A Planetary Companion to gamma Cephei A

We report on the detection of a planetary companion in orbit around the primary star of the binary system $\gamma$ Cephei. High precision radial velocity measurements using 4 independent data sets spanning the time interval 1981--2002 reveal long-lived residual radial velocity variations superimposed on the binary orbit that are coherent in phase and amplitude with a period or 2.48 years (906 days) and a semi-amplitude of 27.5 m s$^{-1}$. We performed a careful analysis of our Ca II H & K S-index measurements, spectral line bisectors, and {\it Hipparcos} photometry. We found no significant variations in these quantities with the 906-d period. We also re-analyzed the Ca II $\lambda$8662 {\AA} measurements of Walker et al. (1992) which showed possible periodic variations with the ``planet'' period when first published. This analysis shows that periodic Ca II equivalent width variations were only present during 1986.5 -- 1992 and absent during 1981--1986.5. Furthermore, a refined period for the Ca II $\lambda$8662 {\AA} variations is 2.14 yrs, significantly less than residual radial velocity period. The most likely explanation of the residual radial velocity variations is a planetary mass companion with $M$ sin $i$ = 1.7 $M_{Jupiter}$ and an orbital semi-major axis of $a_2$ $=$ 2.13 AU. This supports the planet hypothesis for the residual radial velocity variations for $\gamma$ Cep first suggested by Walker et al. (1992). With an estimated binary orbital period of 57 years $\gamma$ Cep is the shortest period binary system in which an extrasolar planet has been found. This system may provide insights into the relationship between planetary and binary star formation.Comment: 19 pages, 15 figures, accepted in Ap. J. Includes additional data and improved orbital solutio

The Extinction and Distance of Maffei 1

We have obtained low- and high-resolution spectra of the core of the highly-reddened elliptical galaxy Maffei 1. From these data, we have obtained the first measurement of the Mg2 index, and have measured the velocity dispersion and radial velocity with improved accuracy. To evaluate the extinction, a correlation between the Mg2 index and effective V-I colour has been established for elliptical galaxies. Using a new method for correcting for effective wavelength shifts, we find A_V = 4.67 +/- 0.19 mag, which is lower by 0.4 mag than previously thought. To establish the distance, the Fundamental Plane for elliptical galaxies has been constructed in I. The velocity dispersion of Maffei 1, measured to be 186.8 +/- 7.4 km/s, in combination with modern wide-field photometry in I, leads to a distance of 2.92 +/- 0.37 Mpc. The Dn-sigma relation, which is independently calibrated, gives 3.08 +/- 0.85 Mpc and 3.23 +/- 0.67 Mpc from photometry in B and K`, respectively. The weighted mean of the three estimates is 3.01 +/- 0.30 Mpc. The distance and luminosity make Maffei 1 the nearest giant elliptical galaxy. The radial velocity of Maffei 1 is +66.4 +/- 5.0 km/s, significantly higher than the accepted value of -10 km/s. The Hubble distance corresponding to the mean velocity of Maffei 1, Maffei 2 and IC342 is 3.5 Mpc. Thus, it is unlikely that Maffei 1 has had any influence on Local Group dynamics

Optimal binary gratings for multi-wavelength magneto-optical traps

Grating magneto-optical traps are an enabling quantum technology for portable metrological devices with ultracold atoms. However, beam diffraction efficiency and angle are affected by wavelength, creating a single-optic design challenge for laser cooling in two stages at two distinct wavelengths - as commonly used for loading e.g. Sr or Yb atoms into optical lattice or tweezer clocks. Here, we optically characterize a wide variety of binary gratings at different wavelengths to find a simple empirical fit to experimental grating diffraction efficiency data in terms of dimensionless etch depth and period for various duty cycles. The model avoids complex 3D light-grating surface calculations, yet still yields results accurate to a few percent across a broad range of parameters. Gratings optimized for two (or more) wavelengths can now be designed in an informed manner suitable for a wide class of atomic species enabling advanced quantum technologies.Comment: 11 pages, 3 figures, 2 tables. See also 4-page supplementary documen

