Higher Resolution VLBI Imaging with Fast Frequency Switching

Millimetre-VLBI is an important tool in AGN astrophysics, but it is limited by short atmospheric coherence times and poor receiver and antenna performance. We demonstrate a new kind of phase referencing for the VLBA, enabling us to increase the sensitivity in mm-VLBI by an order of magnitude. If a source is observed in short cycles between the target frequency, nu_t, and a reference frequency, nu_ref, the nu_t data can be calibrated using scaled-up phase solutions from self-calibration at nu_ref. We have demonstrated the phase transfer on 3C 279, where we were able to make an 86 GHz image with 90 % coherence compared to self-calibration at nu_t. We have detected M81, our science target in this project, at 86 GHz using the same technique. We describe scheduling strategy and data reduction. The main impacts of fast frequency switching are the ability to image some of the nearest, but relatively weak AGN cores with unprecedented high angular resolution and to phase-reference the nu_t data to the nu_ref core position, enabling the detection of possible core shifts in jets due to optical depth effects. This ability will yield important constraints on jet properties and might be able to discriminate between the two competing emission models of Blandford-Konigl jets and spherical advection-dominated accretion flows (ADAFs) in low-luminosity AGNs.Comment: 4 pages, 6 figures, appears in: Proceedings of the 6th European VLBI Network Symposium held on June 25th-28th in Bonn, Germany. Edited by: E. Ros, R.W. Porcas, A.P. Lobanov, and J.A. Zensu

Rapid Real-Time Interdisciplinary Ocean Forecasting Using Adaptive Sampling and Adaptive Modeling and Legacy Codes: Component Encapsulation Using XML

Abstract. We present the high level architecture of a real-time inter-disciplinary ocean forecasting system that employs adaptive elements in both modeling and sampling. We also discuss an important issue that arises in creating an integrated, web-accessible framework for such a system out of existing stand-alone components: transparent support for handling legacy binaries. Such binaries, that are most common in scien-tific applications, expect a standard input stream, maybe some command line options, a set of input files and generate a set of output files as well as standard output and error streams. Legacy applications of this form are encapsulated using XML. We present a method that uses XML doc-uments to describe the parameters for executing a binary.

Evolution of motif variants and positional bias of the cyclic-AMP response element

BACKGROUND: Transcription factors regulate gene expression by interacting with their specific DNA binding sites. Some transcription factors, particularly those involved in transcription initiation, always bind close to transcription start sites (TSS). Others have no such preference and are functional on sites even tens of thousands of base pairs (bp) away from the TSS. The Cyclic-AMP response element (CRE) binding protein (CREB) binds preferentially to a palindromic sequence (TGACGTCA), known as the canonical CRE, and also to other CRE variants. CREB can activate transcription at CREs thousands of bp away from the TSS, but in mammals CREs are found far more frequently within 1 to 150 bp upstream of the TSS than in any other region. This property is termed positional bias. The strength of CREB binding to DNA is dependent on the sequence of the CRE motif. The central CpG dinucleotide in the canonical CRE (TGACGTCA) is critical for strong binding of CREB dimers. Methylation of the cytosine in the CpG can inhibit binding of CREB. Deamination of the methylated cytosines causes a C to T transition, resulting in a functional, but lower affinity CRE variant, TGATGTCA. RESULTS: We performed genome-wide surveys of CREs in a number of species (from worm to human) and showed that only vertebrates exhibited a CRE positional bias. We performed pair-wise comparisons of human CREs with orthologous sequences in mouse, rat and dog genomes and found that canonical and TGATGTCA variant CREs are highly conserved in mammals. However, when orthologous sequences differ, canonical CREs in human are most frequently TGATGTCA in the other species and vice-versa. We have identified 207 human CREs showing such differences. CONCLUSION: Our data suggest that the positional bias of CREs likely evolved after the separation of urochordata and vertebrata. Although many canonical CREs are conserved among mammals, there are a number of orthologous genes that have canonical CREs in one species but the TGATGTCA variant in another. These differences are likely due to deamination of the methylated cytosines in the CpG and may contribute to differential transcriptional regulation among orthologous genes

Transcriptional activation of the human brain-derived neurotrophic factor gene promoter III by dopamine signaling in NT2/N neurons

We have identified a functional cAMP-response element (CRE) in the human brain-derived neurotrophic factor (BDNF) gene promoter III and established that it participated in the modulation of BDNF expression in NT2/N neurons via downstream signaling from the D1 class of dopamine (DA) receptors. The up-regulation of BDNF expression, in turn, produced neuroprotective signals through receptor tyrosine kinase B (TrkB) and promoted cell survival under the conditions of oxygen and glucose deprivation. To our knowledge this is the first evidence showing the presence of a functional CRE in the human BDNF gene and the role of DA signaling in establishing transcriptional competence of CRE in post-mitotic NT2/N neurons. This ability of DA to regulate the expression of the BDNF survival factor has a profound significance for the nigrostriatal pathway, because it indicates the existence of a feedback loop between the neutrophin, which promotes both the maturation and survival of dopaminergic neurons, and the neurotransmitter, which the mature neurons ultimately produce and release

Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains

BACKGROUND: Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed genes that are expressed at high or moderate levels. Complementary to this approach, we described here a novel technology designed specifically to isolate rare and novel genes previously undetectable by other methods. We have used this method to identify differentially expressed genes in brains affected by AD. Our method, termed Subtractive Transcription-based Amplification of mRNA (STAR), is a combination of subtractive RNA/DNA hybridization and RNA amplification, which allows the removal of non-differentially expressed transcripts and the linear amplification of the differentially expressed genes. RESULTS: Using the STAR technology we have identified over 800 differentially expressed sequences in AD brains, both up- and down- regulated, compared to age-matched controls. Over 55% of the sequences represent genes of unknown function and roughly half of them were novel and rare discoveries in the human brain. The expression changes of nearly 80 unique genes were further confirmed by qRT-PCR and the association of additional genes with AD and/or neurodegeneration was established using an in-house literature mining tool (LitMiner). CONCLUSION: The STAR process significantly amplifies unique and rare sequences relative to abundant housekeeping genes and, as a consequence, identifies genes not previously linked to AD. This method also offers new opportunities to study the subtle changes in gene expression that potentially contribute to the development and/or progression of AD

Synchronization of Integrate and Fire oscillators with global coupling

In this article we study the behavior of globally coupled assemblies of a large number of Integrate and Fire oscillators with excitatory pulse-like interactions. On some simple models we show that the additive effects of pulses on the state of Integrate and Fire oscillators are sufficient for the synchronization of the relaxations of all the oscillators. This synchronization occurs in two forms depending on the system: either the oscillators evolve ``en bloc'' at the same phase and therefore relax together or the oscillators do not remain in phase but their relaxations occur always in stable avalanches. We prove that synchronization can occur independently of the convexity or concavity of the oscillators evolution function. Furthermore the presence of disorder, up to some level, is not only compatible with synchronization, but removes some possible degeneracy of identical systems and allows new mechanisms towards this state.Comment: 37 pages, 19 postscript figures, Latex 2

Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children

Background and Aim: The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. Hypothesis: We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. Methods:: 30 children (19 females, 10.7 ± 0.8 years of age; mean ± SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Analyses: Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Results and Conclusions: Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e., the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills