Harmonic Generation and Inverse Cascade in the z-Pinch Driven, Preseeded Multimode, Magneto-Rayleigh-Taylor Instability.

The magneto-Rayleigh-Taylor instability (MRTI) plays an essential role in astrophysical systems and in magneto-inertial fusion, where it is known to be an important degradation mechanism of confinement and target performance. In this Letter, we show for the first time experimental evidence of mode mixing and the onset of an inverse-cascade process resulting from the nonlinear coupling of two discrete preseeded axial modes (400- and 550-µm wavelengths) on an Al liner that is magnetically imploded using the 20-MA, 100-ns rise-time Z Machine at Sandia National Laboratories. Four radiographs captured the temporal evolution of the MRTI. We introduce a novel unfold technique to analyze the experimental radiographs and compare the results to simulations and to a weakly nonlinear model. We find good quantitative agreement with simulations using the radiation magnetohydrodynamics code hydra. Spectral analysis of the MRTI time evolution obtained from the simulations shows evidence of harmonic generation, mode coupling, and the onset of an inverse-cascade process. The experiments provide a benchmark for future work on the MRTI and motivate the development of new analytical theories to better understand this instability.

Experimental Demonstration of the Stabilizing Effect of Dielectric Coatings on Magnetically Accelerated Imploding Metallic Liners.

Enhanced implosion stability has been experimentally demonstrated for magnetically accelerated liners that are coated with 70 µm of dielectric. The dielectric tamps liner-mass redistribution from electrothermal instabilities and also buffers coupling of the drive magnetic field to the magneto-Rayleigh-Taylor instability. A dielectric-coated and axially premagnetized beryllium liner was radiographed at a convergence ratio [CR=Rin,0/Rin(z,t)] of 20, which is the highest CR ever directly observed for a strengthless magnetically driven liner. The inner-wall radius Rin(z,t) displayed unprecedented uniformity, varying from 95 to 130 µm over the 4.0 mm axial height captured by the radiograph.

Magnetic field measurements via visible spectroscopy on the Z machine.

Sandia's Z Machine uses its high current to magnetically implode targets relevant to inertial confinement fusion. Since target performance is highly dependent on the applied drive field, measuring magnetic field at the target is essential for accurate simulations. Recently, the magnetic field at the target was measured through splitting of the sodium 3s-3p doublet at 5890 and 5896 Å. Spectroscopic dopants were applied to the exterior of the target, and spectral lines were observed in absorption. Magnetic fields in excess of 200 T were measured, corresponding to drive currents of approximately 5 MA early in the pulse.

Observations of modified three-dimensional instability structure for imploding z-pinch liners that are premagnetized with an axial field.

Novel experimental data are reported that reveal helical instability formation on imploding z-pinch liners that are premagnetized with an axial field. Such instabilities differ dramatically from the mostly azimuthally symmetric instabilities that form on unmagnetized liners. The helical structure persists at nearly constant pitch as the liner implodes. This is surprising since, at the liner surface, the azimuthal drive field presumably dwarfs the axial field for all but the earliest stages of the experiment. These fundamentally 3D results provide a unique and challenging test for 3D-magnetohydrodynamics simulations.

Penetrating radiography of imploding and stagnating beryllium liners on the Z accelerator.

The implosions of initially solid beryllium liners (tubes) have been imaged with penetrating radiography through to stagnation. These novel radiographic data reveal a high degree of azimuthal correlation in the evolving magneto-Rayleigh-Taylor structure at times just prior to (and during) stagnation, providing stringent constraints on the simulation tools used by the broader high energy density physics and inertial confinement fusion communities. To emphasize this point, comparisons to 2D and 3D radiation magnetohydrodynamics simulations are also presented. Both agreement and substantial disagreement have been found, depending on how the liner's initial outer surface finish was modeled. The various models tested, and the physical implications of these models are discussed. These comparisons exemplify the importance of the experimental data obtained.

Measurements of magneto-Rayleigh-Taylor instability growth during the implosion of initially solid Al tubes driven by the 20-MA, 100-ns Z facility.

The first controlled experiments measuring the growth of the magneto-Rayleigh-Taylor instability in fast (∼100 ns) Z-pinch plasmas are reported. Sinusoidal perturbations on the surface of an initially solid Al tube (liner) with wavelengths of 25-400 µm were used to seed the instability. Radiographs with 15 µm resolution captured the evolution of the outer liner surface. Comparisons with numerical radiation magnetohydrodynamic simulations show remarkably good agreement down to 50 µm wavelengths.

Radiating shock measurements in the Z-pinch dynamic hohlraum.

The Z-pinch dynamic hohlraum is an x-ray source for high energy-density physics studies that is heated by a radiating shock to radiation temperatures >200 eV. The time-dependent 300-400 eV electron temperature and 15-35 mg/cc density of this shock have been measured for the first time using space-resolved Si tracer spectroscopy. The shock x-ray emission is inferred from these measurements to exceed 50 TW, delivering >180 kJ to the hohlraum.

Demonstration of radiation pulse shaping with nested-tungsten-wire-array pinches for high-yield inertial confinement fusion.

Nested wire-array pinches are shown to generate soft x-ray radiation pulse shapes required for three-shock isentropic compression and hot-spot ignition of high-yield inertial confinement fusion capsules. We demonstrate a reproducible and tunable foot pulse (first shock) produced by interaction of the outer and inner arrays. A first-step pulse (second shock) is produced by inner array collision with a central CH2 foam target. Stagnation of the inner array at the axis produces the third shock. Capsules optimized for several of these shapes produce 290-900 MJ fusion yields in 1D simulations.

Hot dense capsule-implosion cores produced by Z-pinch dynamic Hohlraum radiation.

Hot dense capsule implosions driven by Z-pinch x rays have been measured using a approximately 220 eV dynamic Hohlraum to implode 1.7-2.1 mm diameter gas-filled CH capsules. The capsules absorbed up to approximately 20 kJ of x rays. Argon tracer atom spectra were used to measure the T(e) approximately 1 keV electron temperature and the n(e) approximately 1-4 x 10(23) cm(-3) electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak emission values of T(e), n(e), and symmetry, indicating reasonable understanding of the Hohlraum and implosion physics.

X-ray imaging measurements of capsule implosions driven by a Z-pinch dynamic hohlraum.

The radiation and shock generated by impact of an annular tungsten Z-pinch plasma on a 10-mm diam 5-mg/cc CH(2) foam are diagnosed with x-ray imaging and power measurements. The radiative shock was virtually unaffected by Z-pinch plasma instabilities. The 5-ns-duration approximately 135-eV radiation field imploded a 2.1-mm-diam CH capsule. The measured radiation temperature, shock radius, and capsule radius agreed well with computer simulations, indicating understanding of the main features of a Z-pinch dynamic-hohlraum-driven capsule implosion.

SMRTe, a silencing mediator for retinoid and thyroid hormone receptors-extended isoform that is more related to the nuclear receptor corepressor.

SMRT (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor copressor) mediate transcriptional repression of important regulators that are involved in many signaling pathways. SMRT and N-CoR are related proteins that form complexes with mSin3A/B and histone deacetylases to induce local chromatin condensation and transcriptional repression. However, SMRT is substantially smaller than N-CoR, lacking an N-terminal domain of approximately 1,000 aa that are present in N-CoR. Here, we report the identification of SMRT-extended (SMRTe), which contains an N-terminal sequence that shows striking similarity with N-CoR. As in N-CoR, this SMRTe-N-terminal domain also represses basal transcription. We find that SMRTe expression is regulated during cell cycle progression and SMRTe transcripts are present in many embryonic tissues. These data redefine a structurally and functionally more related nuclear receptor corepressor family and suggest an additional role for SMRTe in the regulation of cycle-specific gene expression in diverse signaling pathways.

v-src activation of the collagenase-1 (matrix metalloproteinase-1) promoter through PEA3 and STAT: requirement of extracellular signal-regulated kinases and inhibition by retinoic acid receptors.

