GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson\u27s Disease.

While GM1 may interact with α-synuclein in vitro to inhibit aggregation, the ability of GM1 to protect against α-synuclein toxicity in vivo has not been investigated. We used targeted adeno-associated viral vector (AAV) overexpression of human mutant α-synuclein (A53T) in the rat substantia nigra (SN) to produce degeneration of SN dopamine neurons, loss of striatal dopamine levels, and behavioral impairment. Some animals received daily GM1 ganglioside administration for 6 weeks, beginning 24 hours after AAV-A53T administration or delayed start GM1 administration for 5 weeks beginning 3 weeks after AAV-A53T administration. Both types of GM1 administration protected against loss of SN dopamine neurons and striatal dopamine levels, reduced α-synuclein aggregation, and delayed start administration of GM1 reversed early appearing behavioral deficits. These results extend prior positive results in MPTP models, are consistent with the results of a small clinical study of GM1 in PD patients that showed slowing of symptom progression with chronic use, and argue for the continued refinement and development of GM1 as a potential disease modifying therapy for PD

Turbulence transition and the edge of chaos in pipe flow

The linear stability of pipe flow implies that only perturbations of sufficient strength will trigger the transition to turbulence. In order to determine this threshold in perturbation amplitude we study the \emph{edge of chaos} which separates perturbations that decay towards the laminar profile and perturbations that trigger turbulence. Using the lifetime as an indicator and methods developed in (Skufca et al, Phys. Rev. Lett. {\bf 96}, 174101 (2006)) we show that superimposed on an overall $1/\Re$-scaling predicted and studied previously there are small, non-monotonic variations reflecting folds in the edge of chaos. By tracing the motion in the edge we find that it is formed by the stable manifold of a unique flow field that is dominated by a pair of downstream vortices, asymmetrically placed towards the wall. The flow field that generates the edge of chaos shows intrinsic chaotic dynamics.Comment: 4 pages, 5 figure

Visual motherese? Signal-to-noise ratios in toddler-directed television

Younger brains are noisier information processing systems; this means that information for younger individuals has to allow clearer differentiation between those aspects that are required for the processing task in hand (the ‘signal’) and those that are not (the ‘noise’). We compared toddler-directed and adult-directed TV programmes (TotTV/ATV). We examined how low-level visual features (that previous research has suggested influence gaze allocation) relate to semantic information, namely the location of the character speaking in each frame. We show that this relationship differs between TotTV and ATV. First, we conducted Receiver Operator Characteristics analyses and found that feature congestion predicted speaking character location in TotTV but not ATV. Second, we used multiple analytical strategies to show that luminance differentials (flicker) predict face location more strongly in TotTV than ATV. Our results suggest that TotTV designers have intuited techniques for controlling toddler attention using low-level visual cues. The implications of these findings for structuring childhood learning experiences away from a screen are discussed

Susceptibility Provision Enhances Effective De-escalation (SPEED): utilizing rapid phenotypic susceptibility testing in Gram-negative bloodstream infections and its potential clinical impact

Abstract Objectives We evaluated the performance and time to result for pathogen identification (ID) and antimicrobial susceptibility testing (AST) of the Accelerate Pheno™ system (AXDX) compared with standard of care (SOC) methods. We also assessed the hypothetical improvement in antibiotic utilization if AXDX had been implemented. Methods Clinical samples from patients with monomicrobial Gram-negative bacteraemia were tested and compared between AXDX and the SOC methods of the VERIGENE® and Bruker MALDI Biotyper® systems for ID and the VITEK® 2 system for AST. Additionally, charts were reviewed to calculate theoretical times to antibiotic de-escalation, escalation and active and optimal therapy Results ID mean time was 21 h for MALDI-TOF MS, 4.4 h for VERIGENE® and 3.7 h for AXDX. AST mean time was 35 h for VITEK® 2 and 9.0 h for AXDX. For ID, positive percentage agreement was 95.9% and negative percentage agreement was 99.9%. For AST, essential agreement was 94.5% and categorical agreement was 93.5%. If AXDX results had been available to inform patient care, 25% of patients could have been put on active therapy sooner, while 78% of patients who had therapy optimized during hospitalization could have had therapy optimized sooner. Additionally, AXDX could have reduced time to de-escalation (16 versus 31 h) and escalation (19 versus 31 h) compared with SOC. Conclusions By providing fast and reliable ID and AST results, AXDX has the potential to improve antimicrobial utilization and enhance antimicrobial stewardship

Magnetic White Dwarfs from the SDSS II. The Second and Third Data Releases

Fifty-two magnetic white dwarfs have been identified in spectroscopic observations from the Sloan Digital Sky Survey (SDSS) obtained between mid-2002 and the end of 2004, including Data Releases 2 and 3. Though not as numerous nor as diverse as the discoveries from the first Data Release, the collection exhibits polar field strengths ranging from 1.5MG to ~1000MG, and includes two new unusual atomic DQA examples, a molecular DQ, and five stars that show hydrogen in fields above 500MG. The highest-field example, SDSSJ2346+3853, may be the most strongly magnetic white dwarf yet discovered. Analysis of the photometric data indicates that the magnetic sample spans the same temperature range as for nonmagnetic white dwarfs from the SDSS, and support is found for previous claims that magnetic white dwarfs tend to have larger masses than their nonmagnetic counterparts. A glaring exception to this trend is the apparently low-gravity object SDSSJ0933+1022, which may have a history involving a close binary companion.Comment: 20 pages, 4 figures Accepted for publication in the Astronomical Journa

