Trans-SNARE interactions elicit Ca2+ efflux from the yeast vacuole lumen

Ca2+ transients trigger many SNARE-dependent membrane fusion events. The homotypic fusion of yeast vacuoles occurs after a release of lumenal Ca2+. Here, we show that trans-SNARE interactions promote the release of Ca2+ from the vacuole lumen. Ypt7p–GTP, the Sec1p/Munc18-protein Vps33p, and Rho GTPases, all of which function during docking, are required for Ca2+ release. Inhibitors of SNARE function prevent Ca2+ release. Recombinant Vam7p, a soluble Q-SNARE, stimulates Ca2+ release. Vacuoles lacking either of two complementary SNAREs, Vam3p or Nyv1p, fail to release Ca2+ upon tethering. Mixing these two vacuole populations together allows Vam3p and Nyv1p to interact in trans and rescues Ca2+ release. Sec17/18p promote sustained Ca2+ release by recycling SNAREs (and perhaps other limiting factors), but are not required at the release step itself. We conclude that trans-SNARE assembly events during docking promote Ca2+ release from the vacuole lumen

High Performance P3M N-body code: CUBEP3M

This paper presents CUBEP3M, a publicly-available high performance cosmological N-body code and describes many utilities and extensions that have been added to the standard package. These include a memory-light runtime SO halo finder, a non-Gaussian initial conditions generator, and a system of unique particle identification. CUBEP3M is fast, its accuracy is tuneable to optimize speed or memory, and has been run on more than 27,000 cores, achieving within a factor of two of ideal weak scaling even at this problem size. The code can be run in an extra-lean mode where the peak memory imprint for large runs is as low as 37 bytes per particles, which is almost two times leaner than other widely used N-body codes. However, load imbalances can increase this requirement by a factor of two, such that fast configurations with all the utilities enabled and load imbalances factored in require between 70 and 120 bytes per particles. CUBEP3M is well designed to study large scales cosmological systems, where imbalances are not too large and adaptive time-stepping not essential. It has already been used for a broad number of science applications that require either large samples of non-linear realizations or very large dark matter N-body simulations, including cosmological reionization, halo formation, baryonic acoustic oscillations, weak lensing or non-Gaussian statistics. We discuss the structure, the accuracy, known systematic effects and the scaling performance of the code and its utilities, when applicable.Comment: 20 pages, 17 figures, added halo profiles, updated to match MNRAS accepted versio

The association of statin use after cancer diagnosis with survival in pancreatic cancer patients: a SEER-medicare analysis.

BackgroundPancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).MethodsWe analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).ResultsOverall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.ConclusionsWe found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC

The distribution and re-distribution of income of selfemployed as freelancers and entrepreneurs in Europe

The economic transformations of modern industrial societies have changed the labor markets in terms of industrial relations and occupational structure. The transformation of the traditional welfare state, the deregulation of the labor markets, the technological change and the reorganization of industrial structures influenced strongly the attitude of individuals towards their preferred labor contract. The structural change of the occupational structure was one of the results of this tendency. In particular the self-employed and freelancers have been affected and are a driving factor of labor market changings. On the one side the value of autonomy regarding industrial relations is becoming more important for employees. On the other side employers want to get rid of social security contributions. As a result the multitudinousness of these professions increased. The increasing varieties of occupations among the self-employed and freelancers influenced strongly their income distribution. Recent studies for Germany have shown a great dispersion and a heterogeneous structure of earnings in particular of freelancers (liberal professions) and self-employed. Though there are a variety of international income distribution studies, but – as to the best to our knowledge – no study focusing on the selfemployed and freelancers within the total labor force. In our study we concentrate on the income distribution of self-employed and freelancers in different European countries. Based on the Luxembourg Income Study (LIS) we analyze five different European countries and the United States structured by different types of welfare states according to Esping Anderson. We analyze income distributional aspects, an occupational decomposition à la Shorrocks, and re-distributional effects of the tax and transfer systems

The Timing of Daily Demand for Goods and Services – Multivariate Probit Estimates and Microsimulation Results for an Aged Population with German Time Use Diary Data

Though consumption research provides a broad spectrum of theoretical and empirical founded results, studies based on a daily focus are missing. Knowledge about the individual timing of daily demand for goods and services, opens – beyond a genuine contribution to consumption research – interesting societal and macro economic as well as individual personal and firm perspectives: it is important for an efficient timely coordination of supply and demand in the timing perspective as well as for a targeted economic, social and societal policy for a better support of the every day coordination of life. Last not least, the individual daily public and private living situations will be visible, which are of particular importance for the social togetherness in family and society. Our study contributes to the timing of daily consumption for goods and services with an empirical founded microanalysis on the basis of more than 37.000 individual time use diaries of the nationwide Time Budget Survey of the German Federal Statistical Office 2001/02. We describe the individual timing of daily demand for goods and services for important socio-demographic groups like for women and men, the economic situation with income poverty and daily working hour arrangements. The multivariate microeconometric explanation of the daily demand for goods and services is based on a latent utility maximizing approach over a day. We estimate an eight equation Multivariate/Simultaneous Probit Model, which allows the decision for multiple consumption activities in more than one time period a day. The estimates quantify effects on the timing of daily demand by individual socio-economic variables, which encompasses, personal, household, regional characteristics as well as daily working hour arrangements within a flexible labour market. The question about individual effects of an aged society on the timing of daily demand for goods and services is analyzed with our microsimulation model ServSim and a population forecast for 2020 by the German Federal Statistical Office. Main result: There are significant differences in explaining the timing of daily demand for goods compared to services on the one hand and in particular for different daily time periods. The conclusion: without the timing aspects an important and significant dimension for understanding individual consumption behaviour and their impacts on other individual living conditions would be missing