679 research outputs found

    Shockwaves in converging geometries

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    Plate impact experiments are a powerful tool in equation of state (EOS) development, but are inherently limited by the range of impact velocities accessible to the gun. In an effort to dramatically increase the range of pressures which can be studied with available impact velocities, a new experimental technique is being developed. The possibility of using a confined converging target to focus Shockwaves and produce a large amplitude pressure pulse is examined. When the planar shock resulting from impact enters the converging target the impedance mismatch at the boundary of the confinement produces reflected Mach waves and the subsequent wave interactions produce a diffraction cycle resulting in increases in the shock strength with each cycle. Since this configuration is limited to relatively low impedance targets, a second technique is proposed in which the target is two concentric cylinders designed such that the inner cylinder will have a lower shock velocity than the much larger shock velocity in the outer cylinder. The resulting dispersion in the wave front creates converging shocks, which will interact and eventually result in a steady Mach configuration with an increase in pressure in the Mach disk. Numerical simulations indicate a significant increase in pressure for both methods and show promise for the proposed concepts

    Advances in Shock Compression of Mantle Materials and Implications

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    Hugoniots of lower mantle mineral compositions are sensitive to the conditions where they cross phase boundaries including both polymorphic phase transitions and partial to complete melting. For SiO_2, the Hugoniot of fused silica passes from stishovite to partial melt (73 GPa, 4600 K) whereas the Hugoniot of crystal quartz passes from CaCi_2 structure to partial melt (116 GPa, 4900 K). For Mg_2SiO_4, the forsterite Hugoniot passes from the periclase +MgSiO_3 (perovskite) assemblage to melt before 152 GPa and 4300 K, whereas the wadsleyite Hugoniot transforms first to periclase +MgSiO_3 (post-perovskite) and then melts at 151 GPa and 4160 K. Shock states achieved from crystal enstatite are molten above 160 GPa. High-pressure Grüneisen parameters for molten states of MgSiO_3 and Mg_2SiO_4 increase markedly with compression, going from 0.5 to 1.6 over the 0 to 135 GPa range. This gives rise to a very large (>2000 K) isentropic rise in temperature with depth in thermal models of a primordial deep magma ocean within the Earth. These magma ocean isentropes lead to models that have crystallization initiating at mid-lower mantle depths. Such models are consistent with the suggestion that the present ultra-low velocity zones, at the base of the lowermost mantle, represent a dynamically stable, partially molten remnant of the primordial magma ocean. The new shock melting data for silicates support a model of the primordial magma ocean that is concordant with the Berkeley-Caltech iron core model [1] for the temperature at the center of the Earth

    Shock temperatures of preheated MgO

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    Shock temperature measurements via optical pyrometry are being conducted on single-crystal MgO preheated before compression to 1905–1924 K. Planar shocks were generated by impacting hot Mo(driver plate)-MgO targets with Mo or Ta flyers launched by the Caltech two-stage light-gas gun up to 6.6 km/s. Quasi-brightness temperature was measured with 2–3% uncertainty by a 6-channel optical pyrometer with 3 ns time resolution, over 500–900 nm spectral range. A high-power, coiled irradiance standard lamp was adopted for spectral radiance calibration accurate to 5%. In our experiments, shock pressure in MgO ranged from 102 to 203 GPa and the corresponding temperature varied from 3.78 to 6.53 kK. For the same particle velocity, preheated MgO Hugoniot has about 3% lower shock velocity than the room temperature Hugoniot. Although model shock temperatures calculated for the solid phase exceeded our measurements by ~5 times the uncertainty, there was no clear evidence of MgO melting, up to the highest compression achieved

    BDNF stimulation of protein synthesis in cortical neurons requires the map kinase-interacting kinase MNK1

