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During the past decade, a number of diagnostic instruments have been developed that utilize electron pulse-dilation to achieve temporal resolution in the 5–30 ps range. These development efforts were motivated by the need for advanced diagnostics for high-energy density physics experiments around the world. The new instruments include single- and multi-frame gated imagers and non-imaging detectors that record continuous data streams. Electron pulse-dilation provides high-speed detection capability by converting incoming signals into a free electron cloud and manipulating the electron signal with electric and magnetic fields. Here, we discuss design details and applications of these instruments along with issues and challenges associated with employing the electron pulse-dilation technique. Additionally, methods to characterize instrument performance and improve tolerance to gamma and neutron background radiation are discussed. [ABSTRACT FROM AUTHOR]

The hydrodynamic instability growth of a reshocked single-mode interface between high energy density fluids is studied. A laser-driven shock wave is used to drive an initially solid, sinusoidal interface between a dense plastic (1.43 g/cc) and a light foam (≈ 0.110 g/cc). After the interface has grown to a nonlinear state where the amplitude is of order of the wavelength, it is reshocked. The reshock compresses the nonlinear perturbation, which then grows at about twice the rate. While the pre-reshock growth rate is sensitive to the initial amplitude and wavelength of the perturbation, the post-reshock growth rate is comparatively insensitive to the initial condition. Qualitatively, we observe that the perturbations are less coherent after reshock, consistent with the idea that having a reshock accelerates the transition to turbulence. We find that some memory of the initial condition remains, even after reshock at late time: it appears if the initial perturbations have large enough wavelengths, and the flow structure of size comparable to the initial wavelength persists through reshock. Our results agree with design simulations and are consistent with the phenomenology of reshock studies in conventional gaseous shock tubes. [ABSTRACT FROM AUTHOR]

Introduction: Translating basic science research into a safe and effective therapy for spinal cord injury (SCI) requires suitable large animal models for testing both implantable devices and biologic approaches to better approximate human anatomy and function. Hemisection lesions, routinely used for investigational purposes in small animals, are less frequently described in large animals that might be appropriate for translational studies. Size constraints of small animals (mice and rats) limits the predictability of the findings when scaled up. Our goal is to review the status of hemisection SCI in large animals across species and time to prepare for the testing of a novel intradural spinal cord stimulation device for control of spasticity in an ovine model. Methods and Results: We surveyed the literature on hemisection in quadrupeds and nonhuman primates, and catalogued the species, protocols and outcomes of the experimental work in this field. Feline, lapine, canine, simian, porcine, ovine and bovine models were the primary focal points. There is a consistent body of literature reporting use of the hemisection approach in large animals, but with differences in surgical technique depending on the goals and nature of the individual studies. While the injuries are not always consistent, the experimental variability is generally lower than that of the contusion-based approach. In general, as the body size of the animal increases, animal care requirements and the associated costs follow. In most cases, this is inversely correlated with the number of animals used in hemisection models. Conclusions: The hemisection approach to modeling SCI is straightforward compared with other methods such as the contusive impact and enables the transection of isolated ascending and descending tracts and segment specific cell bodies. This has certain advantages in models investigating post-injury axonal regrowth. However, this approach is not generally in line with the patho-physiologies encountered in SCI patients. Even so, the ability to achieve more control over the level of injury makes it a useful adjunct to contusive and ischemic approaches, and suggests a useful role in future translational studies. [ABSTRACT FROM AUTHOR]

A new experimental platform has been developed at the National Ignition Facility (NIF) for studying the Rayleigh-Taylor (RT) and Richtmyer-Meshkov (RM) instabilities in a planar geometry at high-energy-densities. The platform uses 60 beams of the NIF laser to drive an initially solid shock tube containing a pre-machined interface between dense and light materials. The strong shock turns the initially solid target into a plasma and the material boundary into a fluid interface with the imprinted initial condition. The interface evolves by action of the RT and RM instabilities and the growth is imaged with backlit x-ray radiography. We present our first data involving sinusoidal interface perturbations driven from the heavy side to the light side. Late-time radiographic images show the initial conditions reaching the deeply nonlinear regime and an evolution of fine structure consistent with a transition to turbulence. We show preliminary comparisons with post-shot numerical simulations and discuss the implications for future campaigns. [ABSTRACT FROM AUTHOR]

The performance of Inertial Confinement Fusion targets relies on the symmetric implosion of highly compressed fuel. X-ray area-backlit imaging is used to assess in-flight low mode 2D asymmetries of the shell. These time-resolved images of the shell exhibit features that can be related to the lift-off position of the membranes used to hold the capsule within the hohlraum. Here, we describe a systematic study of this membrane or "tent" thickness and its impact on the measured low modes for in-flight and self-emission images. The low mode amplitudes of the shell in-flight shape (P2 and P4) are weakly affected by the tent feature in time-resolved, backlit data. By contrast, time integrated self-emission images along the same axis exhibit a reversal in perceived P4 mode due to growth of a feature seeded by the tent, which can explain prior inconsistencies between the in-flight P4 and core P4, leading to a reevaluation of optimum hohlraum length. Simulations with a tent-like feature normalized to match the feature seen in the backlit images predict a very large impact on the capsule performance from the tent feature. [ABSTRACT FROM AUTHOR]

The DIlation X-ray Imager (DIXI) is a new, high-speed x-ray framing camera at the National Ignition Facility (NIF) sensitive to x-rays in the range of ≈2-17 keV. DIXI uses the pulse-dilation technique to achieve a temporal resolution of less than 10 ps, a ≈10x improvement over conventional framing cameras currently employed on the NIF (≈100 ps resolution), and otherwise only attainable with 1D streaked imaging. The pulse-dilation technique utilizes a voltage ramp to impart a velocity gradient on the signal-bearing electrons. The temporal response, spatial resolution, and x-ray sensitivity of DIXI are characterized with a short x-ray impulse generated using the COMET laser facility at Lawrence Livermore National Laboratory. At the NIF a pinhole array at 10 cm from target chamber center (tcc) projects images onto the photocathode situated outside the NIF chamber wall with a magnification of ≈64x. DIXI will provide important capabilities for warm-dense-matter physics, high-energy-density science, and inertial confinement fusion, adding important capabilities to temporally resolve hot-spot formation, x-ray emission, fuel motion, and mix levels in the hot-spot at neutron yields of up to 1017. We present characterization data as well as first results on electron-transport phenomena in buried-layer foil experiments. [ABSTRACT FROM AUTHOR]

