Shear band spacing in gradient-dependent thermoviscoplastic materials

We study thermomechanical deformations of a viscoplastic body deformed in simple shear. The strain gradients are taken as independent kinematic variables and the corresponding higher order stresses are included in the balance laws, and the equation for the yield surface. Three different functional relationships, the power law, and those proposed by Wright and Batra, and Johnson and Cook are used to relate the effective strain rate to the effective stress and temperature. Effects of strain hardening of the material and elastic deformations are neglected. The homogeneous solution of the problem is perturbed and the stability of the problem linear in the perturbation variables is studied. Following Wright and Ockendon's postulate that the wavelength whose initial growth rate is maximum determines the minimum spacing between adjacent shear bands, the shear band spacing is computed. It is found that the minimum shear band spacing is very sensitive to the thermal softening coefficient/exponent, the material characteristic length and the nominal strain-rate. Approximate analytical expressions for the critical wave length for heat conducting nonpolar materials and locally adiabatic deformations of gradient dependent materials are also derived.     

Pharmacokinetics and biodistribution of genetically-engineered antibodies

Monoclonal antibodies (MAbs), because of their inherent specificity, are ideal targeting agents. They can be used to deliver radionuclides, toxins or cytotoxic drugs to a specific tissue or malignant cell populations. Intact immunoglobulin (IgG) molecules have several practical limitations of their pharmacology; their relatively large size of approximately 150,000 daltons leads to a slow clearance from the blood pool and the body resulting in significant exposure to normal organs with limited quantities delivered to tumors. The IgG molecule shows a relatively poor diffusion from the vasculature into and through the tumor. Attempts to modify the pharmacology of the Ig molecule have classically involved the use of proteases to generate F(ab')2 and Fab' fragments with molecular weights of approximately 100,000 and 50,000 daltons, respectively. Fv fragments of IgG are one of the smallest size functional modules of antibodies that retain high affinity binding of an antigen. Their smaller size, approximately 25,000 daltons, enables better tumor penetration and makes them potentially more useful than a whole antibody molecule for clinical applications. Molecular cloning and expression of the variable region genes of IgG has greatly facilitated the generation of engineered antibodies. A single-chain Fv (scFv) recombinant protein, prepared by connecting genes encoding for heavy-chain and light-chain variable regions at the DNA level by an appropriate oligonucleotide linker, clears from the blood at much faster rate than intact IgG. The scFv fragment can retain an antigen-binding affinity similar to that of a monovalent Fab' fragment; this however, represents a relative decrease in binding affinity when compared to intact antibodies. The scFv with its faster clearance and lower affinity results in a lower percent-injected dose localizing in tumors when compared to the divalent IgG molecule. This may be adequate for imaging but probably not for therapy. The valency of the MAb fragment is critical for the functional affinity of an antibody to a cell surface or a polymeric antigen. In attempts to generate multivalent forms of scFv molecules, non-covalently linked scFv dimeric and trimeric molecules, disulfide linked dimeric scFvs, as well as covalently linked chimeric scFvs have been studied. These multivalent scFvs generally have a higher functional affinity than the monovalent form resulting in better in vivo targeting. Another way to alter the pharmacology of the scFvs is to modify its net charge. Charge-modified scFvs with desired isoelectric points (pI), have been prepared by inserting negatively charged amino acids on the template of the variable region genes. This can help to overcome undesirable elevations in renal uptake seen with most antibody fragments. In conclusion, genetic manipulations of the immunoglobulin molecules are effective means of altering stability, functional affinity, pharmacokinetics, and biodistribution of the antibodies required for the generation of the "magic bullet".     

A numerical study of singularly perturbed generalized Burgers-Huxley equation using three-step Taylor-Galerkin method

In the present work, a numerical study has been carried out for the singularly perturbed generalized Burgers-Huxley equation using a three-step Taylor-Galerkin finite element method. A Burgers-Huxley equation represents the traveling wave phenomena. In singular perturbed problems, a very small positive parameter, ?, called the singular perturbation parameter is multiplied with the highest order derivative term. As this parameter tends towards zero, the problem exhibits boundary layers. The traditional methods fail to capture the boundary layers when ? becomes very small. In this paper a three-step Taylor-Galerkin finite element method is used to capture the boundary layers. The method is third-order accurate and has inbuilt upwinding. Stability analysis has been carried out and the numerical results show that the method is efficient in capturing the boundary layers.     

