Polarization Measurements During Electron Cyclotron Heating Experiments in the DIII-D Tokamak

The polarization of the launched electron cyclotron wave has been optimized for coupling to the X-mode by adjusting the inclination of grooved mirrors located in two consecutive mitre bends of the waveguide. The unwanted O-mode component of the launched beam can be positively identified by the difference in the power deposition profiles between X-mode and O-mode. The optimal polarization for X-mode launch is in good agreement with theoretical expectations

Polarization, propagation, and deposition measurements during ECCD experiments on the DIII-D tokamak

The power deposition profiles for different poloidal and toroidal launch angles have been determined by modulating the ECH power and measuring the electron temperature response. The peak of the measured power density follows the poloidal steering of the ECH launcher, and perpendicular launch gives a narrower deposition profile than does oblique (current drive) launch. The difference in wave refraction between X-mode and O-mode allows positive identification of an unwanted O-mode component of the launched beam

Energetic ion transport by microturbulence is insignificant in tokamaks

Energetic ion transport due to microturbulence is investigated in magnetohydrodynamic-quiescent plasmas by way of neutral beam injection in the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)]. A range of on-axis and off-axis beam injection scenarios are employed to vary relevant parameters such as the character of the background microturbulence and the value of Eb/Te , where Eb is the energetic ion energy and Te the electron temperature. In all cases, it is found that any transport enhancement due to microturbulence is too small to observe experimentally. These transport effects are modeled using numerical and analytic expectations that calculate the energetic ion diffusivity due to microturbulence. It is determined that energetic ion transport due to coherent fluctuations (e.g., Alfvén eigenmodes) is a considerably larger effect and should therefore be considered more important for ITER.United States. Dept. of Energy (DE-FC02-04ER54698)United States. Dept. of Energy (DE-FC02-99ER54512)United States. Dept. of Energy (DE-FG03-97ER54415)United States. Dept. of Energy (DE-FG02-07ER54917)United States. Dept. of Energy (DE-AC02-09CH11466)United States. Dept. of Energy (SC-G903402)United States. Dept. of Energy (DE-FG02-08ER54984)United States. Dept. of Energy ( DE-AC52-07NA27344)United States. Dept. of Energy ( DE-FG02-89ER53296)United States. Dept. of Energy (DE-FG02-08ER54999)United States. Dept. of Energy (DE-AC05-00OR22725

The potent and broadly neutralizing human dengue virus-specific monoclonal antibody 1C19 reveals a unique cross-reactive epitope on the bc loop of domain II of the envelope protein

ABSTRACTFollowing natural dengue virus (DENV) infection, humans produce some antibodies that recognize only the serotype of infection (type specific) and others that cross-react with all four serotypes (cross-reactive). Recent studies with human antibodies indicate that type-specific antibodies at high concentrations are often strongly neutralizing in vitro and protective in animal models. In general, cross-reactive antibodies are poorly neutralizing and can enhance the ability of DENV to infect Fc receptor-bearing cells under some conditions. Type-specific antibodies at low concentrations also may enhance infection. There is an urgent need to determine whether there are conserved antigenic sites that can be recognized by cross-reactive potently neutralizing antibodies. Here, we describe the isolation of a large panel of naturally occurring human monoclonal antibodies (MAbs) directed to the DENV domain II fusion loop (FL) envelope protein region from subjects following vaccination or natural infection. Most of the FL-specific antibodies exhibited a conventional phenotype, characterized by low-potency neutralizing function and antibody-dependent enhancing activity. One clone, however, recognized the bc loop of domain II adjacent to the FL and exhibited a unique phenotype of ultrahigh potency, neutralizing all four serotypes better than any other previously described MAb recognizing this region. This antibody not only neutralized DENV effectively but also competed for binding against the more prevalent poor-quality antibodies whose binding was focused on the FL. The 1C19 human antibody could be a promising component of a preventative or therapeutic intervention. Furthermore, the unique epitope revealed by 1C19 suggests a focus for rational vaccine design based on novel immunogens presenting cross-reactive neutralizing determinants.IMPORTANCEWith no effective vaccine available, the incidence of dengue virus (DENV) infections worldwide continues to rise, with more than 390 million infections estimated to occur each year. Due to the unique roles that antibodies are postulated to play in the pathogenesis of DENV infection and disease, there is consensus that a successful DENV vaccine must protect against all four serotypes. If conserved epitopes recognized by naturally occurring potently cross-neutralizing human antibodies could be identified, monovalent subunit vaccine preparations might be developed. We characterized 30 DENV cross-neutralizing human monoclonal antibodies (MAbs) and identified one (1C19) that recognized a novel conserved site, known as the bc loop. This antibody has several desirable features, as it neutralizes DENV effectively and competes for binding against the more common low-potency fusion loop (FL) antibodies, which are believed to contribute to antibody-mediated disease. To our knowledge, this is the first description of a potent serotype cross-neutralizing human antibody to DENV

