One-dimensional hydrodynamic simulations of low convergence ratio direct-drive inertial confinement fusion implosions.

Indirect drive inertial confinement fusion experiments with convergence ratios below 17 have been previously shown to be less susceptible to Rayleigh-Taylor hydrodynamic instabilities, making this regime highly interesting for fusion science. Additional limitations imposed on the implosion velocity, in-flight aspect ratio and applied laser power aim to further reduce instability growth, resulting in a new regime where performance can be well represented by one-dimensional (1D) hydrodynamic simulations. A simulation campaign was performed using the 1D radiation-hydrodynamics code HYADES to investigate the performance that could be achieved using direct-drive implosions of liquid layer capsules, over a range of relevant energies. Results include potential gains of 0.19 on LMJ-scale systems and 0.75 on NIF-scale systems, and a reactor-level gain of 54 for an 8.5 MJ implosion. While the use of 1D simulations limits the accuracy of these results, they indicate a sufficiently high level of performance to warrant further investigations and verification of this new low-instability regime. This potentially suggests an attractive new approach to fusion energy. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Systematic Fuel Cavity Asymmetries in Directly Driven Inertial Confinement Fusion Implosions.

We present narrow-band self-emission x-ray images from a titanium tracer layer placed at the fuel-shell interface in 60-laser-beam implosion experiments at the OMEGA facility. The images are acquired during deceleration with inferred convergences of ∼9-14. Novel here is that a systematically observed asymmetry of the emission is linked, using full sphere 3D implosion modeling, to performance-limiting low mode asymmetry of the drive.

First Liquid Layer Inertial Confinement Fusion Implosions at the National Ignition Facility.

The first cryogenic deuterium and deuterium-tritium liquid layer implosions at the National Ignition Facility (NIF) demonstrate D_{2} and DT layer inertial confinement fusion (ICF) implosions that can access a low-to-moderate hot-spot convergence ratio (1230) DT ice layer implosions. Although high CR is desirable in an idealized 1D sense, it amplifies the deleterious effects of asymmetries. To date, these asymmetries prevented the achievement of ignition at the NIF and are the major cause of simulation-experiment disagreement. In the initial liquid layer experiments, high neutron yields were achieved with CRs of 12-17, and the hot-spot formation is well understood, demonstrated by a good agreement between the experimental data and the radiation hydrodynamic simulations. These initial experiments open a new NIF experimental capability that provides an opportunity to explore the relationship between hot-spot convergence ratio and the robustness of hot-spot formation during ICF implosions.

Modeling of a spatially resolved ion temperature diagnostic for inertial confinement fusion.

The performance of modern laser-driven inertial confinement fusion (ICF) experiments is degraded by contamination of the deuterium-tritium (DT) fuel with high-Z material during compression. Simulations suggest that this mix can be described by the ion temperature distribution of the implosion, given that such contaminants deviate in temperature from the surrounding DT plasma. However, existing neutron time-of-flight (nTOF) diagnostics only measure the spatially integrated ion temperature. This paper describes the techniques and forward modeling used to develop a novel diagnostic imaging system to measure the spatially resolved ion temperature of an ICF implosion for the first time. The technique combines methods in neutron imaging and nTOF diagnostics to measure the ion temperature along one spatial dimension at yields currently achievable on the OMEGA laser. A detailed forward model of the source and imaging system was developed to guide instrument design. The model leverages neutron imaging reconstruction algorithms, radiation hydrodynamics and Monte Carlo simulations, optical ray tracing, and more. The results of the forward model agree with the data collected on OMEGA using the completed diagnostic. The analysis of the experimental data is still ongoing and will be discussed in a separate publication.

Instrument design for an inertial confinement fusion ion temperature imager.

A mix of contaminant mass is a known, performance-limiting factor for laser-driven inertial confinement fusion (ICF). It has also recently been shown that the contaminant mass is not necessarily in thermal equilibrium with the deuterium-tritium plasma [B. M. Haines et al., Nat. Commun. 11, 544 (2020)]. Contaminant mass temperature is one of the dominant uncertainties in contaminant mass estimates. The MixIT diagnostic is a new and potentially transformative diagnostic, capable of spatially resolving ion temperature. The approach combines principles of neutron time-of-flight and neutron imaging diagnostics. The information from the MixIT diagnostic can be used to optimize ICF target and laser drive designs as well as provide key constraints on ICF radiation-hydrodynamic simulations that are critical to contaminant mass estimates. This work details the design and optimization of the major components of the MixIT diagnostic: the neutron aperture, the neutron detector (scintillator), and the recording system.

