M2I-1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti-mitotic drugs via MCL-1s

Background Drugs such as taxanes, epothilones, and vinca alkaloids are widely used in the treatment of breast, ovarian, and lung cancers but come with major side effects such as neuropathy and loss of neutrophils and as single agents have a lack of efficacy. M2I-1 (MAD2 inhibitor-1) has been shown to disrupt the CDC20-MAD2 interaction, and consequently, the assembly of the mitotic checkpoint complex (MCC). Results We report here that M2I-1 can significantly increase the sensitivity of several cancer cell lines to anti-mitotic drugs, with cell death occurring after a prolonged mitotic arrest. In the presence of nocodazole or taxol combined with M2I-1 cell death is triggered by the premature degradation of Cyclin B1, the perturbation of the microtubule network, and an increase in the level of the pro-apoptotic protein MCL-1s combined with a marginal increase in the level of NOXA. The elevated level of MCL-1s and the marginally increased NOXA antagonized the increased level of MCL-1, a pro-survival protein of the Bcl-2 family. Conclusion Our results provide some important molecular mechanisms for understanding the relationship between the mitotic checkpoint and programmed cell death and demonstrate that M2I-1 exhibits antitumor activity in the presence of current anti-mitotic drugs such as taxol and nocodazole and has the potential to be developed as an anticancer agent

A nearly symmetric double-image gravitational lens

We report the discovery of a new double-image gravitational lens resulting from our search for lenses in the southern sky. Radio source PMN J2004-1349 is composed of two compact components separated by 1.13 arcseconds in VLA, MERLIN and VLBA images. The components have a flux ratio of 1:1 at radio frequencies ranging from 5 GHz to 22 GHz. The I-band optical counterpart is also an equal double, with roughly the same separation and position angle as the radio double. Upon subtraction of the components from the I-band image, we identify a dim pattern of residuals as the lens galaxy. While the present observations are sufficient to establish that J2004-1349 is a gravitational lens, additional information will be necessary (such as the redshifts of the galaxy and quasar, and precise astrometry and photometry of the lens galaxy) before constructing detailed mass models.Comment: 17 pp., 5 bitmapped figs. (contact [email protected] for nicer figs), in press, A.J. (substantially revised

A Keck/HIRES Doppler Search for Planets Orbiting Metal-Poor Dwarfs. I. Testing Giant Planet Formation and Migration Scenarios

We describe a high-precision Doppler search for giant planets orbiting a well-defined sample of metal-poor dwarfs in the field. This experiment constitutes a fundamental test of theoretical predictions which will help discriminate between proposed giant planet formation and migration models. We present here details on the survey as well as an overall assessment of the quality of our measurements, making use of the results for the stars that show no significant velocity variation.Comment: 25 pages, 7 figures, accepted for publication in the Astrophysical Journa

Impact of Clopidogrel Pretreatment on Ischemic Complications of PCI among Bivalirudin-Treated Patients: Results from the EVENT Registry

Computational Infrastructure and Informatics Poster SessionBackground: Although clopidogrel (CLO) pretreatment benefits PCI patients with acute coronary syndromes, these benefits are less well-established among elective PCI patients—particularly when treated with the direct thrombin inhibitor (DTI), bivalirudin. The effect of timing of CLO pretreatment on ischemic complications in these patients is also unknown. Methods: We used data from the multicenter EVENT registry to assess the association of clopidogrel pretreatment (600 mg 2 hr pre-PCI, 300 mg 6 hrs pre-PCI, or 75 mg/d for 1 week) with PCI-related complications in patients undergoing elective PCI with a DTI as planned antithrombotic. The primary endpoint was the composite of in-hospital death or MI (peak CKMB > 3 x ULN). Results: Between 01/05 and 12/07, 3568 pts underwent elective PCI and 1913 (54%) received DTI as planned anticoagulant (37% diabetics, age 65±10 y). Clopidogrel pre-treatment was used in 923 (48%). There were no differences in in-hospital or 1 year ischemic or bleeding events in relation to clopidogrel pretreatment in both unadjusted and adjusted analyses (see Table). There was a trend toward lower rates of death or MI with earlier pretreatment, however [Odds ratios vs. no pretreatment: >1 week 0.48 (95% CI 0.08 - 2.73); > 6 h OR 0.69 (95% CI 0.11 - 4.45) and 2-6 h OR 0.77 (95% CI 0.18 - 3.31)]. Conclusion: Among unselected patients undergoing elective PCI with DTI as the planned anticoagulant, clopidogrel pretreatment was common, but was not associated with a reduced risk of ischemic complications