Background: Thrombectomy devices are increasingly used for intra-arterial recanalization therapy in stroke. We analyzed whether the use of these devices modified the outcome of patients with acute basilar occlusion (BAO) at our institution. Methods: Between 1998 and 2012, one hundred forty-seven consecutive patients with acute BAO received recanalization therapy. In July 2009, for the first time, a thrombectomy device was used and hence the cohort was split into two chronological groups: BAO-1 (before July 2009) and BAO-2 (after July 2009). All patients were treated at a dedicated neurological ICU following institutional standard operating procedures. A good clinical outcome was defined as a modified Rankin scale score of 0-2 after 3 months. Univariate and multivariate analyses were applied using outcome parameters as dependent variables and baseline variables with a significant p value in univariate tests as independent variables. Results: One hundred eleven patients (BAO-1) were treated before and 36 were treated after July 2009 (BAO-2). Patients in the BAO-1 and BAO-2 groups had similar neurological deficits on admission as expressed by the Glasgow Coma Scale (BAO-1: median 4, IQR 5, vs. BAO-2: median 4.5, IQR 8, p = 0.41) and the proportion of patients who were presented intubated and ventilated was similar in both groups as well (49.5 vs. 47.7%, p = 0.85). Bridging concepts with intravenous recombinant tissue plasminogen activator (rtPA) were applied in 18.9% (BAO-1) versus 63.9% (BAO-2, p < 0.001) of cases, whereas glycoprotein IIb/IIIa antagonists were used significantly more frequently in the BAO-1 cohort (57.7 vs. 33.3%, p = 0.034). Thrombectomies were performed in 20 patients (55.5%) of the BAO-2 group but in none of the BAO-1 cohort. Complete recanalization (TICI 3) was achieved in 45.1% (BAO-1) versus 66.7% (BAO-2, p = 0.062) of patients. A good clinical outcome was observed in 13.5% of the BAO-1 group and 30.6% of the BAO-2 cohort (p = 0.026); mortality was 57.7% in the earlier group and 36.1% in the later group (p = 0.034). The frequency of symptomatic intracranial hemorrhage was similar in both groups (8.1% BAO-1 vs. 2.8% BAO-2, p = 0.45). Treatment in the BAO-2 cohort was an independent predictor of good clinical outcome (OR 2.56; 95% CI 1.01-6.78) and mortality (OR 0.36; 95% CI 0.15-0.86) in an adjusted logistic regression model. Conclusion: Our results show improved outcomes in patients in the BAO-2 cohort. The treatment approach in this group was an independent predictor of both good outcome and mortality. Especially in patients with BAO - where endovascular treatment strategies are common clinical practice - bridging protocols with rtPA and modern thrombectomy devices should be used more frequently. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Hypothermia is one of the most robust experimental neuroprotective interventions against cerebral ischemia. Identification of molecular pathways and gene networks together with single genes or gene families that are significantly associated with neuroprotection might help unravel the mechanisms of therapeutic hypothermia. Material and Methods: We performed a microarray analysis of ischemic rat brains that underwent 90 min of middle cerebral artery occlusion (MCAO) and 48 h of reperfusion. Hypothermia was induced for 4 h, starting 1 h after MCAO in male Wistar rats. At 48 h, magnetic resonance imaging (MRI) was performed for infarct volumetry, and functional outcome was determined by a neuroscore. The brain gene expression profile of sham (S), ischemia (I), and ischemia plus hypothermia (HI) treatment were compared by analyzing changes of individual genes, pathways, and networks. Real-time reverse-transcribed polymerase chain reaction (RT-PCR) was performed on selected genes to validate the data. Results: Rats treated with HI had significantly reduced infarct volumes and improved neuroscores at 48 h compared with I. Of 4067 genes present on the array chip, HI compared with I upregulated 50 (1.23%) genes and downregulated 103 (3.20%) genes equal or greater than twofold. New genes potentially mediating neuroprotection by hypothermia were HNRNPAB, HIG-1, and JAK3. On the pathway level, HI globally suppressed the ischemia-driven gene response. Twelve gene networks were identified to be significantly altered by HI compared with I. The most significantly altered network contained genes participating in apoptosis suppression. Conclusions: Our data suggest that although hypothermia at the pathway level restored gene expression to sham levels, it selectively regulated the expression of several genes implicated in protein synthesis and folding, calcium homeostasis, cellular and synaptic integrity, inflammation, cell death, and apoptosis. [Copyright &y& Elsevier]

A letter to the editor is presented which discusses the identification of novel non-T-cell receptor (TCR) chromosome translocations t(X;11)(q25;p13) and t(3;11)(q25;p13) activating LIM-domain-only-2 gene (LMO2) by stromal antigen 2 (STAG2) and muscleblind-like protein 1 (MBNL1) genes' juxtaposition.

Abstract: Blood–brain-barrier (BBB) breakdown due to matrix metalloproteinase (MMP) activity following stroke is often associated with cerebral edema, larger infarct volumes and bad outcome. In the present study we examined a novel MMP-inhibitor (Ro 28-2653) with high selectivity for MMP2, MMP9 and membrane type 1-MMP in an acute stroke model comparing two different treatment regimens. We subjected rats to 90min of focal cerebral ischemia followed by 3days or 7days of reperfusion, respectively, using the middle cerebral artery (MCA) filament occlusion technique. Ro 28-2653 was administered daily in a vehicle solution for 2days or 6days after ischemia, respectively. We assessed the behavior with a functional neuroscore and infarct volumes as well as blood–brain-barrier (BBB) breakdown with magnetic resonance imaging (MRI) after 3 and 7days. Infarct edema volumes, BBB breakdown and behavior at 3days were significantly attenuated in rats treated for 2days with Ro 28-2653 as compared to vehicle and untreated controls. After 6days of treatment however, infarct and BBB breakdown volumes as well as behavior did not differ significantly between the groups at 7days. The new high selective MMP-inhibitor Ro 28-2653 significantly reduced brain injury only when administered in the first 2days after focal cerebral ischemia. Prolonged treatment for 6days did not show any beneficial effects possibly due to interference with protective restorative processes. [ABSTRACT FROM AUTHOR]