Measurement of Ambient Ammonia over the National Capital Region of Delhi,India

Mixing ratio of ambient ammonia (NH₃) was measured at various locations of the National Capital Region (NCR) of Delhi, India using a NH₃-analyzer during January 2010 to June 2012 in campaign mode. The present study has been carried out on campaign based measurement of mixing ratios of NH₃ and NO _x for short period of time over the NCR of Delhi represent the indicative values over the region. The average mixing ratio of ambient NH₃ was 20.9 ± 1.6 ppb during the period. The maximum average mixing ratio of ambient NH₃ (28.8 ± 3.0 ppb) was recorded in an industrial area surrounded by intensive vehicular traffic followed by an agricultural farm (27.5 ± 2.1 ppb), whereas the minimum (6.4 ± 1.2 ppb) was recorded in the semi-urban area. The diurnal trend of NH₃ depended on the ambient temperature at most of the sites and was affected by wind direction. Ambient NH₃ was correlated with the NO _x mixing ratio suggesting that the vehicular emission may be one of the sources of ambient NH₃ in the NCR of Delhi. However, long-term measurements of ambient NH₃ and their precursors will lead to seasonal variation of source apportionment over the NCR, Delhi, India.     

Pharmacokinetics of loratadine and pseudoephedrine following single and multiple doses of once- versus twice-daily combination tablet formulations in healthy adult males

The pharmacokinetic profiles of single and multiple doses of loratadine, descarboethoxyloratadine (DCL) (the major active metabolite of loratadine), and pseudoephedrine were determined in a randomized, open-label, two-way crossover study in 24 healthy men. Subjects received a single dose (day 1) and multiple doses (days 3 to 10) of a once-daily (QD) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLAR-ITIN-D 24 HOUR tablets), and a twice-daily (BID) formulation of loratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, with 60 mg in an immediate-release coating and 60 mg in the barrier-protected core (CLARITIN-D 12 HOUR tablets) in study sessions, each separated by a 10-day washout period. Both regimens were safe and well tolerated. On day 1, plasma loratadine, DCL, and pseudoephedrine concentrations were higher following the QD formulation than following the BID formulation, as expected. On day 10, loratadine and DCL maximum plasma concentration (Cmax) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulation; however, the values of the area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) for loratadine and DCL were equivalent (90% confidence interval [CI]: 83% to 110% for loratadine; 90% to 107% for DCL). On day 10, pseudoephedrine Cmax and AUC0-24 values were equivalent (90% CI for Cmax: 94% to 109%; for AUC: 91% to 106%) for the two formulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrine formulations produced equivalent loratadine and DCL AUC0-24 values and equivalent pseudoephedrine Cmax and AUC0-24 values following multiple dosing. The lower pseudoephedrine concentrations in the evening with the QD formulation may minimize the potential for insomnia in patients when compared with the BID formulation.     

Autonomic cloud resource provisioning and scheduling using meta-heuristic algorithm

We investigate that resource provisioning and scheduling is a prominent problem due to heterogeneity as well as dispersion of cloud resources. Cloud service providers are building more and more datacenters due to demand of high computational power which is a serious threat to environment in terms of energy requirement. To overcome these issues, we need an efficient meta-heuristic technique that allocates applications among the virtual machines fairly and optimizes the quality of services (QoS) parameters to meet the end user objectives. Binary particle swarm optimization (BPSO) is used to solve real-world discrete optimization problems but simple BPSO does not provide optimal solution due to improper behavior of transfer function. To overcome this problem, we have modified transfer function of binary PSO that provides exploration and exploitation capability in better way and optimize various QoS parameters such as makespan time, energy consumption, and execution cost. The computational results demonstrate that modified transfer function-based BPSO algorithm is more efficient and outperform in comparison with other baseline algorithm over various synthetic datasets.