Galaxy and mass assembly (GAMA): End of survey report and data release 2

The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of lowredshift galaxies. Covering an area of ~286 deg2 (split among five survey regions) down to a limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238 000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm-1 m. Here, we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release ofGAMAdata. In this release, we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component Śersic fits, stellar masses, Hα-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72 225 objects in total). The data base serving these data is available at http://www.gama-survey.org/

Effects of a dietary supplement on golf drive distance and functional indices of golf performance

Background Limited research exists examining the impact of nutrition on golfing performance. This study’s purpose was to determine the impact of daily supplementation with an over-the-counter dietary supplement on golf performance. Methods Healthy men (30.3 ± 6.9 y, 183.1 ± 5.6 cm, 86.7 ± 11.9 kg), with a 5–15 handicap were assigned in a double-blind, placebo-controlled manner to ingest for 30 days either a placebo (PLA, n = 13) or a dietary supplement containing creatine monohydrate, coffea arabica fruit extract, calcium fructoborate and vitamin D (Strong Drive™, SD, n = 14). Subjects ingested two daily doses for the first two weeks and one daily dose for the remaining two weeks. Participants followed their normal dietary habits and did not change their physical activity patterns. Two identical testing sessions in a pre/post fashion were completed consisting of a fasting blood sample, anthropometric measurements, 1-RM bench press, upper body power and golf swing performance using their driver and 7-iron. Data were analyzed using two-way mixed factorial ANOVAs and ANCOVA when baseline differences were present. Statistical significance was established a priori at p ≤ 0.05. Results ANCOVA revealed significantly greater (post-test) best drive distance (p = 0.04) for SD (+5.0% [+13.6 yards], ES = 0.75) as well as a tendency (p = 0.07) for average drive distance to increase (+8.4% [+19.6 yards], ES = 0.65), while no such changes were found with PLA (−0.5% [−1.2 yards], ES = 0.04 and +1.3% [+2.8 yards], ES = 0.08, respectively). Both groups experienced significant increases in body mass and 1-RM bench press (p \u3c 0.001). No other significant group × time interactions were found. For the SD group only, within-group analysis confirmed significant improvements in set 1 average (+8.9%, p = 0.001) and peak velocity (+6.8%, p \u3c =0.01). No changes were noted for reported adverse events, pain inventories, quality of life or any measured blood parameter. Conclusions SD supplementation for 30 days significantly improved best drive distance more than placebo. Supplementation was well tolerated and did not result in any clinically significant changes in markers of health or adverse events/side effect profiles

Formation of Ferroelectrically Defined Ag Nanoarray Patterns

In order to produce the most effective Ag nanoarrays for plasmon enhanced fluorescence and Raman scattering made using ferroelectric substrates, the optimum conditions for the creation of arrays must be identified. We study here Ag nanopattern arrays formed using ferroelectric lithography based on periodically proton exchanged (PPE) template methods. We examine different conditions in regard to deposition of Ag nanoparticles and analyze the plasmon enhanced signal from the resulting nanoarray. We apply FLIM (fluorescence lifetime imaging) to assess different Ag nanoarray preparation conditions on fluorescence emission from selected fluorphores. In addition, we apply Raman and luminescence spectroscopy with AFM (atomic force microscopy) to study the plasmon enhancement of luminescence and Raman from the Ag nanoarrays

Probing Unstable Massive Neutrinos with Current Cosmic Microwave Background Observations

The pattern of anisotropies in the Cosmic Microwave Background depends upon the masses and lifetimes of the three neutrino species. A neutrino species of mass greater than 10 eV with lifetime between 10^{13} sec and 10^{17} sec leaves a very distinct signature (due to the integrated Sachs-Wolfe effect): the anisotropies at large angles are predicted to be comparable to those on degree scales. Present data exclude such a possibility and hence this region of parameter space. For $m_\nu \simeq 30$ eV, $\tau \simeq 10^{13}$ sec, we find an interesting possibility: the Integrated Sachs Wolfe peak produced by the decaying neutrino in low-$\Omega$ models mimics the acoustic peak expected in an $\Omega = 1$ model.Comment: 5 pages, 4 figure