Alternative mapping of probes to genes for Affymetrix chips

<p>Abstract</p> <p>Background</p> <p>Short oligonucleotide arrays have several probes measuring the expression level of each target transcript. Therefore the selection of probes is a key component for the quality of measurements. However, once probes have been selected and synthesized on an array, it is still possible to re-evaluate the results using an updated mapping of probes to genes, taking into account the latest biological knowledge available.</p> <p>Methods</p> <p>We investigated how probes found on recent commercial microarrays for human genes (Affymetrix HG-U133A) were matching a recent curated collection of human transcripts: the NCBI RefSeq database. We also built mappings and used them in place of the original probe to genes associations provided by the manufacturer of the arrays.</p> <p>Results</p> <p>In a large number of cases, 36%, the probes matching a reference sequence were consistent with the grouping of probes by the manufacturer of the chips. For the remaining cases there were discrepancies and we show how that can affect the analysis of data.</p> <p>Conclusions</p> <p>While the probes on Affymetrix arrays remain the same for several years, the biological knowledge concerning the genomic sequences evolves rapidly. Using up-to-date knowledge can apparently change the outcome of an analysis.</p

Complexity challenges for transition policy: lessons from coastal shipping in Norway

This policy briefing discusses decarbonization policies of “hard-to-abate” sectors, emphasizing the implications of these sectors’ complexity. Specifically, we discuss two sources of complexity: (a) heterogeneity in the form of variation across and within technologies and user segments and (b) interdependencies between technologies (within and between their value chains) and between user segments and adopter groups. Based on research on coastal shipping in Norway, a global frontrunner in decarbonization of this sector, we suggest three guiding principles for developing policy mixes for decarbonizing hard-to-abate sectors: (1) employ technology-specific policies but aim at broad sectoral or general policies when suitable, (2) consider value chain interdependency and user segment heterogeneity when prioritizing technologies and user segments, and (3) translate (rather than transfer) successful policies to other settings (e.g. user segments)

What it takes to measure a fundamental difference between dark matter and baryons: the halo velocity anisotropy

Numerous ongoing experiments aim at detecting WIMP dark matter particles from the galactic halo directly through WIMP-nucleon interactions. Once such a detection is established a confirmation of the galactic origin of the signal is needed. This requires a direction-sensitive detector. We show that such a detector can measure the velocity anisotropy beta of the galactic halo. Cosmological N-body simulations predict the dark matter anisotropy to be nonzero, beta~0.2. Baryonic matter has beta=0 and therefore a detection of a nonzero beta would be strong proof of the fundamental difference between dark and baryonic matter. We estimate the sensitivity for various detector configurations using Monte Carlo methods and we show that the strongest signal is found in the relatively few high recoil energy events. Measuring beta to the precision of ~0.03 will require detecting more than 10^4 WIMP events with nuclear recoil energies greater than 100 keV for a WIMP mass of 100 GeV and a 32S target. This number corresponds to ~10^6 events at all energies. We discuss variations with respect to input parameters and we show that our method is robust to the presence of backgrounds and discuss the possible improved sensitivity for an energy-sensitive detector.Comment: 15 pages, 8 figures, accepted by JCAP. Matches accepted versio

Exploring individual and work organizational peculiarities of working in emergency medical communication centers in Norway- a qualitative study

publishedVersio

Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared to CCL19 and to a C-terminal truncated (tailless) CCL21 in DCs. In contrast, tailless-CCL21 displays increased potency in DC chemotaxis compared to native CCL21. Using a CCL21-specific antibody, we show that CCL21, but not tailless-CCL21, accumulates at the cell surface. In addition removal of sialic acid from the cell surface by neuraminidase treatment impairs ERK1/2 activation by CCL21, but not of CCL19 or tailless-CCL21. Using standard laboratory cell-lines, we observe low potency of both CCL21 and tailless-CCL21 in G protein activation and -arrestin recruitment compared to CCL19, indicating that the tail itself does not improve receptor interaction. Chemokines interact with their receptors in a stepwise manner with ultimate docking of their N-terminus into the main binding pocket. Employing site-directed mutagenesis we identify residues in this pocket of selective CCL21 importance. We also identify a molecular switch in the top of TM7 important for keeping CCR7 in an inactive conformation (Tyr312), as introduction of the chemokine receptor-conserved Glu (or Ala) induces high constitutive activity. Summarized, we show that the interaction of the tail of CCL21 with polysialic acid is needed for strong ERK-signaling, whereas it impairs CCL21-mediated chemotaxis and has no impact on receptor docking consistent with the current model of chemokine:receptor interaction. This indicates that future selective pharmacological targeting of CCL19 versus CCL21 should focus on a differential targeting of the main receptor pocket, while selective targeting of tailless-CCL21 versus CCL21 and CCL19 requires targeting of the glycosaminoglycan (GAG) interaction

Promising Tools in Prostate Cancer Research:Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC(50) values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells

A novel suture method to place and adjust peripheral nerve catheters

We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in‐plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging