon economics,the paper describes in detail one specific problem, the carbon credit allocation problem.

Advances in the Mathematical Modelling of Hepatitis C Virus Dynamics

Mathematical models have provided key insights into the pathogenesis of hepatitis C virus (HCV) in vivo, suggested predominant mechanism(s) of drug action, explained confounding patterns of viral load changes in HCV infected patients undergoing therapy, and presented a framework for therapy optimization. In this article, I present an overview of the major advances in the mathematical modeling of HCV dynamics.

ZnO/Ag nanohybrid: synthesis, characterization, synergistic antibacterial activity and its mechanism

A highly homogeneous ZnO/Ag nanohybrid has been synthesized by a novel route, employing chitosan as mediator by purely electrostatic interaction. By employing various techniques such as powder XRD, UV-visible, IR spectroscopy and electron (SEM, TEM) microscopy, the formation of the nanohybrid has been established. The synergistic antibacterial effect of ZnO/Ag nanohybrid on Gram-positive and Gram-negative bacteria is found to be more effective, compared to the individual components (ZnO and Ag). Cytotoxicity experiments are carried out and the results are correlated to the solubility of the nanohybrid. A possible mechanism has been proposed for the antibacterial activity of ZnO/Ag nanohybrid, based on TEM studies on bacteria, carried out by employing the microtome technique and by EPR measurements on the hybrid.

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.

Growth mechanism of the Nb(X)Si-2 and [Nb(X)](5)Si-3 phases by reactive diffusion in Nb (X = Ti, Mo, or Zr)-Si systems

The effects of Mo, Ti, and Zr on the diffusion and growth of the Nb(X)Si-2 and Nb(X)(5)Si-3 phases in an Nb(X)-Si system are analyzed. The integrated diffusion coefficients are determined from diffusion couple experiments and compared with the data previously calculated in a binary Nb-Si system. The growth rates of both phases are affected by the addition of Mo and Zr, whereas the addition of Ti has no effect. The atomic mechanism of diffusion is also discussed based on the crystal structure and the possible changes in the defect concentrations due to alloying. Finally, the growth mechanism of the phases is discussed on the basis of a physico-chemical approach. (C) 2011 Elsevier Ltd. All rights reserved.

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.

Barrier crossing by a flexible long chain molecule - The kink mechanism

The problem and related earlier work All the above problems involve the passage of a long chain molecule, through a region in space, where the free energy per segment is higher, thus effectively presenting a barrier for the motion of the molecule. This is what we refer to as the Kramers proble...

The Role of Tool Design in Influencing the Mechanism for the Formation of Friction Stir Welds in Aluminum Alloy 7020

Design of the required tool is a key and important parameter in the technique of friction stir welding (FSW). This is so because tool design does exert a close control over the quality of the weld. In an attempt to optimize tool design and its selection, it is essential and desirable to understand the mechanisms governing the formation of the weld. In this research study, few experiments were conducted to systematically analyze the intrinsic mechanisms governing the formation of the weld and to effectively utilize the analysis to establish a logical basis for design of the tool. For this purpose, the experiments were conducted using different geometries of the shoulder and pin of the rotating tool in such a way that only tool geometry had an intrinsic influence on formation of the weld. The results revealed that for a particular diameter of the pin there is an optimum diameter of the shoulder. Below this optimum shoulder diameter, the weld does not form while above the optimum diameter the overall symmetry of the weld is lost. Based on experimental results, a mechanism for the formation of friction stir weld is proposed. A synergism of the experimental results with the proposed mechanism is helpful in establishing the set of welding parameters for a given material.

PAMAM Dendrimer-Drug Interactions: Effect of pH on the Binding and Release Pattern

Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. Using atomistic molecular dynamics (MD) simulations, we have analyzed the release pattern of four ligands (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine (PAMAM) dendrimer using the docking method. We have computed the potential of mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with drug molecules using umbrella sampling. From our calculated PMF values, we observe that soluble drugs (Sal and Ala) have lower energy barriers than insoluble drugs (Pbz and Prim). The order of ease of release pattern for these drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz. In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe much nonpolar contribution, and thus, their larger energy barriers can be reasoned to van der Waals contribution. From the hydrogen bonding analysis of the four PAMAM drug complexes under study, we found intermolecular hydrogen bonding to show less significant contribution to the free energy barrier. Another interesting feature appears while calculating the PMF profile of G5NP (nonprotonated)-PAMAM Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was found to be less when the drug is bound to nonprotonated dendrimer compared to the protonated dendrimer. Our results suggest that encapsulation of the drug molecule into the host PAMAM dendrimer should be carried out at higher pH values (near pH 10). When such complex enters the human body, the pH is around 7.4 and at that physiological pH, the dendrimer holds the drug tightly. Hence the release of drug can occur at a controlled rate into the bloodstream. Thus, our findings provide a microscopic picture of the encapsulation and controlled release of drugs in the case of dendrimer-based host-guest systems.

Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A Piggyback' Approach for Antimalarial Drug Discovery

Quest for new drug targets in Plasmodium sp. has underscored malonyl CoA:ACP transacylase (PfFabD) of fatty acid biosynthetic pathway in apicoplast. In this study, a piggyback approach was employed for the receptor deorphanization using inhibitors of bacterial FabD enzymes. Due to the lack of crystal structure, theoretical model was constructed using the structural details of homologous enzymes. Sequence and structure analysis has localized the presence of two conserved pentapeptide motifs: GQGXG and GXSXG and five key invariant residues viz., Gln109, Ser193, Arg218, His305 and Gln354 characteristic of FabD enzyme. Active site mapping of PfFabD using substrate molecules has disclosed the spatial arrangement of key residues in the cavity. As structurally similar molecules exhibit similar biological activities, signature pharmacophore fingerprints of FabD antagonists were generated using 0D-3D descriptors for molecular similarity-based cluster analysis and to correlate with their binding profiles. It was observed that antagonists showing good geometrical fitness score were grouped in cluster-1, whereas those exhibiting high binding affinities in cluster-2. This study proves important to shed light on the active site environment to reveal the hotspot for binding with higher affinity and to narrow down the virtual screening process by searching for close neighbors of the active compounds.

Mechanism of Fragility at BCL2 Gene Minor Breakpoint Cluster Region during t(14;18) Chromosomal Translocation

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear. Here, for the first time, we show that RAGs can nick mcr; however, the mechanism is unique. Three independent nicks of equal efficiency are generated, when both Mg2+ and Mn2+ are present, unlike a single nick during V(D)J recombination. Further, we demonstrate that RAG binding and nicking at the mcr are independent of nonamer, whereas a CCACCTCT motif plays a critical role in its fragility, as shown by sequential mutagenesis. More importantly, we recapitulate the BCL2 mcr translocation and find that mcr can undergo synapsis with a standard recombination signal sequence within the cells, in a RAG-dependent manner. Further, mutation to the CCACCTCT motif abolishes recombination within the cells, indicating its vital role. Hence, our data suggest a novel, physiologically relevant, nonamer-independent mechanism of RAG nicking at mcr, which may be important for generation of chromosomal translocations in humans.