Constance mirror program: Progress and plans

The current state of the mechanics of the Constance II experiment, the physics results gathered, the motivation background, and future plans for the Constance II experiment are reviewed. Several improvements have been made and several experimental investigations have been completed. These include the construction/installation/testing of: (1) liquid-nitrogen cooled, Ioffe bars installed, (2) a diverter coil (3) the 100 kW ICRF generator, (4) the data acquisition system, and (5) the optimum hot-iron operation of the machine with Titanium and pulsed-gas plasma guns. Measurements were made of the density, temperature, and radius of the plasma. Ion-cyclotron fluctuations were observed, their bandwidth measured, and data collected demonstrating resonance heating. New X-ray diagnostics were designed and purchased, and progress on the Thomson scattering was made. Finally, a new hot cathode gun was designed and constructed

Picosecond Timing Resolution Detection of Gamma Photons Utilizing Microchannel-plate Detectors: Experimental Tests of Quantum Nonlocality and Photon Localization

The concept and subsequent experimental verification of the proportionality between pulse amplitude and detector transit time for microchannel plate detectors is presented. This discovery has led to considerable improvement in the overall timing resolution for detection of high energy gamma photons. Utilizing a 22Na positron source, a full width half maximum (FWHM) timing resolution of 138 ps has been achieved. This FWHM includes detector transit-time spread for both chevron-stack type detectors, timing spread due to uncertainties in annihilation location, all electronic uncertainty, and any remaining quantum mechanical uncertainty. The first measurement of the minimum quantum uncertainty in the time interval between detection of the two annihilation photons is reported. The experimental results give strong evidence against instantaneous spatial-localization of gamma photons due to measurement-induced nonlocal quantum wave-function collapse. The experimental results are also the first that imply momentum is conserved only after the quantum uncertainty in time has elapsed [H. Yukawa, Proc. Phys. -Math. Soc. Japan, 17, 48 (1935)].Comment: As published in Meas. Sci. Technol. 15 (2004) 1799-181

High-Voltage Variable Resistor for Ion Energy Spectroscopy

A high-voltage variable resistor was designed, built, and implemented to modify an ion-energy spectrometer for the study of ion-atom collisions in which the projectiles change charge. The resistor is remotely switchable from 0 to 2050 MΩ and has a voltage rating of 200 kV. The design criteria and the electrical and mechanical details of the apparatus are discussed. The design and construction of an ancillary device, comprising two precision resistive-divider voltmeters, are also discussed

Longitudinal evaluation, acceptability and long-term retention of knowledge on a horizontally integrated organic and functional systems course

Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge

Structural basis for Cas9 off-target activity

The target DNA specificity of the CRISPR-associated genome editor nuclease Cas9 is determined by complementarity to a 20-nucleotide segment in its guide RNA. However, Cas9 can bind and cleave partially complementary off-target sequences, which raises safety concerns for its use in clinical applications. Here, we report crystallographic structures of Cas9 bound to bona fide off-target substrates, revealing that off-target binding is enabled by a range of noncanonical base-pairing interactions within the guide:off-target heteroduplex. Off-target substrates containing single-nucleotide deletions relative to the guide RNA are accommodated by base skipping or multiple noncanonical base pairs rather than RNA bulge formation. Finally, PAM-distal mismatches result in duplex unpairing and induce a conformational change in the Cas9 REC lobe that perturbs its conformational activation. Together, these insights provide a structural rationale for the off-target activity of Cas9 and contribute to the improved rational design of guide RNAs and off-target prediction algorithms

Inference of Experimental Radial Impurity Transport on Alcator C-Mod: Bayesian Parameter Estimation and Model Selection

We present a fully Bayesian approach for the inference of radial profiles of impurity transport coefficients and compare its results to neoclassical, gyrofluid and gyrokinetic modeling. Using nested sampling, the Bayesian Impurity Transport InferencE (BITE) framework can handle complex parameter spaces with multiple possible solutions, offering great advantages in interpretative power and reliability with respect to previously demonstrated methods. BITE employs a forward model based on the pySTRAHL package, built on the success of the well-known STRAHL code [Dux, IPP Report, 2004], to simulate impurity transport in magnetically-confined plasmas. In this paper, we focus on calcium (Ca, Z=20) Laser Blow-Off injections into Alcator C-Mod plasmas. Multiple Ca atomic lines are diagnosed via high-resolution X-ray Imaging Crystal Spectroscopy and Vacuum Ultra-Violet measurements. We analyze a sawtoothing I-mode discharge for which neoclassical and turbulent (quasilinear and nonlinear) predictions are also obtained. We find good agreement in diffusion across the entire radial extent, while turbulent convection and density profile peaking are estimated to be larger in experiment than suggested by theory. Efforts and challenges associated with the inference of experimental pedestal impurity transport are discussed.Comment: 38 pages, 19 figures, submitted for publication in Nuclear Fusio

Operation of Alcator C-Mod with high-Z plasma facing components and implications

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Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome