Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol(-/-) embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol(-/-) mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphe nucleus and the trochlear motor nucleus are absent in mol(-/-) embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins

Effects of calorie restriction on life span of microorganisms

Calorie restriction (CR) in microorganisms such as budding and fission yeasts has a robust and well-documented impact on longevity. In order to efficiently utilize the limited energy during CR, these organisms shift from primarily fermentative metabolism to mitochondrial respiration. Respiration activates certain conserved longevity factors such as sirtuins and is associated with widespread physiological changes that contribute to increased survival. However, the importance of respiration during CR-mediated longevity has remained controversial. The emergence of several novel metabolically distinct microbial models for longevity has enabled CR to be studied from new perspectives. The majority of CR and life span studies have been conducted in the primarily fermentative Crabtree-positive yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, but studies in primarily respiratory Crabtree-negative yeast and obligate aerobes can offer complementary insight into the more complex mammalian response to CR. Not only are microorganisms helping characterize a conserved cellular mechanism for CR-mediated longevity, but they can also directly impact mammalian metabolism as part of the natural gut flora. Here, we discuss the contributions of microorganisms to our knowledge of CR and longevity at the level of both the cell and the organism

Steam drum process dynamics and level control of a pressure tube BWR

The Advanced Heavy Water Reactor (AHWR) is a pressure tube type light water cooled heavy water moderated Boding Water Reactor (BWR) with natural circulation at all power levels It has parallel inter connected loops with 452 boding channels in the Main Heat Transport (MHT) system configuration These multiple (four) interconnected loops influence the Steam Drum (SD) level control adversely Such a behavior has not been reported in the open literature The M HT configuration has been chosen based on comprehensive overall design requirements and certain Postulated Initiated Events (PIEs) This does not allow the partitioning of the Common Reactor Inlet Header (CRIH If partitioning of the CRIH into four segments is allowed then, it will make each loop independent Then the SD level control problems subside as the unaccounted interaction among the loops is eliminated It has also been observed that the open loop response is stable, non-oscillatory and non diverging for a step change in the feed flow rates A conventional individual 3 element SD level controller cannot account for the highly coupled and interacting behaviors, of the four loops and SD levels To overcome these interactions It is proposed to inter connect all the four steam drums in the liquid and vapor regions respectively The influence of the interconnect configuration and the level controller are studied in detail to find a robust solution The response obtained for unsymmetrical core power disturbances shows that the SD levels do not diverge and quickly settle to the set points assigned with SD interconnect The proposed scheme also works well for most of the PIEs considere

Effect of Loop Configuration on Steam Drum Level Control for a Multiple Drum Interconnected Loops Pressure Tube Type Boiling Water Reactor

For AHWR (Advanced Heavy Water Reactor), a pressure tube type Boiling Water Reactor (BWR) with parallel inter-connected loops, the Steam Drum (SD) level control is closely related to Main Heat Transport (MHT) coolant inventory and sustained heat removal through natural circulation, hence overall safety of the power plant. The MHT configuration with multiple (four) interconnected loops influences the SD level control in a manner which has not been previously addressed. The MHT configuration has been chosen based on comprehensive overall design requirements and certain Postulated Initiated Event (PIEs) for Loss of Coolant Accident (LOCA), which postulates a double ended break in the four partitioned Emergency Core Cooling System (ECCS) header. A conventional individual three-element SD level controller can not account for the highly coupled and interacting behaviors, of the four SD levels. An innovative three-element SD level control scheme is proposed to overcome this situation. The response obtained for a variety of unsymmetrical disturbances shows that the SD levels do not diverge and quickly settle to the various new set points assigned. The proposed scheme also leads to enhanced safety margins for most of the PIEs considered with a little influence on the 100% full power steady-state design conditions