The transport of relativistic electrons generated in the interaction of petawatt class lasers with solid targets has been studied through measurements of the second harmonic optical emission from their rear surface. The high degree of polarization of the emission indicates that it is predominantly optical transition radiation (TR). A halo that surrounds the main region of emission is also polarized and is attributed to the effect of electron recirculation. The variation of the polarization state and intensity of radiation with the angle of observation indicates that the emission of TR is highly directional and provides evidence for the presence of μm-size filaments. A brief discussion on the possible causes of such a fine electron beam structure is given. [ABSTRACT FROM AUTHOR]

The dilation x-ray imager (DIXI) [T. J. Hilsabeck et al., Rev. Sci. Instrum. 81, 10E317 (2010); S. R. Nagel et al., ibid. 83, 10E116 (2012); S. R. Nagel et al., ibid. 85, 11E504 (2014)] is a high-speed x-ray framing camera that uses the pulse-dilation technique to achieve a temporal resolution of less than 10 ps. This is a 10× improvement over conventional framing cameras currently employed on the National Ignition Facility (NIF) (100 ps resolution), and otherwise only achievable with 1D streaked imaging. A side effect of the dramatically reduced gate width is the comparatively lower detected signal level. Therefore we implement a Poisson noise reduction with non-local principal component analysis method [J. Salmon et al., J. Math. Imaging Vision 48, 279294 (2014)] to improve the robustness of the DIXI data analysis. Here we present results on ignition-relevant experiments at the NIF using DIXI. In particular we focus on establishing that/when DIXI gives reliable shape metrics (P0, P2, and P4 Legendre modes, and their temporal evolution/swings). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a new chromosome arrangement of the NOTCH1 in the cell line of T-cell acute lymphocytic leukemia (T-ALL).

A letter to the editor is presented in response to the article "t(3;7)(q27;q32) Fuses BCL6 to a Non-Coding Region at FRA7H Near miR-29," in the November 8, 2007 issue.

In T-cell acute lymphoblastic leukemia (T-ALL) the cardiac homeobox gene NKX2-5 (at 5q35) is variously deregulated by regulatory elements coordinating with BCL11B (at 14q32.2), or the T-cell receptor gene TRD (at 14q11.2), respectively. NKX2-5 is normally expressed in developing spleen and heart, regulating fundamental processes, including differentiation and survival. In this study we investigated whether NKX2-5 expression in T-ALL cell lines reactivates these embryonal pathways contributing to leukemogenesis. Among 18 known targets analyzed, we identified three genes regulated by NKX2-5 in T-ALL cells, including myocyte enhancer factor 2C (MEF2C). Knockdown and overexpression assays confirmed MEF2C activation by NKX2-5 at both the RNA and protein levels. Direct interactions between NKX2-5 and GATA3 as indicated by co-immunoprecipitation data may contribute to MEF2C regulation. In T-ALL cell lines LOUCY and RPMI-8402 MEF2C expression was correlated with a 5q14 deletion, encompassing noncoding proximal gene regions. Fusion constructs with green fluorescent protein permitted subcellular detection of MEF2C protein in nuclear speckles interpretable as repression complexes. MEF2C consistently inhibits expression of NR4A1/NUR77, which regulates apoptosis via BCL2 transformation. Taken together, our data identify distinct mechanisms underlying ectopic MEF2C expression in T-ALL, either as a downstream target of NKX2-5, or via chromosomal aberrations deleting proximal gene regions. [ABSTRACT FROM AUTHOR]

Recurrent chromosomal aberrations in hematopoietic tumors target genes involved in pathogenesis. Their identification and functional characterization are therefore important for the establishment of rational therapies. Here, we investigated genomic amplification at 7q22 in the T-cell lymphoma cell line SU-DHL-1 belonging to the subtype of anaplastic large-cell lymphoma (ALCL). Cytogenetic analysis mapped this amplicon to 86–95 Mb. Copy-number determination quantified the amplification level at 5- to 6-fold. Expression analysis of genes located within this region identified cyclin-dependent kinase 6 (CDK6) as a potential amplification target. In comparison with control cell lines, SU-DHL-1 expressed considerably higher levels of CDK6. Functionally, SU-DHL-1 cells exhibited reduced sensitivity to rapamycin treatment, as indicated by cell growth and cell cycle analysis. Rapamycin reportedly inhibits degradation of the CDK inhibitor p27 with concomitant downregulation of cyclin D3, implying a proliferative advantage for CDK6 overexpression. Amplification of the CDK6 locus was analyzed in primary T-cell lymphoma samples and, while detected infrequently in those classified as ALCL (1%), was detected in 23% of peripheral T-cell lymphomas not otherwise specified. Taken together, analysis of the 7q22 amplicon identified CDK6 as an important cell cycle regulator in T-cell lymphomas, representing a novel potential target for rational therapy.Leukemia (2008) 22, 387–392; doi:10.1038/sj.leu.2405028; published online 8 November 2007 [ABSTRACT FROM AUTHOR]

