The relation between time of presentation and the sleep disturbing effects of nocturnally occurring jet aircraft flyovers

The research describes the sleep disturbing effects of jet aircraft flyover noise as it occurs at different times during the night. The results indicate that individuals respond statistically more, in terms of greater cortical desynchronization, during the first and last thirds of the night. During the middle third, while there is still a significant amount of cortical desynchronization in response to the jet aircraft noise, this is always less than that which occurs earlier or later in the night. The implications of this data are that it might be possible to reduce the disruptive effects of at least certain extrinsic sonic stimulation by appropriate scheduling

Sampling, Intervention, Prediction, Aggregation: A Generalized Framework for Model-Agnostic Interpretations

Model-agnostic interpretation techniques allow us to explain the behavior of any predictive model. Due to different notations and terminology, it is difficult to see how they are related. A unified view on these methods has been missing. We present the generalized SIPA (sampling, intervention, prediction, aggregation) framework of work stages for model-agnostic interpretations and demonstrate how several prominent methods for feature effects can be embedded into the proposed framework. Furthermore, we extend the framework to feature importance computations by pointing out how variance-based and performance-based importance measures are based on the same work stages. The SIPA framework reduces the diverse set of model-agnostic techniques to a single methodology and establishes a common terminology to discuss them in future work

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits

Binary-induced magnetic activity? Time-series echelle spectroscopy and photometry of HD123351 = CZ CVn

We present a first and detailed study of the bright and active K0IV-III star HD 123351. The star is found to be a single-lined spectroscopic binary with a period of 147.8919+-0.0003 days and a large eccentricity of e=0.8086+-0.0001. The rms of the orbital solution is just 47 m/s, making it the most precise orbit ever obtained for an active binary system. The rotation period is constrained from long-term photometry to be 58.32+-0.01 days. It shows that HD 123351 is a very asynchronous rotator, rotating five times slower than the expected pseudo-synchronous value. Two spotted regions persisted throughout the 12 years of our observations. Four years of Halpha, CaII H&K and HeI D3 monitoring identifies the same main periodicity as the photometry but dynamic spectra also indicate that there is an intermittent dependence on the orbital period, in particular for Ca ii H&K in 2008. Line-profile inversions of a pair of Zeeman sensitive/insensitive iron lines yield an average surface magnetic-flux density of 542+-72 G. The time series for 2008 is modulated by the stellar rotation as well as the orbital motion, such that the magnetic flux is generally weaker during times of periastron and that the chromospheric emissions vary in anti-phase with the magnetic flux. We also identify a broad and asymmetric lithium line profile and measure an abundance of log n(Li) = 1.70+-0.05. The star's position in the H-R diagram indicates a mass of 1.2+-0.1 Msun and an age of 6-7 Gyr. We interpret the anti-phase relation of the magnetic flux with the chromospheric emissions as evidence that there are two magnetic fields present at the same time, a localized surface magnetic field associated with spots and a global field that is oriented towards the (low-mass) secondary component

Antisolar differential rotation of the K1-giant sigma Geminorum revisited

Context. Surface differential rotation and other global surface flows on magnetically active stars are among the observable manifes- tations of the stellar dynamo working underneath. Therefore, such observations are important for stellar dynamo theory and useful constraints for solar dynamo studies as well. Aims. The active K1-giant component of the long-period RS CVn-type binary system σ Gem and its global surface flow pattern is revisited. Methods. We refine the differential rotation law from recovering the spot migration pattern. We apply a detailed cross-correlation technique to a unique set of 34 time-series Doppler images recovered using data from 1996/97. By increasing the number of the avail- able cross-correlation function maps from the formerly used 4 to 17 we expect a more robust determination of the differential surface rotation law. In addition, we present a new time-series Doppler imaging study of σ Gem using our advanced surface reconstruction code iMap for a dataset collected in 2006/07. Results. Results from the reprocessed cross-correlation study confirm that the star performs antisolar-type differential rotation with a surface shear α of −0.04 ± 0.01, i.e., almost a factor of two stronger compared to the previously claimed value. We also confirm the evidence of a global poleward spot migration with an average velocity of 0.21 ± 0.03 km s−1, in accordance with theoretical predictions. From the new observations we obtain three subsequent Doppler images. The time evolution of these images confirms the antisolar-type differential rotation of the same amount

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline