220 research outputs found

    Cln5 represents a new type of cysteine-basedS-depalmitoylase linked to neurodegeneration

    Get PDF
    Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer’s disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins

    DCMIP2016: a review of non-hydrostatic dynamical core design and intercomparison of participating models

    Get PDF
    Atmospheric dynamical cores are a fundamental component of global atmospheric modeling systems and are responsible for capturing the dynamical behavior of the Earth's atmosphere via numerical integration of the Navier-Stokes equations. These systems have existed in one form or another for over half of a century, with the earliest discretizations having now evolved into a complex ecosystem of algorithms and computational strategies. In essence, no two dynamical cores are alike, and their individual successes suggest that no perfect model exists. To better understand modern dynamical cores, this paper aims to provide a comprehensive review of 11 non-hydrostatic dynamical cores, drawn from modeling centers and groups that participated in the 2016 Dynamical Core Model Intercomparison Project (DCMIP) workshop and summer school. This review includes a choice of model grid, variable placement, vertical coordinate, prognostic equations, temporal discretization, and the diffusion, stabilization, filters, and fixers employed by each syste

    BAERLIN2014 -The influence of land surface types on and the horizontal heterogeneity of air pollutant levels in Berlin

    Get PDF
    Urban air quality and human health are among the key aspects of future urban planning. In order to address pollutants such as ozone and particulate matter, efforts need to be made to quantify and reduce their concentrations. One important aspect in understanding urban air quality is the influence of urban vegetation which may act as both emitter and sink for trace gases and aerosol particles. In this context, the "Berlin Air quality and Ecosystem Research: Local and long-range Impact of anthropogenic and Natural hydrocarbons 2014" (BAERLIN2014) campaign was conducted between 2 June and 29 August in the metropolitan area of Berlin and Brandenburg, Germany. The predominant goals of the campaign were (1) the characterization of urban gaseous and particulate pollution and its attribution to anthropogenic and natural sources in the region of interest, especially considering the connection between biogenic volatile organic compounds and particulates and ozone; (2) the quantification of the impact of urban vegetation on organic trace gas levels and the presence of oxidants such as ozone; and (3) to explain the local heterogeneity of pollutants by defining the distribution of sources and sinks relevant for the interpretation of model simulations. In order to do so, the campaign included stationary measurements at urban background station and mobile observations carried out from bicycle, van and airborne platforms. This paper provides an overview of the mobile measurements (Mobile BAERLIN2014) and general conclusions drawn from the analysis. Bicycle measurements showed micro-scale variations of temperature and particulate matter, displaying a substantial reduction of mean temperatures and particulate levels in the proximity of vegetated areas compared to typical urban residential area (background) measurements. Van measurements extended the area covered by bicycle observations and included continuous measurements of O3, NOx, CO, CO2 and point-wise measurement of volatile organic compounds (VOCs) at representative sites for traffic- and vegetation-affected sites. The quantification displayed notable horizontal heterogeneity of the short-lived gases and particle number concentrations. For example, baseline concentrations of the traffic-related chemical species CO and NO varied on average by up to ±22.2 and ±63.5 %, respectively, on the scale of 100 m around any measurement location. Airborne observations revealed the dominant source of elevated urban particulate number and mass concentrations being local, i.e., not being caused by long-range transport. Surface-based observations related these two parameters predominantly to traffic sources. Vegetated areas lowered the pollutant concentrations substantially with ozone being reduced most by coniferous forests, which is most likely caused by their reactive biogenic VOC emissions. With respect to the overall potential to reduce air pollutant levels, forests were found to result in the largest decrease, followed by parks and facilities for sports and leisure. Surface temperature was generally 0.6–2.1 °C lower in vegetated regions, which in turn will have an impact on tropospheric chemical processes. Based on our findings, effective future mitigation activities to provide a more sustainable and healthier urban environment should focus predominantly on reducing fossil-fuel emissions from traffic as well as on increasing vegetated areas

    A modified atmospheric non-hydrostatic model on low aspect ratio grids

    Get PDF
    © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Tellus A 64 (2012): 17516, doi:10.3402/tellusa.v64i0.17516.It is popular to use a horizontal explicit and a vertical implicit (HE-VI) scheme in the compressible nonhydrostatic (NH) model. However, when the aspect ratio becomes small, a small time-interval is required in HE-VI, because the Courant-Fredrich-Lewy (CFL) criterion is determined by the horizontal grid spacing. Furthermore, simulations from HE-VI can depart from the forward–backward (FB) scheme in NH even when the time interval is less than the CFL criterion allowed. Hence, a modified non-hydrostatic (MNH) model is proposed, in which the left-hand side of the continuity equation is multiplied by a parameter d (45d516, in this study). When the linearized MNH is solved by FB (can be other schemes), the eigenvalue shows that MNH can suppress the frequency of acoustic waves very effectively but does not have a significant impact on the gravity waves. Hence, MNH enables to use a longer time step than that allowed in the original NH. When the aspect ratio is small, MNH solved by FB can be more accurate and efficient than the NH solved by HE-VI. Therefore, MNH can be very useful to study cloud, Large Eddy Simulation (LES), turbulence, flow over complex terrains, etc., which require fine resolution in both horizontal and vertical directions