Collagenase-1 (matrix metalloproteinase-1 (MMP-1)) degrades the extracellular matrix and enhances the invasive phenotype of tumor cells. v-src activated MMP-1 transcription through a series of elements in the proximal promoter, including the E2BP (nt -172), polyoma virus enhancer A3 (PEA3) (nt -94), activator protein-1 (AP-1) (nt -72), and signal transducer and activator of transcription (STAT) (nt -57) consensus sites. Of these sites, PEA3 and STAT contributed specifically to induction by v-src, whereas the remaining elements were also involved in induction by the phorbol ester phorbol myristate acetate (PMA). However, in contrast to MMP-1 induction by PMA, an AP-1 site located at nt -186 did not contribute to v-src induction. These results suggest divergence of the tyrosine kinase- and protein kinase C-dependent pathways with respect to MMP-1 transcription. v-src induced MMP-1 through mitogen-activated protein kinases, with extracellular signal-regulated kinases playing a larger role than c-jun N-terminal kinase. Retinoic acid, which inhibits the progression of certain cancers, repressed v-src-induced MMP-1 transcription. Constitutive expression of retinoic acid receptors (RARs) alpha or beta, but not gamma, or of retinoid X receptor alpha, repressed v-src-induced collagenase-1 transcription. We concluded that oncogenic induction of MMP-1 by v-src depends on signaling pathways and cis-acting sequences that are distinct from those involved in phorbol ester activation. Furthermore, v-src induction of MMP-1 may, by acting in concert with other genes, enhance matrix degradation and tumor progression, and retinoic acid and RARs may antagonize this induction in an RAR type-specific manner.

The nuclear receptor corepressor SMRT inhibits interstitial collagenase (MMP-1) transcription through an HRE-independent mechanism.

Nuclear receptors inhibit synthesis of collagenase-1 (matrix metalloproteinase-1; MMP-1), an enzyme that degrades interstitial collagens and contributes to joint pathology in rheumatoid arthritis. SMRT (Silencing Mediator for Retinoid and Thyroid hormone receptors) mediates the repressive effect of nuclear receptors at hormone responsive elements (HREs), prompting us to investigate whether this co-repressor could also regulate transcription of MMP-1, which lacks any known HREs. We find that primary synovial fibroblasts express SMRT. When over-expressed by transient transfection, SMRT inhibits MMP-1 promoter activity induced by interleukin-1 (IL-1), phorbol phorbol myristate acetate (PMA) or v-Src. SMRT apparently inhibits MMP-1 gene expression by interfering with one or more transcriptional elements clustered in a region between -321 and +63. We conclude that SMRT negatively regulates MMP-1 synthesis through a novel, HRE-independent mechanism that involves proximal regions of the MMP-1 promoter.

Characterization of receptor interaction and transcriptional repression by the corepressor SMRT.

SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) are two related transcriptional corepressors that contain separable domains capable of interacting with unliganded nuclear receptors and repressing basal transcription. To decipher the mechanisms of receptor interaction and transcriptional repression by SMRT/N-CoR, we have characterized protein-protein interacting surfaces between SMRT and nuclear receptors and defined transcriptional repression domains of both SMRT and N-CoR. Deletional analysis reveals two individual nuclear receptor domains necessary for stable association with SMRT and a C-terminal helix essential for corepressor dissociation. Coordinately, two SMRT domains are found to interact independently with the receptors. Functional analysis reveals that SMRT contains two distinct repression domains, and the corresponding regions in N-CoR also repress basal transcription. Both repression domains in SMRT and N-CoR interact weakly with mSin3A, which in turn associates with a histone deacetylase HDAC1 in a mammalian two-hybrid assay. Far-Western analysis demonstrates a direct protein-protein interaction between two N-CoR repression domains with mSin3A. Finally we demonstrate that overexpression of full-length SMRT further represses basal transcription from natural promoters. Together, these results support a role of SMRT/N-CoR in corepression through the utilization of multiple mechanisms for receptor interactions and transcriptional repression.

