30 research outputs found
DEM element modelling of silent piling group installation for offshore wind turbine foundations
Offshore wind farms are now built in deeper water and bigger foundations are required to stabilise wind turbines of increasing sizes. Pile driving is the most widespread foundation installation method, but more stringent environmental regulations necessitate costly mitigation methods to reduce underwater noise emissions. The silent piling (push-in) concept presented in this work is composed of a cluster of four piles, progressively installed by successive jacking sequences. During one sequence, each pile is moved downward by 0.5m stroke, while the other piles are used as reaction. This paper presents the results of Discrete Element Method (DEM) of the installation process. This work identifies the main features of the push-in installation method, such as pile interaction, progressive plugging and loss of efficiency as a function of depth. It is shown that the cluster capacity can reach six times the weight of the tool necessary to silently install the piles
Silent piling for offshore jacket foundations in sand:DEM and centrifuge modelling
The race to decarbonise the economy has led to an exponential growth of offshore wind farm developments across the globe. While monopiles are the dominating installed foundations, jacket structures are expected to be more and more common, as wind farms extend to deeper waters [1] and innovative technologies are required to alleviate some important challenges. Firstly, straight shafted piles are not particularly efficient to sustain large tensile demand induced by the push-pull axial loading of the foundations. Secondly, stricter regulations on underwater noise make mitigation methods for pile driving more expensive and silent piling tech-niques could be used as an alternative [2]. Figure 1(a) describes a new screw pile foundation that meets those two challenges [3]. The foundation is installed by rotary jacking, which avoids any impact related noise. The pile is composed of a large upper shaft, that is designed to resist the lateral load applied by the jacket structure, and a smaller lower shaft which reduces the torque demand during installation. A helix is attached close to the pile tip, to provide an enhanced axial resistance and facilitates the installation of the pile [4]. The main challenge during the pile installation is the very low reaction force that may be available offshore at the pile head, which consists only of the pile self-weight and the installation tool. The aim of this work is to demonstrate that screw piles can be installed for offshore applications by rotary jacking at low reaction force, via (geotechnical centrifuge, [2]) and numerical (DEM, [5]) modellin
RIPK3-Dependent Recruitment of Low-Inflammatory Myeloid Cells Does Not Protect from Systemic Salmonella Infection
ABSTRACT Regulated macrophage death has emerged as an important mechanism to defend against intracellular pathogens. However, the importance and consequences of macrophage death during bacterial infection are poorly resolved. This is especially true for the recently described RIPK3-dependent lytic cell death, termed necroptosis. Salmonella enterica serovar Typhimurium is an intracellular pathogen that precisely regulates virulence expression within macrophages to evade and manipulate immune responses, which is a key factor in its ability to cause severe systemic infections. We combined genetic and pharmacological approaches to examine the importance of RIPK3 for S. Typhimurium-induced macrophage death using conditions that recapitulate bacterial gene expression during systemic infection in vivo. Our findings indicate that noninvasive S. Typhimurium does not naturally induce macrophage necroptosis but does so in the presence of pan-caspase inhibition. Moreover, our data suggest that RIPK3 induction (following caspase inhibition) does not impact host survival following S. Typhimurium infection, which differs from previous findings based on inert lipopolysaccharide (LPS) injections. Finally, although necroptosis is typically characterized as highly inflammatory, our data suggest that RIPK3 skews the peritoneal myeloid population away from an inflammatory profile to that of a classically noninflammatory profile. Collectively, these data improve our understanding of S. Typhimurium-macrophage interactions, highlight the possibility that purified bacterial components may not accurately recapitulate the complexity of host-pathogen interactions, and reveal a potential and unexpected role for RIPK3 in resolving inflammation. IMPORTANCE Macrophages employ multiple strategies to limit pathogen infection. For example, macrophages may undergo regulated cell death, including RIPK3-dependent necroptosis, as a means of combatting intracellular bacterial pathogens. However, bacteria have evolved mechanisms to evade or exploit immune responses. Salmonella is an intracellular pathogen that avoids and manipulates immune detection within macrophages. We examined the contribution of RIPK3 to Salmonella-induced macrophage death. Our findings indicate that noninvasive Salmonella does not naturally induce necroptosis, but it does so when caspases are inhibited. Moreover, RIPK3 induction (following caspase inhibition) does not impact host survival following Salmonella systemic infection. Finally, our data show that RIPK3 induction results in recruitment of low-inflammatory myeloid cells, which was unexpected, as necroptosis is typically described as highly inflammatory. Collectively, these data improve our understanding of pathogen-macrophage interactions, including outcomes of regulated cell death during infection in vivo, and reveal a potential new role for RIPK3 in resolving inflammation
The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/1/epi13461_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/2/epi13461.pd
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CACHD1 is an α2Ύ-like protein that modulates CaV3 voltage-gated calcium channel activity
The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the alpha2delta voltage-gated Ca2+ channel (VGCC) auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular, CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1 and these proteins were in close proximity at the cell surface consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, co-expression of human CACHD1 with CaV3.1, CaV3.2 and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, alpha2delta-1 had no effect on peak current density or maximal conductance in either CaV3.1, CaV3.2 or CaV3.3. Comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female E19 rats, CACHD1 overexpression increased CaV3-mediated action potential (AP) firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an alpha2delta-like protein that functionally modulates CaV3 voltage-gated calcium channel activity
Progetto del museo e riqualificazione urbana. Studi per un Museo del Mobile e dell'Arredamento a CantĂč.
Riflessione critica sul significato e il ruolo urbano del museo contemporaneo. Indagando la tradizione canturina dell'arredo di qualitĂ , gli autori riconoscono nel Museo un dispoisitivo funzionale a un nuovo sviluppo dell'artigianato mobiliero e della cultura degli interni abitati. Sono anche illustrati i progetti per un Museo del Mobile e dell'Arredamento a CantĂč elaborati alla FacoltĂ di Architettura Civile del Politecnico di Milano
The VST telescope primary mirror safety system: simulation model and mechanical implementation
The VST telescope is a wide field survey telescope being installed at Cerro Paranal, Chile). Due to the geological nature of the area, telescopes in Chile are always submitted to unpredictable and sometimes severe earthquake conditions. In order to clarify some aspects of VST telescope seismic behavior not well represented by linear procedures like Response Spectrum Analysis, a transient nonlinear analysis of the whole telescope has been foreseen. A mixed approach Finite Element - Matlab-Simulink has been introduced and a linear FE model of the telescope has been developed, with all nonlinear devices sources modelled as linear elements. The FE model has been exported to Simulink, using a space state representation. In Simulink all nonlinearities are appropriately modeled and a base excitement corresponding to accelerograms compliant with Paranal MLE response spectrum is applied. Resulting force-time histories are then applied to a detailed finite element model of mirror, to compute stress field. The paper describes both Simulink and mirror FE analysis, giving also an overview of the actual safety system mechanical implementation, based on analysis results