Principal component analysis for minimal model identification of a noise-affected fermentation: application to streptokinase

Principal component analysis (PCA) has been applied to a fed-batch fermentation for the production of streptokinase to identify the variables which are essential to formulate an adequate model. To mimic an industrial situation, Gaussian noise was introduced in the feed rate of the substrate. Both in the presence and in the absence of noise, the same five variables out of seven were selected by PCA. The minimal model trained separately without and with noise was able to predict satisfactorily the course of the fermentation for a condition not employed in training. These observations attest the suitability of PCA to formulate minimal models for industrial scale fermentations.     

Detection of microRNAs in dried serum blots

We observed the preservation of microRNAs in unrefrigerated dried serum blots. Preservation was not adversely affected by drying or storing at 37, 45, or 60 °C instead of room temperature, but it was harmed when blots were dried incompletely before storage. Preservation of microRNAs in serum was not diminished if, instead of being kept frozen at −80 °C, it was stored as dried blots at room temperature for 5 months or at 37 °C for 4 weeks. Thus, dried blots can be a convenient and safer way to save, transport, and store serum for microRNA assays.     

Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response

Tumor necrosis factor (TNF) is a multipotential cytokine known to regulate the growth of a wide variety of normal and tumor cells. It has been shown that the density of cells in culture can modulate the growth regulatory activities of TNF, the mechanism of which, however, is not understood. In this report, we investigated the effect of cell density on the expression of TNF receptors. The receptors were examined on epithelial cells (e.g., HeLa), which primarily express the p60 form, and on myeloid cells (e.g., HL-60) known to express mainly the p80 form. We observed that binding of TNF to both cell lines decreased with increase in cell density. Scatchard analysis of binding on HeLa and HL-60 cells revealed a 4- to 5-fold reduction in the number of TNF receptors without any significant change in receptor affinity in both cell types at high density. The decrease in TNF receptor numbers at high cell density was also observed in several other epithelial and myeloid cell lines. The downmodulation at high cell density was unique to TNF receptors, since minimum change in other cell surface proteins was observed as revealed by fluorescent activated cell sorter analysis. Neutralization of binding with antibodies specific to each type of the receptors revealed that both the p60 and p80 forms of the TNF receptor were equally downmodulated. A decrease in leucine incorporation into proteins was observed with increase in cell density, suggesting a reduction in protein synthesis. Since inhibition of protein synthesis by cycloheximide also leads to a decrease in TNF receptors, it is possible that the density-dependent reduction in TNF receptor number is due to an overall decrease in protein synthesis. The density-dependent decrease in TNF receptors was accompanied by a decrease in intracellular reduced glutathione levels. A reduction in the number of receptors on TNF sensitive tumor cells induced by cell-density correlated with increase in resistance to the cytokine.     

Spectral analysis of the effect of inflow noise on a fed-batch fermentation for recombinant β-galactosidase

The fermentative production of β-galactosidase from Escherichia coli CSH50 containing the plasmid pOU140 is mechanistically complex and difficult to model in a nonideal bioreactor. A spectral analysis has been done for a fed-batch fermentation with Gaussian disturbances in the feed stream. Inflow noise converts a smooth operation into aperiodic motion, as observed in some chemical reactions also. The disturbances also cause significant differences in the frequency responses of intra-cellular (plasmid DNA and β-galactosidase) and extra-cellular (concentration and mass fraction of recombinant cells) variables, whose implications are discussed.     

Determination of the relative and absolute stereochemistry of a potent and α1A-selective adrenoceptor antagonist

The binding affinities and selectivities of antagonists Figure 1 and Scheme 2 for the α_1A-adrenoceptor are dependent on the stereochemical orientation of the groups at the C-4 and C-5 positions of the oxazolidinone ring. The unambiguous assignment of the relative and absolute configurations of the diastereomers of SNAP 7915 (Figure 1 and Scheme 2) is reported.     

Effect of picroliv on low density lipoprotein receptor binding of rat hepatocytes in hepatic damage induced by paracetamol.

Picroliv from root and rhizome of Picrorhiza kurroa showed reversal of low density lipoprotein (LDL) binding to paracetamol-induced damaged hepatocytes of rats. Changes in levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, conjugated dienes and lipids of hepatocytes were significantly prevented by picroliv at different doses. The effect of picroliv on enzyme levels, LDL receptor binding and lipids in damaged hepatocytes was found to be comparable to silymarin, a known hepatoprotective agent.     

Analysis of bifurcations in continuous fermentation using recombinant microorganisms with delayed responses

When the feed rate to a fermenter is varied periodically in order to favor the growth of plasmid-containing cells, a transition may occur from the starting stationary state to another state. The resulting state may be constant or oscillatory. A generalised model based on the adaption times of plasmid-free and plasmid-harboring cells has been used. Analytical conditions have been derived for bifurcation from one nonoscillatory state to another or to an oscillatory state (Hopf bifurcation). The frequency of oscillation is shown to have an upper bound, which can be controlled by manipulating certain process parameters. The production of tryptophan synthetase by the plasmid pPLc23trpAl in E. coli is used as an example to determine the nature of the Hopf bifurcations.     

Crocodilian Nest in a Late Cretaceous Sauropod Hatchery from the Type Lameta Ghat Locality,Jabalpur, India

The well-known Late Cretaceous Lameta Ghat locality (Jabalpur, India) provides a window of opportunity to study a large stable, near shore sandy beach, which was widely used by sauropod dinosaurs as a hatchery. In this paper, we revisit the eggs and eggshell fragments previously assigned to lizards from this locality and reassign them to crocodylomorphs. Several features point to a crocodilian affinity, including a subspherical to ellipsoidal shape, smooth, uneven external surface, discrete trapezoid shaped shell units with wide top and narrow base, basal knobs and wedge shaped crystallites showing typical inverted triangular extinction under crossed nicols. The crocodylomorph eggshell material presented in this paper adds to the skeletal data of these most probably Cretaceous-Eocene dryosaurid crocodiles.     

Antihistaminic activity of quinethindole: a 2-substituted pyrazinopyridoindole derivative.

Quinethindole, a 2-substituted pyrazinopyridoindole, showed specific antihistaminic (H1) activity in various in vivo and in vitro test models. It also inhibited antigen-induced contraction of ileum of sensitized guinea pig. The antihistaminic activity was of competitive nature.