    Experiential learning and the acquisition of managerial tacit knowledge

    Get PDF
    Tacit knowledge is believed to be one factor that distinguishes successful managers from others. We sought to determine whether levels of accumulated managerial tacit knowledge (LAMTK) were associated with managers' dominant learning styles. Instruments used in the study, involving 356 Malaysian public sector employees, included Sternberg et al.'s (2000) Tacit Knowledge Inventory for Managers and a normative version of Kolb's (1999a) Learning Styles Inventory (LSI-Ill). Findings suggest that LAMTK is independent of the length of subjects' general work experience, but positively related to the amount of time spent working in a management context. Learning styles also had a significant relationship. Subjects who spent most of their time performing management functions and whose dominant learning styles were accommodating had significantly higher LAMTK than those with different learning styles. We also found support for the belief that learners with a strong preference for all four different abilities defined in Kolb's learning theory may be critical for effective experiential learning

    The influence of learning styles on knowledge acquisition in public sector management

    Get PDF
    This research note outlines a project designed to investigate the role of training institutions in providing effective training and development programmes for managers. The investigation is being carried out in the light of recent criticisms levelled against the nature of formal learning environments prevalent in most institutional settings. The traditional role of trainers and developers as the providers of knowledge and skills for the development of competent managers runs contrary to recent findings, which suggest that managers learn more effectively in informal settings, rather than the formal settings evident in many development programmes. The idea that explicitly extracted competencies are the target every manager should aim for to improve their effectiveness is also challenged because competencies alone are no longer regarded as a sufficient criterion for success. Recent research has attached greater importance to the need for helping managers to see knowledge as a social phenomenon, and one factor that might distinguish successful managers from others is tacit knowledge (Wagner & Sternberg, 1987; Argyris, 1999). A major focus of this study is to explore the possibility that the level and content of tacit knowledge acquired by managers may be influenced by their individual learning styles, and the degree to which their dominant styles are matched with the context of their work environment

    BAERLIN2014-stationary measurements and source apportionment at an urban background station in Berlin, Germany

    Get PDF
    The "Berlin Air quality and Ecosystem Research: Local and long-range Impact of anthropogenic and Natural hydrocarbons" (BAERLIN2014) campaign was conducted during the 3 summer months (June-August) of 2014. During this measurement campaign, both stationary and mobile measurements were undertaken to address complementary aims. This paper provides an overview of the stationary measurements and results that were focused on characterization of gaseous and particulate pollution, including source attribution, in the Berlin-Potsdam area, and quantification of the role of natural sources in determining levels of ozone and related gaseous pollutants. Results show that biogenic contributions to ozone and particulate matter are substantial. One indicator for ozone formation, the OH reactivity, showed a 31% (0.82 +/- 0.44 s(-1) and 75% (3.7 +/- 0.90 s(-1) contribution from biogenic non-methane volatile organic com-pounds (NMVOCs) for urban background (2.6 +/- 0.68 s(-1) and urban park (4.9 +/- 1.0 s(-1) location, respectively, emphasizing the importance of such locations as sources of biogenic NMVOCs in urban areas. A comparison to NMVOC measurements made in Berlin approximately 20 years earlier generally show lower levels today for anthropogenic NMVOCs. A substantial contribution of secondary organic and inorganic aerosol to PM10 concentrations was quantified. In addition to secondary aerosols, source apportionment analysis of the organic carbon fraction identified the contribution of biogenic (plant-based) particulate matter, as well as primary contributions from vehicles, with a larger contribution from diesel compared to gasoline vehicles, as well as a relatively small contribution from wood burning, linked to measured levoglucosan

    DCMIP2016: the splitting supercell test case

    Get PDF
    This paper describes the splitting supercell idealized test case used in the 2016 Dynamical Core Model Intercomparison Project (DCMIP2016). These storms are useful test beds for global atmospheric models because the horizontal scale of convective plumes is O(1&thinsp;km), emphasizing non-hydrostatic dynamics. The test case simulates a supercell on a reduced-radius sphere with nominal resolutions ranging from 4 to 0.5&thinsp;km and is based on the work of Klemp et al. (2015). Models are initialized with an atmospheric environment conducive to supercell formation and forced with a small thermal perturbation. A simplified Kessler microphysics scheme is coupled to the dynamical core to represent moist processes. Reference solutions for DCMIP2016 models are presented. Storm evolution is broadly similar between models, although differences in the final solution exist. These differences are hypothesized to result from different numerical discretizations, physics–dynamics coupling, and numerical diffusion. Intramodel solutions generally converge as models approach 0.5&thinsp;km resolution, although exploratory simulations at 0.25&thinsp;km imply some dynamical cores require more refinement to fully converge. These results can be used as a reference for future dynamical core evaluation, particularly with the development of non-hydrostatic global models intended to be used in convective-permitting regimes.</p
    • 

    corecore