Inhibition of rabbit collagenase (matrix metalloproteinase-1; MMP-1) transcription by retinoid receptors: evidence for binding of RARs/RXRs to the -77 AP-1 site through interactions with c-Jun.

Treatment of synovial fibroblasts with retinoic acid (RA) decreases their expression of collagenase (matrix metalloproteinase-1 or MMP-1), an enzyme that degrades interstitial collagens and contributes to the pathology of rheumatoid arthritis. This inhibition results, at least in part, from RA-induced decreases in the mRNA for the transactivators Fos and Jun (with concominant increases in RAR mRNA) and by sequestration of Fos/Jun by RARs/RXRs. Previously, we provided evidence that retinoid receptors are also present in complexes that bind to fragments of rabbit MMP-1 promoter DNA containing an AP-1 site at -77 (Pan et al., 1995, J. Cell. Biochem., 57:575-589). However, it was unclear whether RARs and retinoid X receptors (RXRs) were binding directly to the DNA or indirectly through another protein. We now use a sensitive MMP-1 promoter/luciferase reporter construct to confirm the transcriptional role of the AP-1 site at -77. In addition, with electrophoretic mobility shift analyses (EMSAs), antibody "supershifts" and DNAase 1 footprinting, we examine the interaction of retinoid receptors and AP-1 protein on the MMP-1 promoter. We demonstrate that RARs, RXRs, and c-Jun form a complex at the AP-1 site in which c-Jun binds directly to the DNA and apparently tethers the retinoid receptors to the complex. We conclude that retinoid receptors/AP-1 protein interactions at the DNA may provide an additional means of controlling collagenase gene transcription by retinoids.

Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms.

Agents like retinoids, thyroid hormone, glucocorticoids, progesterone, androgens, which bind to members of the nuclear receptor superfamily, inhibit the synthesis of matrix metalloproteinases (MMPs) in many cell types. These Zn2(+)- and Ca2(+)-dependent MMPs degrade components of the extracellular matrix (ECM), and precise regulation of their expression is crucial in many normal processes. However, inappropriate expression of MMPs contributes to a variety of invasive and erosive diseases, and inhibition of MMP synthesis provides an important mechanism for controlling such aberrant or dysregulated responses. Nuclear receptors control MMPs through a variety of seemingly redundant mechanisms. First, nuclear receptors act on the promoters of MMP genes to enhance or suppress trans-activation. Ironically, in a family of genes that exhibits substantial regulation by nuclear receptors, few consensus hormone responsive elements (HREs) have been deomonstrated in MMP promoters. Rather, inhibition of MMPs occurs primarily, but not exclusively, at AP-1 sites. Here, nuclear receptors form complexes on the DNA through interactions with AP-1 proteins, sequester Fos/Jun and/or decrease the mRNAs for these transcription factors. Second, nuclear receptors and their ligands can indirectly inhibit MMPs. For instance, both retinoids and glucocorticoids induce the transcription of TIMPs (tissue inhibitor of metalloproteinases), which complex with MMPs and inhibit enzymatic activity, and progesterone stimulates production of transforming growth factor-beta (TGF-beta), which in turn suppresses MMP-7 (matrilysin). Finally, nuclear receptors bind to coactivators, corepressors, and components of the general transcriptional apparatus, but the potential role of these interactions in MMP regulation remains to be determined. We conclude that nuclear receptors utilize multiple, apparently redundant, mechanisms to inhibit MMP gene expression, assuring precise control of ECM degradation under a variety of physiologic and pathologic conditions.

Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability.

