The casein kinases Yck1p and Yck2p act in the secretory pathway, in part, by regulating the Rab exchange factor Sec2p.

Sec2p is a guanine nucleotide exchange factor that activates Sec4p, the final Rab GTPase of the yeast secretory pathway. Sec2p is recruited to secretory vesicles by the upstream Rab Ypt32p acting in concert with phosphatidylinositol-4-phosphate (PI(4)P). Sec2p also binds to the Sec4p effector Sec15p, yet Ypt32p and Sec15p compete against each other for binding to Sec2p. We report here that the redundant casein kinases Yck1p and Yck2p phosphorylate sites within the Ypt32p/Sec15p binding region and in doing so promote binding to Sec15p and inhibit binding to Ypt32p. We show that Yck2p binds to the autoinhibitory domain of Sec2p, adjacent to the PI(4)P binding site, and that addition of PI(4)P inhibits Sec2p phosphorylation by Yck2p. Loss of Yck1p and Yck2p function leads to accumulation of an intracellular pool of the secreted glucanase Bgl2p, as well as to accumulation of Golgi-related structures in the cytoplasm. We propose that Sec2p is phosphorylated after it has been recruited to secretory vesicles and the level of PI(4)P has been reduced. This promotes Sec2p function by stimulating its interaction with Sec15p. Finally, Sec2p is dephosphorylated very late in the exocytic reaction to facilitate recycling

Computing the distribution of the maximum in balls-and-boxes problems, with application to clusters of disease cases

We present a rapid method for the exact calculation of the cumulative distribution function of the maximum of multinomially distributed random variables. The method runs in time $O(mn)$, where $m$ is the desired maximum and $n$ is the number of variables. We apply the method to the analysis of two situations where an apparent clustering of cases of a disease in some locality has raised the possibility that the disease might be communicable, and this possibility has been discussed in the recent literature. We conclude that one of these clusters may be explained on purely random grounds, whereas the other may not

What Moser Could Have Asked: Counting Hamilton Cycles in Tournaments

Moser asked for a construction of explicit tournaments on $n$ vertices having at least $(\frac{n}{3e})^n$ Hamilton cycles. We show that he could have asked for rather more

A search for X-ray polarization in cosmic X-ray sources

Fifteen strong X-ray sources were observed by the X-ray polarimeters on board the OSO-8 satellite from 1975 to 1978. The final results of this search for X-ray polarization in cosmic sources are presented in the form of upper limits for the ten sources which are discussed elsewhere. These limits in all cases are consistent with a thermal origin for the X-ray emission

Spectroscopy from 2 to 200 keV

The astrophysical processes responsible for line and continuum emission in the spectra range 2 keV to 200 keV are examined from the viewpoint of designing a spectrometer which would operate in this regime. Phenomena considered include fluorescent line radiation in X-ray binaries, magnetically shifted iron lines and cyclotron emission from neutron star surfaces, line emission from cosmically abundant elements in thermal plasmas, and nuclear deexcitation lines in fresh nucleosynthetically produced matter. An instrument consisting of a approximately 10 sq cm array of planar germanium detectors surrounded by a large sodium-iodide anticoincidence shield is described and projected background rates and sensitivities are considered. A sample observing program for a two-day shuttle-based mission is included as an example of the wide range of scientific questions which could be addressed by such an instrument

Comparative study of different scattering geometries for the proposed Indian X-ray polarization measurement experiment using Geant4

Polarization measurements in X-rays can provide unique opportunity to study the behavior of matter and radiation under extreme magnetic fields and extreme gravitational fields. Unfortunately, over past two decades, when X-ray astronomy witnessed multiple order of magnitude improvement in temporal, spatial and spectral sensitivities, there is no (or very little) progress in the field of polarization measurements of astrophysical X-rays. Recently, a proposal has been submitted to ISRO for a dedicated small satellite based experiment to carry out X-ray polarization measurement, which aims to provide the first X-ray polarization measurements since 1976. This experiment will be based on the well known principle of polarization measurement by Thomson scattering and employs the baseline design of a central low Z scatterer surrounded by X-ray detectors to measure the angular intensity distribution of the scattered X-rays. The sensitivity of such experiment is determined by the collecting area, scattering and detection efficiency, X-ray detector background, and the modulation factor. Therefore, it is necessary to carefully select the scattering geometry which can provide the highest modulation factor and thus highest sensitivity within the specified experimental constraints. The effective way to determine optimum scattering geometry is by studying various possible scattering geometries by means of Monte Carlo simulations. Here we present results of our detailed comparative study based on Geant4 simulations of five different scattering geometries which can be considered within the weight and size constraints of the proposed small satellite based X-ray polarization measurement experiment.Comment: 14 pages, 6 figures, accepted for publication in "Nuclear Inst. and Methods in Physics Research, A