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial

Background The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. Methods We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m2 or more (or ≥28 kg/m2 with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+—a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. Findings Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6–2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34–2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96–2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31–2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI −129 to 195) for POWeR+F and –£25 (−268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. Interpretation Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year

Near Resonant Spatial Images of Confined Bose-Einstein Condensates in the '4D' Magnetic Bottle

We present quantitative measurements of the spatial density profile of Bose-Einstein condensates of sodium atoms confined in a new '4D' magnetic bottle. The condensates are imaged in transmission with near resonant laser light. We demonstrate that the Thomas-Fermi surface of a condensate can be determined to better than 1%. More generally, we obtain excellent agreement with mean-field theory. We conclude that precision measurements of atomic scattering lengths and interactions between phase separated cold atoms in a harmonic trap can be measured with high precision using this method.Comment: 15 pages, 3 figures. Submitted 10/30/97, accepted for publication in Phys. Rev. A Rapid Com

Interference effects in the photorecombination of argonlike Sc3+ ions: Storage-ring experiment and theory

Absolute total electron-ion recombination rate coefficients of argonlike Sc3+(3s2 3p6) ions have been measured for relative energies between electrons and ions ranging from 0 to 45 eV. This energy range comprises all dielectronic recombination resonances attached to 3p -> 3d and 3p -> 4s excitations. A broad resonance with an experimental width of 0.89 +- 0.07 eV due to the 3p5 3d2 2F intermediate state is found at 12.31 +- 0.03 eV with a small experimental evidence for an asymmetric line shape. From R-Matrix and perturbative calculations we infer that the asymmetric line shape may not only be due to quantum mechanical interference between direct and resonant recombination channels as predicted by Gorczyca et al. [Phys. Rev. A 56, 4742 (1997)], but may partly also be due to the interaction with an adjacent overlapping DR resonance of the same symmetry. The overall agreement between theory and experiment is poor. Differences between our experimental and our theoretical resonance positions are as large as 1.4 eV. This illustrates the difficulty to accurately describe the structure of an atomic system with an open 3d-shell with state-of-the-art theoretical methods. Furthermore, we find that a relativistic theoretical treatment of the system under study is mandatory since the existence of experimentally observed strong 3p5 3d2 2D and 3p5 3d 4s 2D resonances can only be explained when calculations beyond LS-coupling are carried out.Comment: 11 pages, 7 figures, 3 tables, Phys. Rev. A (in print), see also: http://www.strz.uni-giessen.de/~k

The Role of Focal Adhesion Kinase Binding in the Regulation of Tyrosine Phosphorylation of Paxillin

Focal adhesion kinase (FAK) and paxillin are focal adhesion-associated, phosphotyrosine-containing proteins that physically interact. A previous study has demonstrated that paxillin contains two binding sites for FAK. We have further characterized these two binding sites and have demonstrated that the binding affinity of the carboxyl-terminal domain of FAK is the same for each of the two binding sites. The presence of both binding sites increases the affinity for FAK by 5-10-fold. A conserved paxillin sequence called the LD motif has been implicated in FAK binding. We show that mutations in the LD motifs in both FAK-binding sites are required to dramatically impair FAK binding in vitro. A paxillin mutant containing point mutations in both FAK-binding sites was characterized. The mutant exhibited reduced levels of phosphotyrosine relative to wild type paxillin in subconfluent cells growing in culture, following cell adhesion to fibronectin and in src-transformed fibroblasts. These results suggest that paxillin must bind FAK for maximal phosphorylation in response to cell adhesion and that FAK may function to direct tyrosine phosphorylation of paxillin in the process of transformation by the src oncogene

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles

SummaryMutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in AML patients without known FLT3 mutations and experimentally tested the consequences of each candidate leukemogenic allele. This approach identified gain-of-function mutations that activated downstream signaling and conferred sensitivity to FLT3 inhibition and alleles that were not associated with kinase activation, including mutations in the catalytic domain. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation and underscore the importance of functional studies to distinguish “driver” mutations underlying tumorigenesis from biologically neutral “passenger” alterations