328 research outputs found
Mission design for LISA Pathfinder
Here we describe the mission design for SMART-2/LISA Pathfinder. The best
trade-off between the requirements of a low-disturbance environment and
communications distance is found to be a free-insertion Lissajous orbit around
the first co-linear Lagrange point of the Sun-Earth system L1, 1.5x 10^6 km
from Earth. In order to transfer SMART-2/LISA Pathfinder from a low Earth
orbit, where it will be placed by a small launcher, the spacecraft carries out
a number of apogee-raise manoeuvres, which ultimatively place it to a parabolic
escape trajectory towards L1. The challenges of the design of a small mission
are met, fulfilling the very demanding technology demonstration requirements
without creating excessive requirements on the launch system or the ground
segment.Comment: 7 pages, 6 figures, 5th International LISA Symposium, see
http://www.landisoft.de/Markus-Landgra
Grow More Rape
Rape, rape, rape and more rape—that should be an important part of the crop program on Iowa farms that carry livestock, particularly swine, sheep and calves
Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro
Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices
Platelet FcγRIIA-induced serotonin release exacerbates the severity of Transfusion-Related Acute Lung Injury in mice
Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. The mechanism of human antibody-mediated TRALI, especially the involvement of the Fcγ receptors, is not clearly established. Contrary to mice, human platelets are unique in their expression of the FcγRIIA/CD32A receptor, suggesting that our understanding of the pathogenesis of antibody-mediated TRALI is partial, as the current murine models incompletely recapitulate the human immunology. We evaluated the role of FcγRIIA/CD32A in TRALI using a humanized mouse model expressing the FcγRIIA/CD32A receptor. When challenged with a recombinant chimeric human immunoglobulin G1/mouse anti–major histocompatibility complex class I monoclonal antibody, these mice exhibited exacerbated alveolar edema and higher mortality compared with wild-type (WT) mice. Unlike in WT mice, monocytes/macrophages in CD32A(+) mice were accessory for TRALI initiation, indicating the decisive contribution of another cell type. Platelet activation was dramatically increased in CD32A(+) animals, resulting in their increased consumption and massive release of their granule contents. Platelet depletion prevented the exacerbation of TRALI in CD32A(+) mice but did not affect TRALI in WT animals. By blocking platelet serotonin uptake with fluoxetine, we showed that the severity of TRALI in CD32A(+) mice resulted from the serotonin released by the activated platelets. Furthermore, inhibition of 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate, before or after the induction of TRALI, abolished the aggravation of lung edema in CD32A(+) mice. Our findings show that platelet FcγRIIA/CD32A activation exacerbates antibody-mediated TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate TRALI in patients
β-Glucuronidase triggers extracellular MMAE release from an integrin-targeted conjugate
A non-internalizing \u3b1v\u3b23 integrin ligand was conjugated to the anticancer drug MMAE through a \u3b2-glucuronidase-responsive linker. In the presence of \u3b2-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics
A Role of the Fast ATP-gated P2X1 Cation Channel in Thrombosis of Small Arteries In Vivo
The P2X1 receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools. In this paper, we have used P2X1−/− and wild-type mouse platelets, treated with apyrase to prevent desensitization, to demonstrate the function of P2X1 in the response to thrombogenic stimuli. In vitro, the collagen-induced aggregation and secretion of P2X1-deficient platelets was decreased, as was adhesion and thrombus growth on a collagen-coated surface, particularly when the wall shear rate was elevated. In vivo, the functional role of P2X1 could be demonstrated using two models of platelet-dependent thrombotic occlusion of small arteries, in which blood flow is characterized by a high shear rate. The mortality of P2X1−/− mice in a model of systemic thromboembolism was reduced and the size of mural thrombi formed after a laser-induced vessel wall injury was decreased as compared with normal mice, whereas the time for complete thrombus removal was shortened. Overall, the P2X1 receptor appears to contribute to the formation of platelet thrombi, particularly in arteries in which shear forces are high
Design of floor structures for human induced vibrations
In recent years, the introduction of new structural materials and innovative construction processes, associated to architectural and space arrangement requirements, in multi-storey buildings construction have produced significantly more flexible floor structural systems. The design of these floor systems is usually controlled by serviceability criteria, deflections or vibrations. Recognizing a gap in the design codes, this report gives a procedure for the determination and assessment of floor response for human induced vibrations.
First, the proposed procedure is presented, giving particular attention to the human induced loading characterization, dynamic properties and the comfort criteria for the verification of floor structural systems. Design charts are derived. Finally, it is presented a guidance manual to use the simplified procedure proposed for the design of building floors for human induced vibrations. Two worked examples of the proposed design procedure are given, namely a filigree slab with ACB-composite beams and a composite slab with steel beams.JRC.DG.G.5-European laboratory for structural assessmen
Wave vector dependence of the dynamics in supercooled metallic liquids
We present a detailed investigation of the wave vector dependence of
collective atomic motion in Au49Cu26.9Si16.3Ag5.5Pd2.3 and Pd42.5Cu27Ni9.5P21
supercooled liquids close to the glass transition temperature. Using x-ray
photon correlation spectroscopy in a precedent uncovered spatial range of only
few interatomic distances, we show that the microscopic structural relaxation
process follows in phase the structure with a marked slowing down at the main
average inter-particle distance. This behavior is accompanied by dramatic
changes in the shape of the intermediate scattering functions which suggest the
presence of large dynamical heterogeneities at length-scales corresponding to
few particle diameters. A ballistic-like mechanism of particle motion seems to
govern the structural relaxation of the two systems in the highly viscous
phase, likely associated to hopping of caged particles in agreement with
theoretical studies
Cooperation between NMDA-Type Glutamate and P2 Receptors for Neuroprotection during Stroke: Combining Astrocyte and Neuronal Protection
Excitotoxicity is the principle mechanism of acute injury during stroke. It is defined as the unregulated accumulation of excitatory neurotransmitters such as glutamate within the extracellular space, leading to over-activation of receptors, ionic disruption, cell swelling, cytotoxic Ca2+ elevation and a feed-forward loop where membrane depolarisation evokes further neurotransmitter release. Glutamate-mediated excitotoxicity is well documented in neurons and oligodendrocytes but drugs targeting glutamate excitotoxicity have failed clinically which may be due to their inability to protect astrocytes. Astrocytes make up ~50% of the brain volume and express high levels of P2 adenosine triphosphate (ATP)-receptors which have excitotoxic potential, suggesting that glutamate and ATP may mediate parallel excitotoxic cascades in neurons and astrocytes, respectively. Mono-cultures of astrocytes expressed an array of P2X and P2Y receptors can produce large rises in [Ca2+]i; mono-cultured neurons showed lower levels of functional P2 receptors. Using high-density 1:1 neuron:astrocyte co-cultures, ischemia (modelled as oxygen-glucose deprivation: OGD) evoked a rise in extracellular ATP, while P2 blockers were highly protective of both cell types. GluR blockers were only protective of neurons. Neither astrocyte nor neuronal mono-cultures showed significant ATP release during OGD, showing that cell type interactions are required for ischemic release. P2 blockers were also protective in normal-density co-cultures, while low doses of combined P2/GluR blockers where highly protective. These results highlight the potential of combined P2/GluR block for protection of neurons and glia.</jats:p
Household income determines access to specialized pediatric chronic pain treatment in Germany
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