Multiple cytokines are secreted by Hodgkin lymphoma (HL) cells, notably interleukin-6 (IL6), which is believed to play a significant pathobiological role in this and certain other tumors. Previous work on prostate carcinoma cells has shown that IL6 expression is activated therein by the homeodomain protein GBX2, which we found to be absent in HL cells. Instead, we observed expression of a closely related gene, HLXB9, albeit restricted to HL cells coexpressing IL6. Treatment of HL cell lines with antisense-oligonucleotides directed against HLXB9, forced expression of recombinant HLXB9, and analysis of reporter gene constructs containing IL6 promoter sequences all confirmed the potential of HLXB9 to drive expression of IL6. Chromosomal rearrangements of the HLXB9 locus at 7q36 were not detected in HL cells unlike AML subsets expressing HLXB9. However, inhibition of certain signal transduction pathways revealed that the phosphatidylinositol 3 kinase (PI3K) pathway contributes to HLXB9 expression. AKT/phospho-AKT analysis revealed constitutively active PI3K signalling in HL cell lines. Downstream analysis of PI3K revealed that E2F3 may mediate activation of HLXB9. Taken together, our data show that the PI3K signalling pathway in HL cells is constitutively activated and promotes HLXB9 expression, probably via E2F3, thereby enhancing malignant expression of IL6.Leukemia (2005) 19, 841-846. doi:10.1038/sj.leu.2403716 Published online 17 March 2005 [ABSTRACT FROM AUTHOR]

The time-resolved x-ray diffraction platform at the National Ignition Facility (NIF) fields electronic sensors closer to the exploding laser-driven target than any other NIF diagnostic in order to directly detect diffracted x rays from highly compressed materials. We document strategies to characterize and mitigate the unacceptably high background signals observed in this geometry. We specifically assess the possible effects of electromagnetic pulse, x-ray fluorescence, hot electrons, and sensor-specific non-x-ray artifacts. Significant background reduction is achieved by strategic shielding. [ABSTRACT FROM AUTHOR]

As part of a program to measure phase transition timescales in materials under dynamic compression, we have designed new x-ray imaging diagnostics to record multiple x-ray diffraction measurements during a single laser-driven experiment. Our design places several ns-gated hybrid CMOS (hCMOS) sensors within a few cm of a laser-driven target. The sensors must be protected from an extremely harsh environment, including debris, electromagnetic pulses, and unconverted laser light. Another key challenge is reducing the x-ray background relative to the faint diffraction signal. Building on the success of our predecessor (Target Diffraction In Situ), we implemented a staged approach to platform development. First, we built a demonstration diagnostic (Gated Diffraction Development Diagnostic) with two hCMOS sensors to confirm we could adequately protect them from the harsh environment and also acquire acceptable diffraction data. This allowed the team to quickly assess the risks and address the most significant challenges. We also collected scientifically useful data during development. Leveraging what we learned, we recently developed a much more ambitious instrument (Flexible Imaging Diffraction Diagnostic for Laser Experiments) that can field up to eight hCMOS sensors in a flexible geometry and participate in back-to-back shots at the National Ignition Facility (NIF). The design also allows for future iterations, such as faster hCMOS sensors and an embedded x-ray streak camera. The enhanced capabilities of the new instrument required a much more complex design, and the unexpected issues encountered on the first few shots at NIF remind us that complexity has consequences. Our progress in addressing these challenges is described herein, as is our current focus on improving data quality by reducing x-ray background and quantifying the uncertainties of our diffraction measurements. [ABSTRACT FROM AUTHOR]

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a new diagnostic at the National Ignition Facility (NIF) designed to observe in situ solid–solid phase changes at high pressures using time resolved x-ray diffraction. FIDDLE currently incorporates five Icarus ultrafast x-ray imager sensors that take 2 ns snapshots and can be tuned to collect X-rays for tens of ns. The platform utilizes the laser power at NIF for both the laser drive and the generation of 10 keV X-rays for ∼10 ns using a Ge backlighter foil. We aim to use FIDDLE to observe diffraction at different times during compression to probe the kinetics of phase changes. Pb undergoes two solid–solid phase transitions during ramp compression: from face centered cubic (FCC) to hexagonal close packed (HCP) and HCP to body centered cubic (BCC). Results will be reported on some of the first shots using the FIDDLE diagnostic at NIF on ramp compressed Pb to a peak pressure of ∼110 GPa and a single undriven CeO2 calibration shot. A discussion of the uncertainties in the observed diffraction is included. [ABSTRACT FROM AUTHOR]

We are developing techniques for studying the Rayleigh–Taylor (RT) and Richtmyer–Meshkov (RM) instabilities in a planar geometry at high-energy-densities at the National Ignition Facility (NIF). In particular, through the improvement of experimental imaging quality, we are progressing toward the study of the turbulent regime of the mixing regions in capsule implosion experiments for inertial confinement fusion, which requires few micrometers resolution. Using 60 NIF beams, a solid shock tube is driven launching a shock wave that crosses the interface between a dense and a light material pre-machined in the target to obtain sinusoidal ripples, which results in RM and RT instabilities that are imaged using the NIF Crystal Backlighter Imager. High-quality images were obtained with a mean resolution of 7 μm and improved contrast. While the obtained resolution does not allow the observation of the smallest scale of the "turbulent" energy spectrum, the generated image encompasses 63% of the total flow energy, a 50% improvement over previous studies, which is observed for the first time a roll-up feature in a high energy density-type RT experiment. [ABSTRACT FROM AUTHOR]

Hardened gated x-ray detectors use photographic film as the data recording medium due to its low sensitivity to the high-yield neutron environments at the National Ignition Facility (NIF). The photographic film is digitized with a Photometric Data Systems (PDS) microdensitometer, which measures the film's optical density. The PDS scanner is able to measure a dynamic range of 0–5 OD; however, raster scanning the film is time consuming and maintenance of the instrument is challenging due to legacy technology. Since film usage at NIF is expected to continue in the foreseeable future, a digitization platform that is faster and more maintainable would benefit the NIF's current and future operations. This work presents the characterization of the digital transitions (DT) atom, a CMOS camera-based digitization platform that records film data in a single image capture very quickly and has widely available user support. The preliminary results suggest that the DT atom is able to reconstruct exposures accurately enough to be a competitive alternative to the PDS Scanner. [ABSTRACT FROM AUTHOR]