Use of computer vision for analysis of image datasets from high temperature plasma experiments.

Great strides have been made in improving the quality of x-ray radiographs in high energy density plasma experiments, enabled in part by innovations in engineering and manufacturing of integrated circuits and materials. As a consequence, the radiographs of today are filled with a great deal of detail, but few of these features are extracted in a systematic way. Analysis techniques familiar to plasma physicists tend toward brittle 1D lineout or Fourier transform type analyses. The techniques applied to process our data have not kept pace with improvements in the quality of our data. Fortunately, the field of computer vision has a wealth of tools to offer, which have been widely used in industrial imaging and, more recently, adopted in biological imaging. We demonstrate the application of computer vision techniques to the analysis of x-ray radiographs from high energy density plasma experiments, as well as give a brief tutorial on the computer vision techniques themselves. These tools robustly extract 2D contours of shocks, boundaries of inhomogeneities, and secondary flows, thereby allowing for increased automation of analysis, as well as direct and quantitative comparisons with simulations.

Experimental measurement of two copropagating shocks interacting with an unstable interface.

In this work, we present results from experiments capable of producing and measuring the propagation of multiple successive, copropagating shocks across an unstable planar interface, where the shocks are independently driven and separately controllable, enabling the study of this important phenomenon. Copropagating shocks play a significant role in a wide range of systems involving stratified media subject to a shock, and exhibit different physical characteristics compared to counterpropagating shocks. Existing techniques, however, preclude copropagating shocks, so experiments to date have been limited to the study of counterpropagating shocks. We address this previous limitation and open a physical parameter space for study using a new hohlraum platform on the National Ignition Facility. Initial experimental results are presented together with comparisons from numerical simulations.

Targeted resequencing identifies genes with recurrent variation in cerebral palsy.

A growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naïve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP: COL4A1, TUBA1A, AGAP1, L1CAM, MAOB and KIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants, AGAP1, ERLIN1, ZDHHC9 and PROC, of which we functionally assessed AGAP1 using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants.

Intracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifs.

Although many growth factors and cytokines have been shown to be localized within the cell and nucleus, the mechanism by which these molecules elicit a biological response is not well understood. The cytokine leukemia inhibitory factor (LIF) provides a tractable experimental system to investigate this problem, because translation of alternatively spliced transcripts results in the production of differentially localized LIF proteins, one secreted from the cell and acting via cell surface receptors and the other localized within the cell. We have used overexpression analysis to demonstrate that extracellular and intracellular LIF proteins can have distinct cellular activities. Intracellular LIF protein is localized to both nucleus and cytoplasm and when overexpressed induces apoptosis that is inhibited by CrmA but not Bcl-2 expression. Mutational analysis revealed that the intracellular activity was independent of receptor interaction and activation and reliant on a conserved leucine-rich motif that was not required for activation of cell surface receptors by extracellular protein. This provides the first report of alternate intracellular and extracellular cytokine activities that result from differential cellular localization of the protein and are mediated by spatially distinct motifs.

Germline diversity of the expressed BALB/c VhJ558 gene family.

Although the mouse immunoglobulin heavy chain (Igh) locus contains 15 heavy chain V (Vh) gene families, at least half of the Vh gene segments are members of the VhJ558 family. This large Vh gene family represents the least characterized germline coding regions of any of the mouse antigen receptor loci and the contribution of individual VhJ558 genes to the preimmune repertoire is poorly understood. In fact, relatively few germline VhJ558 sequences have been reported for BALB/c, the foundation strain for mouse immunoglobulin genetics and the prototypic strain of the Igh(a) haplotype. Here we present a database consisting of 66 sequences estimated to represent one-half of the total number of functional BALB/c VhJ558 genes. Our results indicate that a subset of the VhJ558 genes is highly expressed in the preimmune repertoire, with just nine Vh sequences accounting for nearly 50% of the VhJ558 heavy chains expressed by splenic B cells. We show that this disparity in the expressed Vh gene repertoire is not due to the position of the Vh genes relative to the Dh cluster or to multiple germline copies of the highly expressed VhJ558 genes. Together, these data constitute the first detailed analysis of functional BALB/c VhJ558 genes, demonstrate a striking bias in the use of particular VhJ558 genes in the preimmune repertoire, and provide sufficient information to study the regulation of the Dh-distal region of the Igh-V locus at the level of individual genes.

Zincophilic root foraging in Thlaspi caerulescens.

