Towards scalable parallel-in-time turbulent flow simulations

We present a reformulation of unsteady turbulent flow simulations. The initial condition is relaxed and information is allowed to propagate both forward and backward in time. Simulations of chaotic dynamical systems with this reformulation can be proven to be well-conditioned time domain boundary value problems. The reformulation can enable scalable parallel-in-time simulation of turbulent flows.United States. Air Force Office of Scientific Research. Small Business Technology Transfer Program (Contract FA9550-12-C-0065

Predicting Driver Safety in Parkinson’s Disease: An Interim Report of an Ongoing Longitudinal Study

This article summarizes the baseline results of an ongoing longitudinal, NIH-funded study on prediction of driver safety in patients with Parkinson’s disease (PD). Patients with even mild to moderate PD who drive and live independently suffer from visual and cognitive dysfunction, which appear to be the main contributors to decreased driving performance and safety, rather than the motor dysfunction for which PD is known

Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n−6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n−6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n−6 AA and increased D6D activity can lead to enhanced n−6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention

Cognitive Abilities Related to Driving Performance in a Simulator and Crashing on the Road

The purpose of this study was to examine the relationships between performances on standardized neuropsychological measures of cognitive abilities, simulated driving performance, and state crash records in drivers with cognitive decline due to aging and dementia. Participants were 202 experienced older adult drivers ages 55 years and older: 70 had mild dementia due to probable early Alzheimer’s disease and 132 had no neurologic disease. All completed a battery of neuropsychological tests and drove contemporaneously on a high fidelity simulator. The participants’ State Department of Transportation driving records were monitored for up to two years after testing. The simulator composite score, reflecting overall driving ability, was significantly correlated with overall cognitive ability, as indexed by the neuropsychology composite score, as well as with individual cognitive tests of attention, memory, visuospatial and visuomotor abilities. Drivers who crashed during an intersection incursion scenario performed significantly worse on the composite measure of cognitive function than those who successfully steered around the incurring vehicle. Crashers had specific cognitive deficits on measures of visuomotor abilities and attention. Memory test performances for both verbal information and visual material were associated with subsequent on-road crashes. These findings provide support for the validity of driving simulation as a safe means of evaluating a range of driving responses that cannot be tested on the road, and suggest that relatively simple and inexpensive neuropsychological tests of specific cognitive abilities could be used to help evaluate older drivers’ risk of unsafe drivin

Possible detection of two giant extrasolar planets orbiting the eclipsing polar UZ Fornacis

We present new high-speed, multi-observatory, multi-instrument photometry of the eclipsing polar UZ For in order to measure precise mid-eclipse times with the aim of detecting any orbital period variations. When combined with published eclipse times and archival data spanning ~27 years, we detect departures from a linear and quadratic trend of ~60 s. The departures are strongly suggestive of two cyclic variations of 16(3) and 5.25(25) years. The two favoured mechanisms to drive the periodicities are either two giant extrasolar planets as companions to the binary (with minimum masses of 6.3(1.5)M(Jupiter) and 7.7(1.2)M(Jupiter)) or a magnetic cycle mechanism (e.g. Applegate's mechanism) of the secondary star. Applegate's mechanism would require the entire radiant energy output of the secondary and would therefore seem to be the least likely of the two, barring any further refinements in the effect of magnetic fieilds (e.g. those of Lanza et al.). The two planet model can provide realistic solutions but it does not quite capture all of the eclipse times measurements. A highly eccentric orbit for the outer planet would fit the data nicely, but we find that such a solution would be unstable. It is also possible that the periodicities are driven by some combination of both mechanisms. Further observations of this system are encouraged.Comment: 10 pages, 4 figures, 2 table

Experimentally Engineering the Edge Termination of Graphene Nanoribbons

The edges of graphene nanoribbons (GNRs) have attracted much interest due to their potentially strong influence on GNR electronic and magnetic properties. Here we report the ability to engineer the microscopic edge termination of high quality GNRs via hydrogen plasma etching. Using a combination of high-resolution scanning tunneling microscopy and first-principles calculations, we have determined the exact atomic structure of plasma-etched GNR edges and established the chemical nature of terminating functional groups for zigzag, armchair and chiral edge orientations. We find that the edges of hydrogen-plasma-etched GNRs are generally flat, free of structural reconstructions and are terminated by hydrogen atoms with no rehybridization of the outermost carbon edge atoms. Both zigzag and chiral edges show the presence of edge states.Comment: 16+9 pages, 3+4 figure

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Pharmacological Analysis of the Activation and Receptor Properties of the Tonic GABACR Current in Retinal Bipolar Cell Terminals

GABAergic inhibition in the central nervous system (CNS) can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABAA receptors (GABAARs) respectively. Retinal bipolar cells (BCs) exhibit a tonic current mediated by GABACRs in their axon terminal, in addition to synaptic GABAAR and GABACR currents, which strongly regulate BC output. The tonic GABACR current in BC terminals (BCTs) is not dependent on vesicular GABA release, but properties such as the alternative source of GABA and the identity of the GABACRs remain unknown. Following a recent report that tonic GABA release from cerebellar glial cells is mediated by Bestrophin 1 anion channels, we have investigated their role in non-vesicular GABA release in the retina. Using patch-clamp recordings from BCTs in goldfish retinal slices, we find that the tonic GABACR current is not reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by DIDS, which decreases the tonic current without directly affecting GABACRs. All three drugs also exhibit non-specific effects including inhibition of GABA transporters. GABACR ρ subunits can form homomeric and heteromeric receptors that differ in their properties, but BC GABACRs are thought to be ρ1-ρ2 heteromers. To investigate whether GABACRs mediating tonic and synaptic currents may differ in their subunit composition, as is the case for GABAARs, we have examined the effects of two antagonists that show partial ρ subunit selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABACR currents were differentially affected by both drugs, suggesting that a population of homomeric ρ1 receptors contributes to the tonic current. These results extend our understanding of the multiple forms of GABAergic inhibition that exist in the CNS and contribute to visual signal processing in the retina

Integrating water exclusion theory into βcontacts to predict binding free energy changes and binding hot spots

10.1186/1471-2105-15-57BMC Bioinformatics151-BBMI