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a newly developed diagnostic for imaging time resolved diffraction in experiments at the National Ignition Facility (NIF). It builds on the successes of its predecessor, the Gated Diffraction Development Diagnostic (G3D). The FIDDLE was designed to support eight Daedalus version 2 sensors (six more hCMOS sensors than any other hCMOS-based diagnostic in NIF to date) and an integrated streak camera. We will review the electrical requirements, design, and performance of the electrical subsystems that were created to support this large number of cameras in the FIDDLE. The analysis of the data that the FIDDLE is intended to collect relies heavily on the accurate and well-understood timing of each sensor. We report camera-to-camera timing jitter of less than 100 ps rms and sensor integration times of 2.2 ns FWHM in 2-2 timing mode. Additionally, diffraction experiments on the NIF produce electric fields (EMI) on the order of 1 kV/m, which have been observed to negatively impact the performance of some electrical components of the FIDDLE. We report on the results of testing hCMOS camera electronics in a similar EMI environment generated in an offline lab. We also summarize the use of a novel approach to using a vector network analyzer as an EMI leak detector to understand and reduce the negative impacts of EMI on the FIDDLE. [ABSTRACT FROM AUTHOR]

The interface between the capsule ablator and fuel ice layer is susceptible to hydrodynamic instabilities. The subsequent mixing of hot ablator material into the ice reduces fuel compression at stagnation and is a candidate for reduced capsule performance. The ability to diagnose ice–ablator mix is critical to understanding and improving stability at this interface. Combining the crystal backlighter imager with the single line of sight camera on the National Ignition Facility (NIF) allows direct measurement of ice–ablator mix by providing multiple quasi-monochromatic radiographs of layered capsule implosions per experiment with high spatial (∼12 μm) and temporal (∼35 ps) resolution. The narrow bandwidth of this diagnostic platform allows radiography of the inner edge of the capsule limb close to stagnation without capsule self-emission contaminating the data and removes opacity uncertainties typically associated with the spectral content of the radiograph. Analysis of radiographic data via a parameterized forward-fitting Abel inversion technique provides measurements of the distribution of mix mass inwards from the ice–ablator interface. The sensitivity of this mix measurement technique was demonstrated by applying it to layered experiments in which the stability of the ice–ablator interface was expected to vary significantly. Additional experiments suggest that high-density carbon capsules that employ a buried-layer dopant profile suffer from mixing at the innermost doped–undoped interface. Data from these experiments suggest that opacity models used in hydrodynamic simulations of NIF experiments can potentially over-predict the opacity of doped capsules. LLNL-JRNL-850535-DRAFT. [ABSTRACT FROM AUTHOR]

Nanosecond-gated hybrid complementary metal-oxide semiconductor imaging sensors are a powerful tool for temporally gated and spatially resolved measurements in high energy density science, including inertial confinement fusion, and in laser diagnostics. However, a significant oscillating background excited by photocurrent has been observed in image sequences during testing and in experiments at the National Ignition Facility (NIF). Characterization measurements and simulation results are used to explain the oscillations as the convolution of the pixel-level sensor response with a sensor-wide RLC circuit ringing. Data correction techniques are discussed for NIF diagnostics, and for diagnostics where these techniques cannot be used, a proof-of-principle image correction algorithm is presented. [ABSTRACT FROM AUTHOR]

Copper activation was used to characterize high-energy proton beam acceleration from near-critical density plasma targets. An enhancement was observed when decreasing the target density, which is indicative for an increased laser-accelerated hot electron density at the rear target-vacuum boundary. This is due to channel formation and collimation of the hot electrons inside the target. Particle-in-cell simulations support the experimental observations and show the correlation between channel depth and longitudinal electric field strength is directly correlated with the proton acceleration. [ABSTRACT FROM AUTHOR]

The effects of pre-plasmas on the electron beam directionality was experimentally and numerically investigated. Single material and layered targets made of Ti and/or CH were used to simultaneously measure high-energy (≥ 3 MeV) electrons along two directions, pre-pulse energy and pre-plasma density. The electron directionality is quantified by using a new parameter, the electron energy ratio of the total kinetic energies along the two directions. Measurements and radiation–hydrodynamic (RH) simulations show that a large (≥ 3.5 μ m) plasma scale length at the critical surface enhances electrons along the laser axis, and such pre-plasma conditions could only be achieved with the CH targets. Particle-in-cell simulations were performed on the RH generated pre-plasmas from Ti and CH targets, and the results show that the CH target provided conditions for higher forward momentum gains by electrons. First, the CH target allowed longer distances for electrons to interact with laser. Second, the intense laser pulse modified the critical surface, but the resulting surface differed. The CH target resulted in a smooth surface where a retro-reflection was observed while the Ti target resulted in a rippled surface that scattered the reflected light. As results, the CH electrons gained higher forward momentum via a direct-laser-acceleration in the counter propagating laser fields. The results presented in this article show a way of controlling the high-energy electron directionality. [ABSTRACT FROM AUTHOR]

A Kentech x-ray streak camera was run at the LLNL compact multipulse terawatt (COMET) laser to record simultaneous space- and time-resolved measurements of picosecond laser-produced plasmas. Four different x-ray energy channels were monitored using broadband filters to record the time history of Cu targets heated at irradiances of 1016-1019 W/cm2. Through the Cu filter channel, a time-resolution below 3 ps was obtained. Additionally, an array of 10 μm diameter pinholes was placed in front of the camera to produce multiple time-resolved x-ray images on the photocathode and time-integrated images on the phosphor with 10 and 15 times magnification, respectively, with spatial resolution of < 13 μm. [ABSTRACT FROM AUTHOR]

As the yield on implosion shots increases it is expected that the peak x-ray emission reduces to a duration with a FWHM as short as 20 ps for ∼7 × 1018 neutron yield. However, the temporal resolution of currently used gated x-ray imagers on the NIF is 40-100 ps. We discuss the benefits of the higher temporal resolution for the NIF and present performance measurements for dilation x-ray imager, which utilizes pulse-dilation technology [T. J. Hilsabeck et al., Rev. Sci. Instrum. 81, 10E317 (2010)] to achieve x-ray imaging with temporal gate times below 10 ps. The measurements were conducted using the COMET laser, which is part of the Jupiter Laser Facility at the Lawrence Livermore National Laboratory. [ABSTRACT FROM AUTHOR]

