High Energy Electron Confinement in a Magnetic Cusp Configuration

We report experimental results validating the concept that plasma confinement is enhanced in a magnetic cusp configuration when beta (plasma pressure/magnetic field pressure) is order of unity. This enhancement is required for a fusion power reactor based on cusp confinement to be feasible. The magnetic cusp configuration possesses a critical advantage: the plasma is stable to large scale perturbations. However, early work indicated that plasma loss rates in a reactor based on a cusp configuration were too large for net power production. Grad and others theorized that at high beta a sharp boundary would form between the plasma and the magnetic field, leading to substantially smaller loss rates. The current experiment validates this theoretical conjecture for the first time and represents critical progress toward the Polywell fusion concept which combines a high beta cusp configuration with an electrostatic fusion for a compact, economical, power-producing nuclear fusion reactor.Comment: 12 pages, figures included. 5 movies in Ancillary file

Striatal Acetylcholine-Dopamine Imbalance in Parkinson Disease:In Vivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET-Informed Correlational Tractography

Previous studies of animal models of Parkinson disease (PD) suggest an imbalance between striatal acetylcholine and dopamine, although other studies have questioned this. To our knowledge, there are no previous in vivo neuroimaging studies examining striatal acetylcholine-dopamine imbalance in PD patients. Using cholinergic and dopaminergic PET (F-18-fluoroethoxybenzovesamicol [F-18-FEOBV] and C-11-dihydrotetrabenazine [C-11-DTBZ], respectively) and correlational tractography, our aim was to investigate the acetylcholine-dopamine interaction at 2 levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 +/- 6.3 y, disease duration, 5.8 +/- 3.6 y; Hoehn and Yahr stage, 2.2 +/- 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 +/- 8.6 y). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal C-11-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy [QA], a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with the striatal F-18-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for C-11-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike C-11-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected hemisphere showed a negative correlation with a striatal cluster of F-18-FEOBV DVR in PD subjects (corrected P = 0.039). We also found that the mean F-18-FEOBV DVR within this cluster was higher in the PD group than in the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase in bradykinesia ratings associated with increased acetylcholine-dopamine imbalance in the most affected hemisphere (r = 0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal acetylcholine-dopamine imbalance in early PD and may provide an avenue for testing in vivo effects of therapeutic strategies aimed at restoring striatal acetylcholine-dopamine balance in PD

On Random Field Induced Ordering in the Classical XY Model

Consider the classical XY model in a weak random external field pointing along the $Y$ axis with strength $\epsilon$. We study the behavior of this model as the range of the interaction is varied. We prove that in any dimension $d \geq 2$ and for all $\epsilon$ sufficiently small, there is a range $L=L(\epsilon)$ so that whenever the inverse temperature $\beta$ is larger than some $\beta(\epsilon)$, there is strong residual ordering along the $X$ direction.Comment: 30 page

Set1/COMPASS repels heterochromatin invasion at euchromatic sites by disrupting Suv39/Clr4 activity and nucleosome stability.

Protection of euchromatin from invasion by gene-repressive heterochromatin is critical for cellular health and viability. In addition to constitutive loci such as pericentromeres and subtelomeres, heterochromatin can be found interspersed in gene-rich euchromatin, where it regulates gene expression pertinent to cell fate. While heterochromatin and euchromatin are globally poised for mutual antagonism, the mechanisms underlying precise spatial encoding of heterochromatin containment within euchromatic sites remain opaque. We investigated ectopic heterochromatin invasion by manipulating the fission yeast mating type locus boundary using a single-cell spreading reporter system. We found that heterochromatin repulsion is locally encoded by Set1/COMPASS on certain actively transcribed genes and that this protective role is most prominent at heterochromatin islands, small domains interspersed in euchromatin that regulate cell fate specifiers. Sensitivity to invasion by heterochromatin, surprisingly, is not dependent on Set1 altering overall gene expression levels. Rather, the gene-protective effect is strictly dependent on Set1's catalytic activity. H3K4 methylation, the Set1 product, antagonizes spreading in two ways: directly inhibiting catalysis by Suv39/Clr4 and locally disrupting nucleosome stability. Taken together, these results describe a mechanism for spatial encoding of euchromatic signals that repel heterochromatin invasion

The Effects of Cannabidiol Supplementation on Measures of Performance and Fatigue Following Eccentric Exercise