• Thlaspi caerulescens hyper-accumulates heavy metals, and localized root proliferation in response to patchily distributed metals may enhance heavy metal uptake. Here, an experimental assessment is made of the impact of heterogeneous zinc (Zn) supply, and of the contrast between the concentration of Zn in soil patches, on Zn hyperaccumulation, patterns of root placement, growth, biomass allocation patterns and nutrient acquisition in two ecotypes of T. caerulescens . • Growth of Prayon and Bradford Dale ecotypes (which originate from a heavily contaminated and a less Zn-contaminated site, respectively) was compared in treatments with either heterogeneous or homogeneous Zn supply and in a treatment with no Zn added to the substrate. • Prayon exhibited enhanced above- and below-ground biomass production, and zincophilic root foraging patterns in response to heterogeneously distributed Zn. The root placement pattern suggested that T. caerulescens may discriminate between patches with contrasting Zn concentrations and produce more roots in patches with higher Zn concentrations. Bradford Dale did not show these responses. • The T. caerulescens ecotypes may differ in their Zn requirements or may have experienced selection for genetic differences that affect their ability to respond to Zn heterogeneity. Such differences will be important factors in the successful phytoremediation of contaminated soils.

Nitrogen uptake : Apparent pattern during old field succession in Southeastern U.S.

Nitrogen uptake from applied nutrient solutions was evaluated in two old fields, in a pine plantation, and in a hardwood stand, to test the idea that plant communities become more efficient trappers and retainers of plant nutrients during succession. Uptake was estimated as the difference between nutrient concentrations in water collected from beneath soil profiles with and without roots by lysimeters within each successional stage. Results suggest that nitrate uptake decreased while ammonia uptake increased with succession. This apparent shift from a nitrate to an ammonia nitrogen economy during succession has been reported by other workers and is evolutionarily significant as an energy, nitrogen, and cation saving mechanism.

The Children's Attributional Style Interview: developmental tests of cognitive diathesis-stress theories of depression.

This paper presents an initial assessment of the Children's Attributional Style Interview (CASI), a newly designed measure for assessing attributional style in young children (age 5 and up). The CASI was used to conduct prospective tests of the reformulated helplessness and the integrated hopelessness/self-esteem theories of depression in a sample of 147 5-10-year-old children. For comparison, the same tests were also conducted with the Children's Attributional Style Questionnaire-Revised, a commonly used measure for assessing attributional style in older children (age 8 and up). The CASI evidenced support of the reformulated helplessness theory and partial support of the integrated hopelessness/self-esteem theory. The CASI also demonstrated good internal consistency. Thus, our findings provide initial support for the CASI as a methodologically sound measure of attributional style for children as young as 5 years old. Although preliminary, our findings also suggest possible developmental differences in how attributional style interacts with self-esteem and negative life stress. The CASI should prove to be a useful tool in furthering the understanding of the origins and development of attributional style in childhood, as well as its contribution to the understanding of the development and prevention of depressive symptomatology in children.

Shear bond strength of four filled dentin bonding systems.

This study compared the shear bond strength of four filled dentin bonding agents (Prime & Bond NT, One Coat Bond, OptiBond Solo, PermaQuik1) to a conventional unfilled Dentin Bonding agent (3M Scotchbond Multipurpose Plus). A column of composite resin (Herculite XRV Restorative Resin) was bonded to human dentin using the five dentin-bonding systems following the manufacturers' directions. The specimens were thermocycled 1000 cycles from 6 to 60 degrees C. Each specimen was tested on an MTS machine in shear-to-failure. The data were subjected to One-Factor ANOVA and Newman-Kuels post-hoc tests. Statistical analysis revealed that One Coat Bond had significantly greater shear bond strength than all other materials tested.

Rehabilitation of the painful upper extremity.

Therapy for the painful upper extremity is a challenge. This article focuses on various assessment tools and techniques that are reflective of the painful status. The author reviews several research articles that discuss validating treatment options and outlines rehabilitation for the painful upper extremity as it relates to peripheral nerve irritation and compression.

Accessibility changes across the mouse Igh-V locus during B cell development.