The oomycete Phytophthora sojae is a severe pathogen of soybean. Several resistance genes against races of P. sojae exist in soybean but the nature of corresponding avirulence genes is unknown. Clones encoding four different isoforms of a protein elicitor from P. sojae (sojein 1–4) belonging to the class of acidic α-elicitins have been isolated. These 98 amino acid proteins show high homology to elicitins from other Phytophthora species. The different sojein isoforms were expressed in Escherichia coli as His-tagged fusion proteins. Purified sojein as well as recombinant sojein isoforms induce hypersensitive reaction (HR)-like lesions in tobacco but are not active as race-specific elicitors in soybean. However all sojein isoforms induce defence-related genes like those encoding phenylalanine ammonia lyase, glutathione-S-transferase and chalcone synthase in tobacco and soybean plants and cell cultures. It is concluded that sojeins contribute to the induction of defence responses but that they are not involved in race specific recognition of the P. sojae races by soybean plants. [ABSTRACT FROM AUTHOR]

This study investigates methods to optimize quasi-monochromatic, ∼10 ns long x-ray sources (XRS) for time-resolved x-ray diffraction measurements of phase transitions during dynamic laser compression measurements at the National Ignition Facility (NIF). To support this, we produce continuous and pulsed XRS by irradiating a Ge foil with NIF lasers to achieve an intensity of 2 × 1015 W/cm2, optimizing the laser-to-x-ray conversion efficiency. Our x-ray source is dominated by Ge He-α line emission. We discuss methods to optimize the source to maintain a uniform XRS for ∼10 ns, mitigating cold plasma and higher energy x-ray emission lines. [ABSTRACT FROM AUTHOR]

In view of the changes in and growing variety of sports-related occupations, it is highly relevant for educational institutions to know how well the educational contents of their sport science courses meet the professional requirements. This study analyses the relationship between the competencies acquired through academic sports science courses and the requirements of the relevant jobs in Switzerland. The data for this empirical analysis were drawn from a sample of n = 1054 graduates of different academic sport science programmes at all eight Swiss universities. The results show that academic sport science courses primarily communicate sports-specific expertise and practical sports skills. On the other hand, most graduates consider that the acquisition of interdisciplinary competencies plays a comparatively minor role in sport science education, even though these competencies are felt to be an important requirement in a variety of work-related environments and challenges. [ABSTRACT FROM AUTHOR]

The neuroblastoma (NB) cell lines such as SH-SY5Y have been widely used as in vitro neuron model to evaluate mutation impact on neuron formation or morphology in many types of neuromuscular disorders. However, it also raised concerns as the cell lines are derived from malignant tumours. Meanwhile the induced pluripotent stem cell (iPSC)-derived neurons showed great potential in disease modelling due to the tumour-free background and more clinical relevance. To provide a general guide on neuron model selection for neuromuscular disorders (NMD), we made a systematical characterization of 17 NB cell lines from our cell bank, and also compared the NB-derived neurons with iPSC-derived neurons. Using RNA-seq, we identified key disease-causing mutations associated with neuroblastoma and additional mutations which might impact on mature neuron functions. The NB cell lines were grouped into adrenergic (ADRN) and mesenchymal (MES) types based on gene expression profiling and their response to retinoic acid (RA). The mature neurons derived from ADRN NB cell lines showed expression of common neuronal markers such as class III β-tubulin, neurofilaments, and preferential expression of certain neuromuscular disorder related genes such as SLC5A7. On the other hand, the iPSC-derived neurons required longer and complicated differentiation process to achieve the mature neuron status. In summary, our comprehensive study demonstrated that the type of NB cell line, its tumour-associated mutations and individual NMD gene expression pattern represent key factors for the selection of a suitable NMD neuron model. Furthermore, the NB neuron models promise low morphology variability and enable high throughput application while the iPSC-derived neurons are more suitable for the validation of pathophysiological relevance. [ABSTRACT FROM AUTHOR]

The hardened single line of sight camera has been recently characterized in preparation for its deployment on the National Ignition Facility. The latest creation based on the pulse-dilation technology leads to many new features and improvements over the previous-generation cameras to provide better quality measurements of inertial confinement fusion experiments, including during high neutron yield implosions. Here, we present the characterization data that illustrate the main performance features of this instrument, such as extended dynamic range and adjustable internal magnification, leading to improved spatial resolution. [ABSTRACT FROM AUTHOR]

Background: Cerebral venous and sinus thrombosis (CVST) constitutes less than 0.5-1 % of all strokes and occurs predominantly in young female adults. In general the clinical outcome is favorable but 3-15 % of patients die in the acute phase and in the majority of cases due to cerebral herniation. Intensive care treatment analogous to that of severe ischemic infarct leads to an aggressive interdisciplinary therapy concept that can achieve good clinical outcome. Based on five cases of severe CVST treatment options will be presented. Results: All five patients were affected by impending or incipient cerebral herniation and severe focal neurological deficits which resulted in the decision to implement thrombectomy, thrombolysis or hemicraniectomy. Despite the severe course and many intensive care complications which suggested a poor prognosis, all five patients could be transferred to rehabilitation after having survived the acute phase and achieved an amazingly good overall clinical outcome. Conclusion: Considering the life-threatening course of severe CVST, aggressive interdisciplinary management by endovascular thrombectomy and hemicraniectomy can lead to a scarcely expected clinical outcome without disability or severe dependency. This treatment should be performed early and in an escalatory manner in patients with severe CVST who have an increased risk of an unfavorable outcome due to edema, infarction and hemorrhage. [ABSTRACT FROM AUTHOR]

