Fully semiparametric Bayesian approach for modeling survival data with cure fraction

In this paper, we consider a piecewise exponential model (PEM) with random time grid to develop a full semiparametric Bayesian cure rate model. An elegant mechanism enjoying several attractive features for modeling the randomness of the time grid of the PEM is assumed. To model the prior behavior of the failure rates of the PEM we assume a hierarchical modeling approach that allows us to control the degree of parametricity in the right tail of the survival curve. Properties of the proposed model are discussed in detail. In particular, we investigate the impact of assuming a random time grid for the PEM on the estimation of the cure fraction. We further develop an efficient collapsed Gibbs sampler algorithm for carrying out posterior computation. A Bayesian diagnostic method for assessing goodness of fit and performing model comparisons is briefly discussed. Finally, we illustrate the usefulness of the new methodology with the analysis of a melanoma clinical trial that has been discussed in the literature.     

Human eosinophil-derived neurotoxin: involvement of a putative non-catalytic phosphate-binding subsite in its catalysis

Human eosinophil-derived neurotoxin (EDN) or RNase 2, found in the non-core matrix of eosinophils is a ribonuclease belonging to the Ribonuclease A superfamily. EDN manifests a number of bioactions including neurotoxic and antiviral activities, which are dependent on its ribonuclease activity. The core of the catalytic site of EDN contains various base and phosphate-binding subsites. Unlike many members of the RNase A superfamily, EDN contains an additional non-catalytic phosphate-binding subsite, P₋₁. Although RNase A also contains a P₋₁ subsite, the composition of the site in EDN and RNase A is different. In the current study we have generated site-specific mutants to study the role of P₋₁ subsite residues Arg³⁶, Asn³⁹, and Gln⁴⁰ of EDN in its catalytic activity. The individual mutation of Arg³⁶, Asn ³⁹, and Gln⁴⁰ resulted in a reduction in the catalytic activity of EDN on poly(U) and poly(C). However, there was no change in the activities on yeast tRNA and dinucleotide substrates. The study shows that the P₋₁ subsite is crucial for the ribonucleolytic activity of EDN on polymeric RNA substrates. Deepa Sikriwal and Divya Seth contributed equally to this work.     

Effects of Temperature and Dietary Lipids on Phospholipid Fatty Acids and Membrane Fluidity in Steinernema carpocapsae

The phospholipid composition of Steinernema carpocapsae was studied in relation to diet and culture temperature. When reared at 18 and 27.5 C on Galleria mellonella or on an artificial diet supplemented with lard, linseed oil, or fish oil as lipid sources, nematode phospholipids contained an abundance of 20-carbon polyunsaturated fatty acids, with eicosapentaenoic acid (20:5(n - 3)) predominant, regardless of the fatty acid composition of the diet. Because the level of linolenic acid (18:3(n - 3)) in nematode phospholipids was very low and because eicosapentaenoic acid was present even when its precursor (linolenic acid) was undetectable in the diet, S. carpocapsae likely produces n - 3 polyunsaturated fatty acids by de novo biosynthesis, a pathway seldom reported in eukaryotic animals. Reduction of growth temperature from 25 to 18 C increased the proportion of 20:5(n - 3) but not other polyunsaturated fatty acids. A fluorescence polarization technique revealed that vesicles produced from phospholipids of nematodes reared at 18 C were less ordered than those from nematodes reared at 27.5 C, especially in the outermost region of the bilayer. Dietary fish oil increased fluidity in the outermost region but increased rigidity in deeper regions. Therefore, S. carpocapsae appears to modify its membrane physical state in response to temperature, and eicosapentaenoic acid may be involved in this response. The results also indicate that nematode membrane physical state can be modified dietarily, possibly to the benefit of host-finding or survival of S. carpocapsae at low temperatures.     

Continuous production of high-purity fructooligosaccharides and ethanol by immobilized Aspergillus japonicus and Pichia heimii

High-purity fructooligosaccharides (FOS) were produced from sucrose by an innovative process incorporating immobilized Aspergillus japonicus and Pichia heimii cells. Intracellular FTase of A. japonicus converted sucrose into FOS and glucose, and P. heimii fermented glucose mainly into ethanol. The continuous production of FOS was carried out using a tanks-in-series bioreactor consisting of three stirred tanks. When a solution composed of 1 g L^?1 yeast extract and 300 g L^?1 sucrose was fed continuously to the bioreactor at a dilution rate of 0.1 h^?1, FOS at a purity of up to 98.2 % could be achieved and the value-added byproduct ethanol at 79.6 g L^?1 was also obtained. One gram of sucrose yielded 0.62 g FOS and 0.27 g ethanol. This immobilized dual-cell system was effective for continuous production of high-purity FOS and ethanol for as long as 10 days.     

121 Influence of changes in DNA conformation on thermodynamic contribution during interaction of human genomic DNA and its mutant with anticancer drugs

Isothermal calorimetry (ITC) is efficient in characterizing and recognizing both high affinity and low affinity intermolecular interactions quickly and accurately. Adriamycin (ADR) and daunomycin (DNM) are the two anticancer drugs whose activity is achieved mainly by intercalation with DNA. During chemotherapy, normal human genomic DNA and mutated DNA from K562 leukemic cells show different thermodynamic properties and binding affinities on interaction with ADR and DNM when followed by ITC. Normal DNA shows more than one step in kinetic analysis, which could be attributed to outside binding, intercalation and reshuffling as suggested by Chaires et al. (1985); whereas K562 DNA fits a different binding pattern with higher binding affinities (by one order or more) compared to normal DNA. Structural properties of the interaction were followed by laser Raman spectroscopy, where difference in structure was apparent from the shifts in marker B DNA Raman bands (Ling et al., 2005). A correlation of thermodynamic contribution and structural data reveals step wise changes in normal genomic DNA conformation on drug binding. The overall structural change is higher in normal DNA–DNM interaction suggesting a partial B to A transition on drug binding. Such large changes were not observed for K562 DNA–DNM interaction which showed B to A transition properties in native from itself corroborating with our earlier findings (Ghosh et al., 2012).     

Evolution of chromosome number in grasshoppers (Orthoptera: Caelifera: Acrididae)

Organisms Diversity & Evolution - Orthoptera have some of the largest genomes of all insects. At the same time, the architecture of their genomes remains poorly understood. Comparative...