During their development, B and T lymphocytes are thought to undergo several cycles of chromatin remodeling at their antigen receptor loci that serve to regulate access of a common V(D)J recombinase to particular gene segments. We used germ-line transcription and susceptibility to DNasel as markers to examine tissue and stage-specific changes in chromatin structure surrounding genes of the VHJ558, VH10, and VHS107 families, whose members are located at discreet subregions of the locus. Germ-line VH transcripts from all three families were detectable at pro- and pre-B cell stages. Transcripts from the VH10 and VHS107 families, but not VHJ558, remained detectable at the immature and mature B cell stages. Unexpectedly, none of the germ-line VH loci examined were markedly nuclease sensitive, regardless of cell type or transcriptional activity. A modest degree of nuclease sensitivity was noted at the VHJ558 loci of pro-B and pre-B cells, however. Our data suggest that the entire Igh-V locus becomes accessible at early B cell stages, and returns thereafter to an inaccessible state. However, the timing of these accessibility changes does not occur uniformly across the VH array. These results imply that multiple long-range elements are involved in targeting VH genes for rearrangement.

Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.

Nedd4 is a member of a growing family of ubiquitin-protein ligases which consist of a lipid-binding domain, two to four WW domains and a C-terminal ubiquitin-protein ligase domain. The Nedd4 mRNA levels are developmentally regulated and Nedd4 protein is highly expressed in many mouse embryonic tissues. In this study we have used a far-Western screen to identify embryonic proteins that interact with the WW domains in mouse Nedd4. We report here identification of eight Nedd4 WW-domain-interacting proteins from mouse embryonic cDNA expression libraries. Two of the proteins are novel, while two have been identified previously as ligands for a WW domain. All of these proteins contain one or more PY motifs. In seven of the eight proteins, these PY motifs are necessary for their interaction with the WW domains of Nedd4. Using site-directed mutagenesis, and by using individual WW domains of Nedd4 as probes for far-Western analysis, we show that the three WW domains in Nedd4 interact with varying affinities with the PY motifs present in various Nedd4-binding proteins. These results provide evidence that Nedd4 can potentially interact with multiple proteins, possibly simultaneously, through its WW domains.

Complex conserved organization of the mammalian leukemia inhibitory factor gene: regulated expression of intracellular and extracellular cytokines.

Leukemia inhibitory factor (LIF) is a member of the IL-6 family of pleiotropic cytokines, which are extensively involved in modulating hematopoiesis and immunity. We have undertaken a detailed analysis of LIF genomic organization and gene transcription and investigated the proteins expressed from alternate transcripts. Previously unidentified LIF transcripts, containing alternate first exons spliced onto common second and third exons, were cloned from murine embryonic stem cells, human embryonal carcinoma cells, and primary porcine fibroblasts. Based on sequence homology and position within the genomic sequence, this confirmed the existence of the LIF-M transcript in species other than the mouse and identified a new class of transcript, designated LIF-T. Thus, a complex genomic organization of the LIF gene, conserved among eutherian mammals, results in the expression of three LIF transcripts (LIF-D, LIF-M, and LIF-T) differentially expressed from alternate promoters. The first exon of the LIF-T transcript contained no in-frame AUG, causing translation to initiate downstream of the secretory signal sequence at the first AUG in exon two, producing a truncated LIF protein that was localized within the cell. Enforced secretion of this protein demonstrated that it could act as a LIF receptor agonist. Regulated expression of biologically active intracellular and extracellular LIF cytokine could thus provide alternate mechanisms for the modulation of hematopoiesis and immune system function.

Human germ cell tumor cell lines express novel leukemia inhibitory factor transcripts encoding differentially localized proteins.

The polyfunctional cytokine leukemia inhibitory factor (LIF) has been implicated in the maintenance of many stem and progenitor cell populations and as an autocrine growth factor for many tumor cell populations, including germ cell tumors. Studies of LIF transcript expression in germ cell tumor cell lines identified two novel human LIF transcripts, hLIF-M and hLIF-T, containing noncoding alternate first exons that are conserved among all reported LIF genes. Embryonal carcinoma (EC) cell lines expressed these transcripts at consistent levels and hLIF-M was generally the predominant LIF transcript in these cells. This expression pattern was characteristic of EC cells since variable independently regulated expression of these transcripts was evident in other cell lines. Overexpression analysis demonstrated that each alternate hLIF transcript generated different levels of extracellular LIF activity as a consequence of the translation of distinct but partially overlapping sets of proteins. Secreted LIF proteins translated from alternate initiation codons were expressed from the hLIF-D and hLIF-M transcripts. Intracellular, potentially cell-autonomous, proteins were encoded by the hLIF-M and hLIF-T transcripts. Since EC cell lines also expressed LIF receptor transcripts, the novel LIF transcription profiles and proteins identified here suggest a role for autocrine and/or cell-autonomous LIF signaling during germ cell tumorigenesis.