An Empirical Calibration of the Completeness of the SDSS Quasar Survey

Spectra of nearly 20000 point-like objects to a Galactic reddening corrected magnitude of i=19.1 have been obtained to test the completeness of the SDSS quasar survey. The spatially-unresolved objects were selected from all regions of color space, sparsely sampled from within a 278 sq. deg. area of sky covered by this study. Only ten quasars were identified that were not targeted as candidates by the SDSS quasar survey (including both color and radio source selection). The inferred density of unresolved quasars on the sky that are missed by the SDSS algorithm is 0.44 per sq. deg, compared to 8.28 per sq. deg. for the selected quasar density, giving a completeness of 94.9(+2.6,-3.8) to the limiting magnitude. Omitting radio selection reduces the color-only selection completeness by about 1%. Of the ten newly identified quasars, three have detected broad absorption line systems, six are significantly redder than other quasars at the same redshift, and four have redshifts between 2.7 and 3.0 (the redshift range where the SDSS colors of quasars intersect the stellar locus). The fraction of quasars missed due to image defects and blends is approximately 4%, but this number varies by a few percent with magnitude. Quasars with extended images comprise about 6% of the SDSS sample, and the completeness of the selection algorithm for extended quasars is approximately 81%, based on the SDSS galaxy survey. The combined end-to-end completeness for the SDSS quasar survey is approximately 89%. The total corrected density of quasars on the sky to i=19.1 is estimated to be 10.2 per sq. deg.Comment: 37 pages, 10 figures, accepted for publication in A

Additional Ultracool White Dwarfs Found in the Sloan Digital Sky Survey

We identify seven new ultracool white dwarfs discovered in the Sloan Digital Sky Survey (SDSS). The SDSS photometry, spectra, and proper motions are presented, and additional BVRI data are given for these and other previously discovered ultracool white dwarfs. The observed colors span a remarkably wide range, qualitatively similar to colors predicted by models for very cool white dwarfs. One of the new stars (SDSS J1251+44) exhibits strong collision-induced absorption (CIA) in its spectra, while the spectra and colors of the other six are consistent with mild CIA. Another of the new discoveries (SDSS J2239+00A) is part of a binary system -- its companion is also a cool white dwarf, and other data indicate that the companion exhibits an infrared flux deficiency, making this the first binary system composed of two CIA white dwarfs. A third discovery (SDSS J0310-00) has weak Balmer emission lines. The proper motions of all seven stars are consistent with membership in the disk or thick disk.Comment: Accepted for Astrophysical Journal. 16 pages (includes 3 figures

Four problems with global carbon markets: a critical review

This article offers a critique of global carbon markets and trading, with a special focus on the Clean Development Mechanism of the Kyoto Protocol. It explores problems with the use of tradable permits to address climate change revolving around four areas: homogeneity, justice, gaming, and information. Homogeneity problems arise from the non-linear nature of climate change and sensitivity of emissions, which complicate attempts to calculate carbon offsets. Justice problems involve issues of dependency and the concentration of wealth among the rich, meaning carbon trading often counteracts attempts to reduce poverty. Gaming problems include pressures to promote high-volume, least-cost projects and the consequences of emissions leakage. Information problems encompass transaction costs related to carbon trading and market participation and the comparatively weak institutional capacity of project evaluators

New Constraints on Cosmic Reionization from the 2012 Hubble Ultra Deep Field Campaign

Understanding cosmic reionization requires the identification and characterization of early sources of hydrogen-ionizing photons. The 2012 Hubble Ultra Deep Field (UDF12) campaign has acquired the deepest infrared images with the Wide Field Camera 3 aboard Hubble Space Telescope and, for the first time, systematically explored the galaxy population deep into the era when cosmic microwave background (CMB) data indicates reionization was underway. The UDF12 campaign thus provides the best constraints to date on the abundance, luminosity distribution, and spectral properties of early star-forming galaxies. We synthesize the new UDF12 results with the most recent constraints from CMB observations to infer redshift-dependent ultraviolet (UV) luminosity densities, reionization histories, and electron scattering optical depth evolution consistent with the available data. Under reasonable assumptions about the escape fraction of hydrogen ionizing photons and the intergalactic medium clumping factor, we find that to fully reionize the universe by redshift z~6 the population of star-forming galaxies at redshifts z~7-9 likely must extend in luminosity below the UDF12 limits to absolute UV magnitudes of M_UV\sim -13 or fainter. Moreover, low levels of star formation extending to redshifts z~15-25, as suggested by the normal UV colors of z\simeq7-8 galaxies and the smooth decline in abundance with redshift observed by UDF12 to z\simeq10, are additionally likely required to reproduce the optical depth to electron scattering inferred from CMB observations.Comment: Version accepted by ApJ (originally submitted Jan 5, 2013). The UDF12 website can be found at http://udf12.arizona.ed