Epigenetic Profiling Reveals a Developmental Decrease in Promoter Accessibility During Cortical Maturation in vivo

Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve axon growth in other cell types, including combinatorial overexpression of AP1 factors, overexpression of histone acetyltransferases, and pharmacological inhibitors of histone deacetylases. This insensitivity could be due to intermediate chromatin closure at the time of culture, and highlights important differences in cell culture models used to test potential pro-regenerative interventions

SIRS dynamics on random networks: simulations and analytical models

The standard pair approximation equations (PA) for the Susceptible-Infective-Recovered-Susceptible (SIRS) model of infection spread on a network of homogeneous degree $k$ predict a thin phase of sustained oscillations for parameter values that correspond to diseases that confer long lasting immunity. Here we present a study of the dependence of this oscillatory phase on the parameter $k$ and of its relevance to understand the behaviour of simulations on networks. For $k=4$, we compare the phase diagram of the PA model with the results of simulations on regular random graphs (RRG) of the same degree. We show that for parameter values in the oscillatory phase, and even for large system sizes, the simulations either die out or exhibit damped oscillations, depending on the initial conditions. This failure of the standard PA model to capture the qualitative behaviour of the simulations on large RRGs is currently being investigated.Comment: 6 pages, 3 figures, WIPP to be published in Conference proceedings Complex'2009 February 23-25, Shanghai, Chin

Machine Assisted Proof of ARMv7 Instruction Level Isolation Properties

In this paper, we formally verify security properties of the ARMv7 Instruction Set Architecture (ISA) for user mode executions. To obtain guarantees that arbitrary (and unknown) user processes are able to run isolated from privileged software and other user processes, instruction level noninterference and integrity properties are provided, along with proofs that transitions to privileged modes can only occur in a controlled manner. This work establishes a main requirement for operating system and hypervisor verification, as demonstrated for the PROSPER separation kernel. The proof is performed in the HOL4 theorem prover, taking the Cambridge model of ARM as basis. To this end, a proof tool has been developed, which assists the verification of relational state predicates semi-automatically

The Application of CRISPR Technology to High Content Screening in Primary Neurons

Axon growth is coordinated by multiple interacting proteins that remain incompletely characterized. High content screening (HCS), in which manipulation of candidate genes is combined with rapid image analysis of phenotypic effects, has emerged as a powerful technique to identify key regulators of axon outgrowth. Here we explore the utility of a genome editingapproach referred to as CRISPR (Clustered Regularly Interspersed Palindromic Repeats) for knockout screening in primary neurons. In the CRISPR approach a DNA-cleaving Cas enzyme is guided to genomic target sequences by user-created guide RNA (sgRNA), where it initiates a double-stranded break that ultimately results in frameshift mutation and loss of protein production. Using electroporation of plasmid DNA that co-expresses Cas9enzyme and sgRNA, we first verified the ability of CRISPR targeting to achieve protein-level knockdown in cultured postnatal cortical neurons. Targeted proteins included NeuN (RbFox3) and PTEN, a well-studied regulator of axon growth. Effective knockdown lagged at least four days behind transfection, but targeted proteins were eventually undetectable by immunohistochemistry in \u3e 80% of transfected cells. Consistent with this, anti-PTEN sgRNA produced no changes in neurite outgrowth when assessed three days post-transfection. When week-long cultures were replated, however, PTEN knockdown consistently increased neurite lengths. These CRISPR-mediated PTEN effects were achieved using multi-well transfection and automated phenotypic analysis, indicating the suitability of PTEN as a positive control for future CRISPR-based screening efforts. Combined, these data establish an example of CRISPR-mediated protein knockdown in primary cortical neurons and its compatibility with HCS workflows

Digging supplementary buried channels: investigating the notch architecture within the CCD pixels on ESA's Gaia satellite

The European Space Agency (ESA) Gaia satellite has 106 CCD image sensors which will suffer from increased charge transfer inefficiency (CTI) as a result of radiation damage. To aid the mitigation at low signal levels, the CCD design includes Supplementary Buried Channels (SBCs, otherwise known as `notches') within each CCD column. We present the largest published sample of Gaia CCD SBC Full Well Capacity (FWC) laboratory measurements and simulations based on 13 devices. We find that Gaia CCDs manufactured post-2004 have SBCs with FWCs in the upper half of each CCD that are systematically smaller by two orders of magnitude (<50 electrons) compared to those manufactured pre-2004 (thousands of electrons). Gaia's faint star (13 < G < 20 mag) astrometric performance predictions by Prod'homme et al. and Holl et al. use pre-2004 SBC FWCs as inputs to their simulations. However, all the CCDs already integrated onto the satellite for the 2013 launch are post-2004. SBC FWC measurements are not available for one of our five post-2004 CCDs but the fact it meets Gaia's image location requirements suggests it has SBC FWCs similar to pre-2004. It is too late to measure the SBC FWCs onboard the satellite and it is not possible to theoretically predict them. Gaia's faint star astrometric performance predictions depend on knowledge of the onboard SBC FWCs but as these are currently unavailable, it is not known how representative of the whole focal plane the current predictions are. Therefore, we suggest Gaia's initial in-orbit calibrations should include measurement of the onboard SBC FWCs. We present a potential method to do this. Faint star astrometric performance predictions based on onboard SBC FWCs at the start of the mission would allow satellite operating conditions or CTI software mitigation to be further optimised to improve the scientific return of Gaia.Comment: Accepted for publication in MNRAS, 16 pages, 19 figure

Ultra-fine beryllium powder by amalgam process Progress report, period ending 31 Oct. 1966

Metallurgical evaluation of beryllium powdered metal, and electron microscope studies of agglomerate particle size

The bar PANDA focussing-lightguide disc DIRC

bar PANDA will be a fixed target experiment internal to the HESR antiproton storage ring at the future FAIR complex. The ANDA detector requires excellent particle-identification capabilities in order to achieve its scientific potential. Cherenkov counters employing the DIRC principle were chosen as PID detectors for the Target Spectrometer. The proposed Focussing-Lightguide Disc DIRC will cover the forward part of the Target Spectrometer acceptance in the angular range between 5° and 22°. Its design includes a novel approach to mitigate dispersion effects in the solid radiator of a DIRC counter using optical elements. The dispersion correction will enable the Focussing-Lightguide Disc DIRC to provide pion-kaon identification for momenta well above 3.5 GeV/c

Ion-Molecule Reactions in Unsaturated Hydrocarbons: Allene, Propyne, Diacetylene, and Vinylacetylene

Ion-molecule reactions in allene, propyne, diacetylene, and vinylacetylene (1-buten-3-yne) have been studied at near-thermal energies by the technique of ion cyclotron resonance mass spectrometry. Rate coefficients and branching ratios are reported for the reactions of C_3H^+_n (n = 1-4) with allene and propyne and for the reactions of C_4H^+_n (n = 0-5) with diacetylene and vinylacetylene. Branching ratios are also given for the reactions of C_4H^+_n, C_5H_n, and C_6H^+_n with propyne and for reactions of C_6H^+_n with diacetylene and vinylacetylene. More than 90% of the reactive channels lead to product ions having a larger carbon skeleton than the reactant ion. Evidence for ions with the same m/e ratio having differing reactivities was obtained for C_3H^+_3, C_6H^+_7, and C_7H^+_7. Ion reaction sequences in allene and propyne were followed at higher pressures (l0^(-4) torr) to investigate secondary, tertiary, and higher order processes