Application of ECH to the Study of Transport in ITER Baseline Scenario-like Discharges in DIII-D

Recent DIII-D experiments in the ITER Baseline Scenario (IBS) have shown strong increases in fluctuations and correlated reduction of confinement associated with entering the electron-heating-dominated regime with strong electron cyclotron heating (ECH). The addition of 3.2 MW of 110 GHz EC power deposited at ρ~0.42 to IBS discharges with ~3 MW of neutral beam injection causes large increases in low-k and medium-k turbulent density fluctuations observed with Doppler backscatter (DBS), beam emission spectroscopy (BES) and phase-contrast imaging (PCI) diagnostics, correlated with decreases in the energy, particle, and momentum confinement times. Power balance calculations show the electron heat diffusivity χ[subscript e] increases significantly in the mid-radius region 0.4<ρ<0.8, which is roughly the same region where the DBS and BES diagnostics show the increases in turbulent density fluctuations. Confinement of angular momentum is also reduced during ECH. Studies with the TGYRO transport solver show that the model of turbulent transport embodied in the TGLF code quantitatively reproduces the measured transport in both the neutral beam (NB)-only and in the NB plus EC cases. A simple model of the decrease in toroidal rotation with EC power is set forth, which exhibits a bifurcation in the rotational state of the discharge.United States. Dept. of Energy (DE-FC02-04ER54698)United States. Dept. of Energy (DE-FC02-08ER54966)United States. Dept. of Energy (DE-AC03-09CH11466)United States. Dept. of Energy (DE-FG02-04ER54235)United States. Dept. of Energy (DE-FG0289ER53296)United States. Dept. of Energy (DE-FG02-08ER54999)United States. Dept. of Energy (DE-FG02-08ER54984)United States. Dept. of Energy (DE-FG02-04ER54461

Suppression of Tearing Modes by Means of Localized Electron Cyclotron Current Drive in the Diii-D Tokamak

The onset of tearing modes and the resulting negative effects on plasma performance set significant limits on the operational domain of tokamaks. Modes with toroidal mode number (n) larger than two cause only a minor reduction in energy confinement (&lt;10%). Modes which have a dominant poloidal mode number (m) of three and n=2 lead to a significant reduction in confinement (&lt;30%) at fixed power. The plasma pressure {beta} (normalized to the magnetic field pressure) can be raised further, albeit with very small incremental confinement. Pushing to higher {beta} often destabilizes the m=2/n=1 tearing mode which can lock to the wall and lead to a complete and rapid disruption of the plasma with potentially serious consequences for the tokamak. The {beta} values at which these modes usually appear in conventional tokamak discharges are well below the limits calculated using ideal MHD theory. Therefore, the tearing modes can set effective upper limits on energy confinement and pressure. Significant progress has been made in stabilizing these modes by local current generation using electron cyclotron waves. The tearing mode is essentially a deficit in current flowing helically, resonant with the spatial structure of the local magnetic field. This forms an ''island'' where the magnetic flux is no longer monotonic. It was predicted theoretically [1,2] that replacement of this ''missing'' current would return the plasma to the state prior to the instability. Experiments on the ASDEX-Upgrade [3], JT-60U [4], and DIII-D [5] tokamaks have demonstrated stabilization of m=3/n=2 modes using electron cyclotron current drive (ECCD) to replace the current in the island. Following these initial experiments, recent work on the DIII-D tokamak has demonstrated two significant advances in application of this technique--extending the operational domain stable to m=3/n=2 modes to higher {beta} and the first suppression of the more dangerous m=2/n=1 mode

2013 Review and Update of the Genetic Counseling Practice Based Competencies by a Task Force of the Accreditation Council for Genetic Counseling

The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non‐clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors’ roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre‐defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force’s work, key changes and the 2013 PBCs are presented herein.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147172/1/jgc40868.pd

Generation of a non-small cell lung cancer transcriptome microarray

<p>Abstract</p> <p>Background</p> <p>Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. At present no reliable biomarkers are available to guide the management of this condition. Microarray technology may allow appropriate biomarkers to be identified but present platforms are lacking disease focus and are thus likely to miss potentially vital information contained in patient tissue samples.</p> <p>Methods</p> <p>A combination of large-scale in-house sequencing, gene expression profiling and public sequence and gene expression data mining were used to characterise the transcriptome of NSCLC and the data used to generate a disease-focused microarray – the Lung Cancer DSA research tool.</p> <p>Results</p> <p>Built on the Affymetrix GeneChip platform, the Lung Cancer DSA research tool allows for interrogation of ~60,000 transcripts relevant to Lung Cancer, tens of thousands of which are unavailable on leading commercial microarrays.</p> <p>Conclusion</p> <p>We have developed the first high-density disease specific transcriptome microarray. We present the array design process and the results of experiments carried out to demonstrate the array's utility. This approach serves as a template for the development of other disease transcriptome microarrays, including non-neoplastic diseases.</p