Objectives: Artif icial intelligence (AI)–based image analysis is increasingly applied in the acute stroke field. Its implementation for the detection and quantification of hemorrhage suspect hyperdensities in non-contrast-enhanced head CT (NCCT) scans may facilitate clinical decision-making and accelerate stroke management. Methods: NCCTs of 160 patients with suspected acute stroke were analyzed regarding the presence or absence of acute intracranial hemorrhages (ICH) using a novel AI-based algorithm. Read was performed by two blinded neuroradiology residents (R1 and R2). Ground truth was established by an expert neuroradiologist. Specificity, sensitivity, and area under the curve were calculated for ICH and intraparenchymal hemorrhage (IPH) detection. IPH-volumes were segmented and quantified automatically by the algorithm and semi-automatically. Intraclass correlation coefficient (ICC) and Dice coefficient (DC) were calculated. Results: In total, 79 of 160 patients showed acute ICH, while 47 had IPH. Sensitivity and specificity for ICH detection were 0.91 and 0.89 for the algorithm; 0.99 and 0.98 for R1; and 1.00 and 0.98 for R2. Sensitivity and specificity for IPH detection were 0.98 and 0.89 for the algorithm; 0.83 and 0.99 for R1; and 0.91 and 0.99 for R2. Interreader reliability for ICH and IPH detection showed strong agreements for the algorithm (0.80 and 0.84), R1 (0.96 and 0.84), and R2 (0.98 and 0.92), respectively. ICC indicated an excellent (0.98) agreement between the algorithm and the reference standard of the IPH-volumes. The mean DC was 0.82. Conclusion: The AI-based algorithm reliably assessed the presence or absence of acute ICHs in this dataset and quantified IPH volumes precisely. Key Points: • Artificial intelligence (AI) is able to detect hyperdense volumes on brain CTs reliably. • Sensitivity and specificity are highest for the detection of intraparenchymal hemorrhages. • Interreader reliability for hemorrhage detection shows strong agreement for AI and human readers. [ABSTRACT FROM AUTHOR]

We report experimental evidence for a Rayleigh-Taylor-like instability driven by radiation pressure of an ultraintense (1021 W/cm2) laser pulse. The instability is witnessed by the highly modulated profile of the accelerated proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C, 10% H) target. Clear anticorrelation between bubblelike modulations of the proton beam and transmitted laser profile further demonstrate the role of the radiation pressure in modulating the foil. Measurements of the modulation wavelength, and of the acceleration from Doppler-broadening of back-reflected light, agree quantitatively with particle-in-cell simulations performed for our experimental parameters and which confirm the existence of this instability. [ABSTRACT FROM AUTHOR]

Background: Recently, several studies using diffusion-sensitized MRI reported changes in patients with high-grade internal carotid artery stenosis (ICAS) suggestive of subtle brain tissue damage. We used diffusion tensor imaging (DTI) to investigate the microstructural cerebral white matter integrity in asymptomatic patients with high-grade ICAS. Methods: In 15 asymptomatic patients with unilateral high grade (>70%) ICAS, we used 3T MRI including DTI. We used a region-of-interest approach comparing quantitative DTI metrics between both hemispheres including the so-called border zones. MR images were also assessed for periventricular white matter lesions (PWML) as well as collaterals via the circle of Willis. Results: There was no significant intraindividual difference of fractional anisotropy or mean diffusivity values between the hemispheres for any region. PWML was graded 0° in 6 patients, I° in 9 and II° in 2. Conclusions: In clinically asymptomatic patients with high-grade unilateral ICAS, there was no difference between the DTI parameters of the affected and the unaffected hemisphere. These findings contrast with other studies in asymptomatic high-grade ICAS, which is likely due to patient selection. These findings argue against concomitant chronic tissue integrity changes and implicate the benignity of asymptomatic carotid artery disease in individual patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A new generation of gated x-ray detectors at the National Ignition Facility has brought faster, enhanced imaging capabilities. Their performance is currently limited by the amount of signal they can be operated with before space charge effects in their electron tube start to compromise their temporal and spatial response. We present a technique to characterize this phenomenon and apply it to a prototype of such a system, the Single Line Of Sight camera. The results of this characterization are used to benchmark particle-in-cell simulations of the electrons drifting inside the detector, which are found to well reproduce the experimental data. These simulations are then employed to predict the optimum photon flux to the camera, with the goal to increase the quality of the images obtained on an experimental campaign while preventing the appearance of deleterious effects. They also offer some insights into some of the improvements that can be brought to the new pulse-dilation systems being built at Lawrence Livermore National Laboratory. [ABSTRACT FROM AUTHOR]

The chromosomal translocation t(8;21)(q22;q22) is one of the most frequent karyotypic aberrations in acute myeloid leukemia (AML) and results in a chimeric fusion transcript AML1/MTG8. Since AML1/MTG8 fusion transcripts remain detectable by RT-PCR in t(8;21) AML patients in long-term hematological remission, quantitative assessment of AML1/MTG8 transcripts is necessary for the monitoring of minimal residual disease (MRD) in these patients. Competitive RT-PCR and recently real-time RT-PCR are increasingly used for detection and quantification of leukemia specific fusion transcripts. For the direct comparison of both methods we cloned a 42 bp DNA fragment into the original AML1/MTG8 sequence. The resulting molecule was used as an internal competitor for our novel competitive nested RT-PCR for AML1/MTG8 and as an external standard for the generation of AML1/MTG8 standard curves in a real-time PCR assay. Using this standard molecule for both PCR techniques, we compared their sensitivity, linearity and reproducibility. Both methods were comparable with regard to all parameters tested irrespective of analyzing serial dilutions of plasmids, cell lines or samples from t(8;21) positive AML patients at different stages of the disease. Therefore, both techniques can be recommended for the monitoring of MRD in these particular AML patients. However, the automatization of the real-time PCR technique offers some technical advantages. [ABSTRACT FROM AUTHOR]

We present the results of experiments to produce a 10 ns-long, quasi-monochromatic x-ray source. This effort is needed to support time-resolved x-ray diffraction (XRDt) measurements of phase transitions during laser-driven dynamic compression experiments at the National Ignition Facility. To record XRDt of phase transitions as they occur, we use high-speed (∼1 ns) gated hybrid CMOS detectors, which record multiple frames of data over a timescale of a few to tens of ns. Consequently, to make effective use of these imagers, XRDt needs the x-ray source to be narrow in energy and uniform in time as long as the sensors are active. The x-ray source is produced by a laser irradiated Ge foil. Our results indicate that the x-ray source lasts during the whole duration of the main laser pulse. Both time-resolved and time-integrated spectral data indicate that the line emission is dominated by the He-α complex over higher energy emission lines. Time-integrated spectra agree well with a one-dimensional Cartesian simulation using HYDRA that predicts a conversion efficiency of 0.56% when the incident intensity is 2 × 1015 W/cm2 on a Ge backlighter. [ABSTRACT FROM AUTHOR]