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    Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here, we explore the involvement of the MNKs in brain-derived neurotrophic factor (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a combination of pharmacological and genetic approaches, we show that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E. Translation initiation is mediated by the interaction of eIF4E with the m7GTP cap of mRNA and with eIF4G. The latter interaction is inhibited by the interactions of eIF4E with partner proteins, such as CYFIP1, which acts as a translational repressor. We find that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on MNK1. Finally, using a novel combination of BONCAT and SILAC, we identify a subset of proteins whose synthesis is upregulated by BDNF signaling via MNK1 in neurons. Interestingly, this subset of MNK1-sensitive proteins is enriched for functions involved in neurotransmission and synaptic plasticity. Additionally, we find significant overlap between our subset of proteins whose synthesis is regulated by MNK1 and those encoded by known FMRP-binding mRNAs. Together, our data implicate MNK1 as a key component of BDNF-mediated translational regulation in neurons

    EXPERIMENTAL STUDIES OF MITIGATION MATERIALS FOR BLAST INDUCED TBI

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    The objective of this experimental study is to compare the effects of various materials obstructing the flow of a blast wave and the ability of the given material to reduce the damage caused by the blast. Several methods of energy transfer in blast wave flows are known or expected including: material interfaces with impedance mismatches, density changes in a given material, internal shearing, and particle fracture. The theory applied to this research is that the greatest energy transfer within the obstructing material will yield the greatest mitigation effects to the blast. Sample configurations of foam were varied to introduce material interfaces and filler materials with varying densities and impedances (liquids and powders). The samples were loaded according to a small scale blast produced by an explosive driven shock tube housing gram-range charges. The transmitted blast profiles were analyzed for variations in impulse characteristics and frequency components as compared to standard free field profiles. The results showed a rounding effect of the transmitted blast profile for all samples with the effects of the low density fillers surpassing all others tested.United States. Office of Naval Research (N00014-08-1-0261

    Quantitative non-canonical amino acid tagging based proteomics identifies distinct patterns of protein synthesis rapidly induced by hypertrophic agents in cardiomyocytes, revealing new aspects of metabolic remodeling

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    Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. Pathological myocardial growth is a risk factor for cardiac failure to which faster protein synthesis is a major driving element. We aimed to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are due to alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other non-dividing primary cells. To address this, an optimized QuaNCAT LC/MS method was used to selectively quantify newly synthesized proteins in such cells. The study showed both classical (phenylephrine; PE) and more recent (insulin) pathological cardiac hypertrophic agents increased the synthesis of proteins involved in glycolysis, the Krebs cycle / beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was upregulated by signaling through mTORC1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was upregulated in rat hearts following TAC. This isoform possesses specific regulatory properties that may be involved in metabolic remodeling and as a novel candidate biomarker. Levels of translation factor eEF1 also increased during TAC, likely contributing to faster cell mass accumulation. Interestingly, PKM2 and eEF1 were not up-regulated in pregnancy or exercise induced CH, suggesting them as pathological CH specific markers. The study methods may be of utility to the examination of protein synthesis in primary cells

    Dynamics of Elongation Factor 2 Kinase Regulation in Cortical Neurons in Response to Synaptic Activity

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    The rapid regulation of cell signaling in response to calcium in neurons is essential for real-time processing of large amounts of information in the brain. A vital regulatory component, and one of the most energy-intensive biochemical processes in cells, is the elongation phase of mRNA translation, which is controlled by the Ca(2+)/CaM-dependent elongation factor 2 kinase (eEF2K). However, little is known about the dynamics of eEF2K regulation in neurons despite its established role in learning and synaptic plasticity. To explore eEF2K dynamics in depth, we stimulated synaptic activity in mouse primary cortical neurons. We find that synaptic activity results in a rapid, but transient, increase in eEF2K activity that is regulated by a combination of AMPA and NMDA-type glutamate receptors and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) pathways. We then used computational modeling to test the hypothesis that considering Ca(2+)-coordinated MEK/ERK, mTORC1, and eEF2k activation is sufficient to describe the observed eEF2K dynamics. Although such a model could partially fit the empirical findings, it also suggested that a crucial positive regulator of eEF2K was also necessary. Through additional modeling and empirical evidence, we demonstrate that AMP kinase (AMPK) is also an important regulator of synaptic activity-driven eEF2K dynamics in neurons. Our combined modeling and experimental findings provide the first evidence that it is necessary to consider the combined interactions of Ca(2+) with MEK/ERK, mTORC1, and AMPK to adequately explain eEF2K regulation in neurons
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