Matrix metalloproteinase-1 (MMP-1) is one of three collagenases that can degrade the interstitial collagens, types I, II, and III at neutral pH. As these collagens are the most abundant proteins in the body, collagenase plays a critical role in modeling and remodeling the extracellular matrix. Therefore, it is not surprising that MMP-1 gene expression can be regulated at multiple points. Procollagenase can be activated by mechanisms that generate an active enzyme with differing specific activities, and the active enzyme can be inhibited by complexing with either the tissue inhibitor of metalloproteinases (TIMPs) or alpha 2 macroglobulin. The activator protein-1 (AP-1) site in the collagenase promoter plays a prominent role in the transcriptional control of the collagenase gene. It is essential for basal transcription, and contributes to induction by phorbol esters, although other sites in the proximal promoter are essential. In contrast, transactivation by cytokines such as Interleukin-1 depends on sequences in more distal regions of the promoter. Posttranscriptional mechanisms also regulate gene expression, and several cytokines and growth factors increase the stability of the collagenase transcript. Finally, glucocorticoid hormones repress transcription of the collagenase gene by the interaction of glucocorticoid receptors with the AP-1 proteins, Fos and Jun. Retinoids also suppress transcription by mechanisms that involve down-regulation of fos and jun mRNA, sequestration of Fos and Jun proteins, and the formation of complexes of retinoic acid receptors (RAR/RXR heterodimers) and AP-1 proteins on the DNA. These multiple points of regulation assure precise control of collagenolytic activity in a variety of physiologic and pathologic conditions.

Interaction of mouse thymocytes and a thymocyte-like cell line with the ECM glycoprotein entactin.

Entactin, a sulfated glycoprotein of 150-kDa, is a component of the extracellular matrix that promotes the adhesion of numerous types of cells, including lymphocytes (Li and Cheung, J. Immunol. 149, 3174, 1992), prompting us to question whether developing T lymphocytes in the thymus (thymocytes) also interact with this molecule. We thus investigated the adhesion of a thymocyte-like cell line (S49.1) to entactin, as well as the adhesion and migration of primary mouse thymocytes upon entactin-coated surfaces. In dose-response and time-course experiments, a 50 micrograms/mL coating concentration of entactin and a 60-min incubation period induced a high level (approximately 65-85%) of S49.1 cell adhesion. Preincubation of the S49.1 cells in medium containing the metabolic inhibitors sodium azide or 2-deoxy-D-glucose inhibited adhesion to entactin 47.2 and 79.5%, respectively. Furthermore, performing the adhesion assay at 4 degrees C instead of at 37 degrees C inhibited S49.1 cell adhesion 27.1%. A high percentage (approximately 90-100%) of S49.1 cells also bound to the lectin concanavalin A and to fibronectin, while laminin promoted only 19.3% adhesion. Our adhesion assay (St. John et al., J. Immunol. Methods, 170, 159, 1994) was then modified to permit a comparison of S49.1 cell adhesion strength to entactin relative to the other substrates. Consequently, Concanavalin A promoted the strongest adhesion, followed by fibronectin and then entactin. In addition, high percentages (92.5, 63, and 75.9%, respectively) of primary thymocytes from 4- to 5-week-old BALB/c mice adhered to entactin, Con A, and fibronectin, while much lower levels (7.6%) of adhesion to laminin were observed. Using a capillary tube random migration assay to measure haptokinesis, entactin-, concanavalin A-, and fibronectin-coated surfaces stimulated little migration, while laminin-coated surfaces enhanced thymocyte migration extensively. Since entactin promoted thymocyte adhesion but affected migration only marginally, we suggest that this molecule may play a role in thymocyte localization during T cell development.

An adhesion assay using minimal shear force to remove nonadherent cells.

A new 96-well microtiter plate based adhesion assay was developed to measure weak cell adhesion. This assay is distinct from other adhesion assays by the procedure in which the nonadherent cells are removed. In most conventional adhesion assays, nonadherent cells are removed by aspiration followed by repeated washes. However, the shear force generated by such washing also detaches weakly adherent cells. In the minimal shear force adhesion assay (MSFA) described here, the removal of nonadherent cells is carried out by applying a gentle shear force in a fluid environment. In this procedure, adherent cells are not subjected to harsh and variable washing forces and are not exposed to surface tension caused by the removal of washing fluid between successive washes. Using the lymphoid cell lines XC1.5/51 and MPC11, the number of adherent cells determined by this new adhesion assay is three times higher than the conventional adhesion assay. This MSFA assay is simple, consistent, and easy to perform. With modifications for applying a defined shear force, this assay can be adopted to compare cell adhesion strength to various substrata.