Being able to provide high-resolution x-ray radiography is crucial in order to study hydrodynamic instabilities in the high-energy density regime at the National Ignition Facility (NIF). Current capabilities limit us to about 20 μm resolution using pinholes, but recent studies have demonstrated the high-resolution capability of the Fresnel zone plate optics at the NIF, measuring 2.3 μm resolution. Using a zinc Heα line at 9 keV as a backlighter, we obtained a radiograph of Rayleigh–Taylor instabilities with a measured resolution of under 3 μm. Two images were taken with a time integrated detector and were time gated by a laser pulse duration of 600 ps, and a third image was taken with a framing camera with a 100 ps time gate on the same shot and on the same line of sight. The limiting factors on image quality for these two cases are the motion blur and the signal to noise ratio, respectively. We also suggest solutions to increase the image quality. [ABSTRACT FROM AUTHOR]

We are developing ovine models of spinal cord injury to test novel neuromodulation-based methods on spasticity. The hemisection has been reported in a number of large animal studies. Our aim is to duplicate a hemisection injury in the sheep. Our effort is explored here. Methods and Results: Three sheep underwent hemi-sectioning of the spinal cord. Quantitative gait analysis was completed both pre- and post-injury. While measurable differences in most of the 20 gait metrics were observed, relatively few were above the predicted thresholds based on error levels expected from the data. Variations in severity of injury across the three sheep were observed. Conclusions: The hemisection ovine model of spinal cord injury shows promise as a large-animal platform for developing new therapies for treating spinal cord injuries. While variability in injury severity was observed across animals, as has been observed with weight drop-based SCI models, the hemi-section approach has the advantages of procedural ease and reduced technical complexity. [ABSTRACT FROM AUTHOR]

Introduction The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges. Methods A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain. Results To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative. Conclusions Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy. [ABSTRACT FROM AUTHOR]

Background and purpose: Although patient‐centredness is considered a key component of high‐quality neurological care, it is unclear to what extent it can or should be implemented during the acute phase. Using acute stroke as an example, the aim was to identify critical junctures for patient‐centredness along the acute care pathway from the perspectives of patients, relatives and staff. Methods: A qualitative multi‐method study was conducted including 27 non‐participant observations and 37 semi‐structured interviews with patients, relatives and staff. Junctures were defined as critical when mentioned (as problematic) in two or three information sources (i.e. observations, staff interviews, or patient and relative interviews), as potentially critical when mentioned in one, and as uncritical when not mentioned. Results: Post‐procedure communication after thrombectomy, patients' stay at the stroke unit and decision‐making around transfer, discharge and rehabilitation were identified as critical junctures for patient‐centredness. Arrival at the emergency department and the (thrombectomy) treatment itself were identified as uncritical junctures, whilst history‐taking and treatment preparation, the treatment decision and patients' stay at the intensive care unit were identified as potentially critical junctures. Conclusions: In acute stroke care, patients, relatives and staff prioritize fast over patient‐centred decision‐making in the most time‐critical phases, especially before and during treatment. This is reversed after the procedure, when difficulties arise implementing a patient‐centred approach in clinical practice. To improve patient‐centredness where it is most needed, clear guidelines and accessible resources are recommended. Future research should investigate whether insights from acute phases of stroke care are applicable to other neurological conditions as well. [ABSTRACT FROM AUTHOR]

A hydrodynamic shear mixing layer experiment at the National Ignition Facility had previously demonstrated Eulerian scaling of integrated, late-time quantities, including turbulent kinetic energy. In this manuscript, the experiment is repeated with new materials. Using the new dataset, we demonstrate that Euler-number scalings hold not just for late time, but dynamically throughout the experiment, for measurements in all three spatial dimensions. Incorporating the dynamic scaling leads to an enhanced calculation that the heavier of the two scaled experiments has approached three generations of mergers of its primary instability's structures and a consistent observation of such a merger in action in the lighter of the two scaled experiments. Furthermore, the improved scrutiny of the time evolution of instability structures leads to sharper estimates of turbulent kinetic energy, including a demonstration of different behaviors correlating with surface roughness (quantitatively consistent with transitions between laminar and turbulent initial states), as predicted by a Reynolds-averaged turbulent model, which evidently correctly handles the differing shock-roughness interactions to drive its internal state of the model into different regimes. Altogether, a picture arises of the analytical improvements in treating these variations (of times, densities, and roughnesses) as a unified whole and of multiple ways by which deviations from the scaling could indicate an onset of non-hydrodynamic behavior. Such deviations were not expected for these experiments (which models correctly indicated would remain hydrodynamic) but could be introduced by, for example, imposing external fields or increasing drive energy to test conditions relevant to inertial confinement fusion or other high-energy-density experiments. [ABSTRACT FROM AUTHOR]

The Bigfoot approach to indirect-drive inertial confinement fusion has been developed as a compromise trading high convergence and areal densities for high implosion velocities, large adiabats, and hydrodynamic stability. Shape control and predictability are maintained by using relatively short laser pulses and merging the shocks within the deuterium-tritium-ice layer. These design choices ultimately limit the theoretically achievable performance, and one strategy to increase the 1D performance is to reduce the shell adiabat by extending the pulse shape. However, this can result in the loss of low-mode symmetry control, as the hohlraum "bubble," the high-Z material launched by the outer-cone beams during the early part of the laser pulse, has more time to expand and will eventually intercept inner-cone beams preventing them from reaching the hohlraum waist, thus losing an equatorial capsule drive. Experiments were performed to study the shape control and predictability with extended pulse shapes in Bigfoot implosions, reducing the adiabat from nominally α ∼ 4 to α ∼ 3 and otherwise very similar experimental parameters. The implosion shape was measured both in-flight and at stagnation, with near-round implosions and low levels of P2 asymmetry throughout, indicating a maintained symmetry control with extended pulse shapes. [ABSTRACT FROM AUTHOR]