68 research outputs found

    Numerical simulation of an air-supported structure in the air flow

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    Wind load is often the critical load for air-supported structures. For example, high wind demolished an air-supported tennis court roof in Zhulebino district of Moscow on May 29, 2017. Aerodynamic instability (buffeting, flutter, etc.) can produce excessive slack regions and extremely large deflections. That is why the coupled analysis should be carried out to understanding aeroelastic behavior of air-supported structures under wind loads. The technique of the nonlinear numerical analysis of air-supported structures including fluidstructural interaction (FSI) has been described in the present paper. Numerical simulation of the tunnel test of large-scale air-supported model has been carried out as an example of using this technique. Wind tunnel study is described in the papers1, 2. Experimental deformed shape, pressure coefficients and aerodynamic forces were compared with the results of presented numerical simulation. Computations were carried out with using of commercial code ANSYS 15.0. Some difficulties appeared during simulation process are discussed. An applicability of the proposed technique to the considered problem was confirmed by a good agreement of the experimental and numerical results. Both methods showed that surface wind loads can increase due to deformation of a structure. These conclusions emphasize the importance of researches on wind interaction with air-supported structures

    CD4 T Cells Treated with gp120 Acquire a CD45R0+/CD45RA+ Phenotype

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    HIV-infected patients exhibit quantitative and qualitative defects in CD4 T cells, including having increased numbers of CD4+CD45R0+/CD45RA+ T cells, although it remains unclear how these cells arise. Here we demonstrate that gp120 treatment of activated but not resting primary human CD4 T cells decreases number of cells with single positive CD45R0+/CD45RA- effector memory phenotype while proportionally increasing the subset of cells with double positive CD45R0+/CD45RA+ mixed phenotype. We found that double positive CD45R0+/CD45RA+CD4 T cells preferentially undergo apoptosis while single positive CD45R0+/CD45RA- and CD45R0-/CD45RA+ do not. Blocking gp120-CD4 interaction with sCD4 or inhibition Lck activity reverses gp120 induced increase in double positive CD45R0+/CD45RA+CD4 T cells and subsequently diminishes the apoptosis of double positive CD45R0+/CD45RA+ cells. Altogether these data indicate that gp120 ligation of the CD4 receptor increases the number of double positive CD45R0+/CD45RA+ CD4 T cells which subsequently undergo apoptosis in a CD4 dependent manner

    Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

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    Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival

    Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models

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    Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders

    All-optical spatio-temporal control of electron emission from SiO2 nanospheres with femtosecond two-color laser fields

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    Field localization by nanostructures illuminated with laser pulses of well-defined waveform enables spatio-temporal tailoring of the near-fields for sub-cycle control of electron dynamics at the nanoscale. Here, we apply intense linearly-polarized two-color laser pulses for all-optical control of the highest energy electron emission from SiO2 nanoparticles. For the size regime where light propagation effects become important, we demonstrate the possibility to control the preferential emission angle of a considerable fraction of the fastest electrons by varying the relative phase of the two-color field. Trajectory based semi-classical simulations show that for the investigated nanoparticle size range the directional steering can be attributed to the two-color effect on the electron trajectories, while the accompanied modification of the spatial distribution of the ionization rate on the nanoparticle surface has only a minor effect.11Ysciescopu
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