Following intense exercise, there is a period of time where performance is decreased. This period of reduced performance is characterized by several factors including myofibrillar disruption, reduced range-of-motion, inflammation, and an influx of enzymes and proteins. Cannabidiol (CBD) has been marketed as a recovery supplement capable of reducing markers of fatigue and inflammation following exercise, yet this claim has not been investigated. PURPOSE: The purpose of this study was to determine if CBD supplementation limits fatigue and expedites a return to performance following intense eccentric exercise. METHODS: A double-blind, crossover design with repeated measures was used. Twenty-four NCAA female athletes (age = 21.2 ± 1.8 yrs., height = 166.4 ± 8 cm, weight = 64.9 ± 9.1 kg) were randomized to either receive 5 mg/kg of CBD in pill form (Cannabidiol Life, Longwood, FL) or a matched weight placebo. Treatments were consumed two hours prior to, immediately following, and ten hours following muscle damage sessions. All participants consumed both treatments, with each separated by approximately 28 days to control for the menstrual cycle. To induce muscle damage, participants completed 10 sets of 10 repetitions of unilateral eccentric leg extension at 60°/sec on an isokinetic dynamometer (Biodex Medical Systems Inc., Shirley, NY). Concentrations of a blood marker indicative of muscle damage (myoglobin), in addition to measures of fatigue (visual analogue fatigue scale [VAFS]) and performance (vertical jump, peak dynamic knee extensor torque at 60, 180, and 300°/sec, and peak isometric knee extensor torque), were collected before and 4, 24, and 48 hours following muscle damaging sessions. A repeated measures MANOVA was conducted to analyze the performance measures, and separate repeated measures ANOVAs were conducted to analyze myoglobin concentrations and results from the VAFS with a significance level of 0.05. RESULTS: A significant increase (p = 0.002) in myoglobin levels was observed for both treatments 4 hours following the muscle damaging session but no significant differences (p \u3e 0.05) were observed between the CBD and placebo groups at any of the 4 measured time points. Peak torque at 60°/sec (p = 0.001) and peak isometric torque (p = 0.02) were significantly lower 24 hours following muscle damage, but none of the 5 measured performance variables were significantly different (p \u3e 0.05 for all) between the CBD and placebo treatment at any time point. Subjective fatigue as measured by the VAFS was not significantly different (p \u3e 0.05) between the CBD and placebo treatments at any measured time point. CONCLUSION: Cannabidiol supplementation was unable to reduce fatigue and restore performance when compared to a placebo in well-trained female participants. It does not appear that CBD supplementation is of beneficial use as a recovery supplement following intense exercise in athletes

Coupled measurements of δ18O and δD of hydration water and salinity of fluid inclusions in gypsum from the Messinian Yesares Member, Sorbas Basin (SE Spain)

Financial support was provided by Clare College Geological Research Fund to N.P. Evans. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement n. 339694 (Water Isotopes of Hydrated Minerals) to D.A. Hodell.We studied one cycle (Cycle 6) of gypsum-marl deposition from the Messinian Yesares Member in Sorbas Basin, Spain. The objective was to reconstruct the changing environment of deposition and its relation to astronomically-forced climate change. The δ18O and δD of gypsum hydration water (CaSO4 • 2H2O) and salinity of fluid inclusions were measured in the same samples to test if they record the composition of the mother fluid from which gypsum was precipitated. Water isotopes are highly correlated with fluid inclusion salinity suggesting the hydration water has not exchanged after formation. The relatively low water isotope values and fluid inclusion salinities indicate a significant influence of meteoric water, whereas δ34S, δ18OSO4 and 87Sr/86Sr support a dominant marine origin for the gypsum deposits. The discrepancy between water and elemental isotope signatures can be reconciled if meteoric water dissolved previously deposited marine sulfates supplying calcium and sulfate ions to the basin which maintained gypsum saturation. This recycling process accounts for the marine δ34S, δ18OSO4 and 87Sr/86Sr signatures, whereas the low δ18O and δD values of gypsum hydration water and fluid inclusion salinities reflect the influence of freshwater. The cyclic deposition of gypsum and marl in the Yesares Member has previously been interpreted to reflect changing climate related to Earth's precession cycle. We demonstrate that the δ18O, δD and salinity of the parent brine increased from low values at the base of the cycle to a maximum in the massive gypsum palisade, and decreased again to lower values in the supercones at the top of the cycle. This pattern, together with changes in mineralogy (calcite-dolomite-gypsum), is consistent with a precession-driven change in climate with wettest conditions (summer insolation maxima) associated with the base of the calcium carbonate marls and driest conditions (summer insolation minima) during formation of the gypsum palisade.Publisher PDFPeer reviewe

Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease:In Vivo Neuroimaging Study of C-11-DTBZ PET Combined with Correlational Tractography

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. C-11-dihydrotetrabenazine (C-11-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by C-11-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on C-11-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 +/- 6.2 y; disease duration, 6.4 +/- 4.0 y; Hoehn and Yahr stage, 2.1 +/- 0.6; Movement Disorder Society [MDS]-revised Unified Parkinson Disease Rating Scale [UPDRS] [I-III] total score, 43.4 +/- 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 +/- 10.3 y). C-11-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal C-11-DTBZ data using the DS! Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal C-11-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = 0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of earlyor even prodromal-stage PD

Multiwavelength Variations of 3C 454.3 during the November 2010 to January 2011 Outburst

We present multiwavelength data of the blazar 3C 454.3 obtained during an extremely bright outburst from November 2010 through January 2011. These include flux density measurements with the Herschel Space Observatory at five submillimeter-wave and far-infrared bands, the Fermi Large Area Telescope at gamma-ray energies, Swift at X-ray, ultraviolet (UV), and optical frequencies, and the Submillimeter Array at 1.3 mm. From this dataset, we form a series of 52 spectral energy distributions (SEDs) spanning nearly two months that are unprecedented in time coverage and breadth of frequency. Discrete correlation anlaysis of the millimeter, far-infrared, and gamma-ray light curves show that the variations were essentially simultaneous, indicative of co-spatiality of the emission, at these wavebands. In contrast, differences in short-term fluctuations at various wavelengths imply the presence of inhomegeneities in physical conditions across the source. We locate the site of the outburst in the parsec-scale core, whose flux density as measured on 7 mm Very Long Baseline Array images increased by 70 percent during the first five weeks of the outburst. Based on these considerations and guided by the SEDs, we propose a model in which turbulent plasma crosses a conical standing shock in the parsec-scale region of the jet. Here, the high-energy emission in the model is produced by inverse Compton scattering of seed photons supplied by either nonthermal radiation from a Mach disk, thermal emission from hot dust, or (for X-rays) synchrotron radiation from plasma that crosses the standing shock. For the two dates on which we fitted the model SED to the data, the model corresponds very well to the observations at all bands except at X-ray energies, where the spectrum is flatter than observed.Comment: Accepted for publication in Astrophysical Journal. 82 pages, 13 figure

Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells

The insulin/IGF-1 (insulin-like growth factor 1)-activated protein kinase Akt (also known as protein kinase B) phosphorylates Ser(487) in the ‘ST loop’ (serine/threonine-rich loop) within the C-terminal domain of AMPK-α1 (AMP-activated protein kinase-α1), leading to inhibition of phosphorylation by upstream kinases at the activating site, Thr(172). Surprisingly, the equivalent site on AMPK-α2, Ser(491), is not an Akt target and is modified instead by autophosphorylation. Stimulation of HEK (human embryonic kidney)-293 cells with IGF-1 caused reduced subsequent Thr(172) phosphorylation and activation of AMPK-α1 in response to the activator A769662 and the Ca(2+) ionophore A23187, effects we show to be dependent on Akt activation and Ser(487) phosphorylation. Consistent with this, in three PTEN (phosphatase and tensin homologue deleted on chromosome 10)-null tumour cell lines (in which the lipid phosphatase PTEN that normally restrains the Akt pathway is absent and Akt is thus hyperactivated), AMPK was resistant to activation by A769662. However, full AMPK activation could be restored by pharmacological inhibition of Akt, or by re-expression of active PTEN. We also show that inhibition of Thr(172) phosphorylation is due to interaction of the phosphorylated ST loop with basic side chains within the αC-helix of the kinase domain. Our findings reveal that a previously unrecognized effect of hyperactivation of Akt in tumour cells is to restrain activation of the LKB1 (liver kinase B1)–AMPK pathway, which would otherwise inhibit cell growth and proliferation