69,112 research outputs found

    Regulation of vacuolar H+-ATPase activity by the Cdc42 effector Ste20 in Saccharomyces cerevisiae

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    In the budding yeast Saccharomyces cerevisiae, the Cdc42 effector Ste20 plays a crucial role in the regulation of filamentous growth, a response to nutrient limitation. Using the split-ubiquitin technique, we found that Ste20 forms a complex with Vma13, an important regulatory subunit of vacuolar H(+)-ATPase (V-ATPase). This protein-protein interaction was confirmed by a pulldown assay and coimmunoprecipitation. We also demonstrate that Ste20 associates with vacuolar membranes and that Ste20 stimulates V-ATPase activity in isolated vacuolar membranes. This activation requires Ste20 kinase activity and does not depend on increased assembly of the V1 and V0 sectors of the V-ATPase, which is a major regulatory mechanism. Furthermore, loss of V-ATPase activity leads to a strong increase in invasive growth, possibly because these cells fail to store and mobilize nutrients efficiently in the vacuole in the absence of the vacuolar proton gradient. In contrast to the wild type, which grows in rather small, isolated colonies on solid medium during filamentation, hyperinvasive vma mutants form much bigger aggregates in which a large number of cells are tightly clustered together. Genetic data suggest that Ste20 and the protein kinase A catalytic subunit Tpk2 are both activated in the vma13Δ strain. We propose that during filamentous growth, Ste20 stimulates V-ATPase activity. This would sustain nutrient mobilization from vacuolar stores, which is beneficial for filamentous growth.The project was supported by Deutsche Forschungsgemeinschaft grant HO 2098/3 to T.H. and NIH grant R01 GM50322 to P.M.K

    Effect of blood's velocity on blood resistivity

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    Blood resistivity is an important quantity whose value influences the results of various methods used in the study of heart and circulation. In this paper, the relationship between blood resistivity and velocity of blood flow was evaluated and analyzed based upon a probe using six-ring electrodes and a circulatory model. The experimental results indicated that the change in blood resistivity was only ±1.1% when the velocity of blood flow changed from 2.83 to 40 cm/s and it rose to 23% when the velocity was lower than 2.83 cm/s

    Local and global limits on visual processing in schizophrenia.

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    Schizophrenia has been linked to impaired performance on a range of visual processing tasks (e.g. detection of coherent motion and contour detection). It has been proposed that this is due to a general inability to integrate visual information at a global level. To test this theory, we assessed the performance of people with schizophrenia on a battery of tasks designed to probe voluntary averaging in different visual domains. Twenty-three outpatients with schizophrenia (mean age: 40±8 years; 3 female) and 20 age-matched control participants (mean age 39±9 years; 3 female) performed a motion coherence task and three equivalent noise (averaging) tasks, the latter allowing independent quantification of local and global limits on visual processing of motion, orientation and size. All performance measures were indistinguishable between the two groups (ps>0.05, one-way ANCOVAs), with one exception: participants with schizophrenia pooled fewer estimates of local orientation than controls when estimating average orientation (p = 0.01, one-way ANCOVA). These data do not support the notion of a generalised visual integration deficit in schizophrenia. Instead, they suggest that distinct visual dimensions are differentially affected in schizophrenia, with a specific impairment in the integration of visual orientation information

    Plural Policing and the Challenge of Democratic Accountability

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    This chapter explores the accountability of the mixed economy of public and private policing in the England and Wales. Its starting point is the recognition that a variety of public, private and hybrid actors are engaged in the authorization and provision of policing. As a consequence, the article does not restrict its analytical gaze to how state power, as deployed by police forces, is made accountable. Rather, it considers how, under market conditions, networks of plural policing can be governed according to, and accommodated within, a set of democratic principles. In so doing, it is argued that ‘local security networks’ comprising state, civil society and market actors, and whose governance and accountability mechanisms frequently stand outside of extant political structures, raise specific challenges if they are to be governed not only effectively but also democratically. The article proceeds to consider options for bringing democratically accountable governance to plural policing networks

    How Officers Create Guardianship: An Agent-based Model of Policing

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    Crime is a complex phenomenon, emerging from the interactions of offenders, victims, and their environment, and in particular from the presence or absence of capable guardians. Researchers have historically struggled to understand how police officers create guardianship. This presents a challenge because, in order to understand how to advise the police, researchers must have an understanding of how the current system works. The work presents an agent-based model that simulates the movement of police vehicles, using a record of real calls for service and real levels of police staffing in spatially explicit environments to emulate the demands on the police force. The GPS traces of the simulated officers are compared with real officer movement GPS data in order to assess the quality of the generated movement patterns. The model represents an improvement on existing standards of police simulation, and points the way toward more nuanced understandings of how police officers influence the criminological environment

    Numerical investigation of the conditioning for plane wave discontinuous Galerkin methods

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    We present a numerical study to investigate the conditioning of the plane wave discontinuous Galerkin discretization of the Helmholtz problem. We provide empirical evidence that the spectral condition number of the plane wave basis on a single element depends algebraically on the mesh size and the wave number, and exponentially on the number of plane wave directions; we also test its dependence on the element shape. We show that the conditioning of the global system can be improved by orthogonalization of the local basis functions with the modified Gram-Schmidt algorithm, which results in significantly fewer GMRES iterations for solving the discrete problem iteratively.Comment: Submitted as a conference proceeding; minor revisio

    Particle Physics Probes Of Extra Spacetime Dimensions

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    The possibility that spacetime is extended beyond the familiar 3+1-dimensions has intrigued physicists for a century. Indeed, the consequences of a dimensionally richer spacetime would be profound. Recently, new theories with higher dimensional spacetimes have been developed to resolve the hierarchy problem in particle physics. These scenarios make distinct predictions which allow for experiment to probe the existence of extra dimensions in new ways. We review the conceptual framework of these scenarios, their implications in collider and short-range gravity experiments, their astrophysical and cosmological effects, as well as the constraints placed on these models from present data.Comment: Submitted to Annual Review of Nuclear and Particle Science, 29 page
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