Yeast Bax Inhibitor, Bxi1p, Is an ER-Localized Protein that Links the Unfolded Protein Response and Programmed Cell Death in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e

Bax inhibitor-1 (BI-1) is an anti-apoptotic gene whose expression is upregulated in a wide range of human cancers. Studies in both mammalian and plant cells suggest that the BI-1 protein resides in the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by ER stress. It is thought to act via a mechanism involving altered calcium dynamics. In this paper, we provide evidence that the Saccharomyces cerevisiae protein encoded by the open reading frame, YNL305C, is a bona fide homolog for BI-1. First, we confirm that yeast cells from two different strain backgrounds lacking YNL305C, which we have renamed BXI1, are more sensitive to heat-shock induced cell death than wildtype controls even though they have indistinguishable growth rates at 30°C. They are also more susceptible both to ethanol-induced and to glucose-induced programmed cell death. Significantly, we show that Bxi1p-GFP colocalizes with the ER localized protein Sec63p-RFP. We have also discovered that Δbxi1 cells are not only more sensitive to drugs that induce ER stress, but also have a decreased unfolded protein response as measured with a UPRE-lacZ reporter. Finally, we have discovered that deleting BXI1 diminishes the calcium signaling response in response to the accumulation of unfolded proteins in the ER as measured by a calcineurin-dependent CDRE-lacZ reporter. In toto, our data suggests that the Bxi1p, like its metazoan homologs, is an ER-localized protein that links the unfolded protein response and programmed cell death

Double-resonant fast particle-wave interaction

In future fusion devices fast particles must be well confined in order to transfer their energy to the background plasma. Magnetohydrodynamic instabilities like Toroidal Alfv\'en Eigenmodes or core-localized modes such as Beta Induced Alfv\'en Eigenmodes and Reversed Shear Alfv\'en Eigenmodes, both driven by fast particles, can lead to significant losses. This is observed in many ASDEX Upgrade discharges. The present study applies the drift-kinetic HAGIS code with the aim of understanding the underlying resonance mechanisms, especially in the presence of multiple modes with different frequencies. Of particular interest is the resonant interaction of particles simultaneously with two different modes, referred to as 'double-resonance'. Various mode overlapping scenarios with different q profiles are considered. It is found that, depending on the radial mode distance, double-resonance is able to enhance growth rates as well as mode amplitudes significantly. Surprisingly, no radial mode overlap is necessary for this effect. Quite the contrary is found: small radial mode distances can lead to strong nonlinear mode stabilization of a linearly dominant mode.Comment: 12 pages, 11 figures; Nuclear Fusion 52 (2012

Firm Size and the Information Content of Over-the-Counter Common Stock Offerings

We examine the announcement period of stock returns for 179 over-the-counter (OTC) firms that issue common stock to reduce nonconvertible debt. We find that small OTC firms experience returns that are significantly more negative than large OTC firms. Regression tests reveal that firm size is a significant factor in accounting for stock returns. Other tests establish as firm size a dominant effect. Our support for a firm size effect is consistent with a differential information effect given that firm size is positively related to the amount of information available about firms