Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

Hepatitis C Virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5´untranslated region (5´UTR), while also downstream elements like the cis-replication element (CRE) in the coding region and the 3´UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5´- and 3´-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5´end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3´UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in question acts on HCV replication when physically present in the plus strand genome or in the minus strand antigenome. Therefore, it may be required to use reduced systems that selectively focus on the analysis of HCV minus strand initiation and/or plus strand initiation

Test Results on the Silicon Pixel Detector for the TTF-FEL Beam Trajectory Monitor

Test measurements on the silicon pixel detector for the beam trajectory monitor at the free electron laser of the TESLA test facility are presented. To determine the electronic noise of detector and read-out and to calibrate the signal amplitude of different pixels the 6 keV photons of the manganese K line are used. Two different methods determine the spatial accuracy of the detector: In one setup a laser beam is focused to a straight line and moved across the pixel structure. In the other the detector is scanned using a low-intensity electron beam of an electron microscope. Both methods show that the symmetry axis of the detector defines a straight line within 0.4 microns. The sensitivity of the detector to low energy X-rays is measured using a vacuum ultraviolet beam at the synchrotron light source HASYLAB. Additionally, the electron microscope is used to study the radiation hardness of the detector.Comment: 14 pages (Latex), 13 figures (Postscript), submitted to Nuclear Instruments and Methods

Development of a thermal ionizer as ion catcher

An effective ion catcher is an important part of a radioactive beam facility that is based on in-flight production. The catcher stops fast radioactive products and emits them as singly charged slow ions. Current ion catchers are based on stopping in He and H$_2$ gas. However, with increasing intensity of the secondary beam the amount of ion-electron pairs created eventually prevents the electromagnetic extraction of the radioactive ions from the gas cell. In contrast, such limitations are not present in thermal ionizers used with the ISOL production technique. Therefore, at least for alkaline and alkaline earth elements, a thermal ionizer should then be preferred. An important use of the TRI$\mu$P facility will be for precision measurements using atom traps. Atom trapping is particularly possible for alkaline and alkaline earth isotopes. The facility can produce up to 10$^9$ s$^{-1}$ of various Na isotopes with the in-flight method. Therefore, we have built and tested a thermal ionizer. An overview of the operation, design, construction, and commissioning of the thermal ionizer for TRI$\mu$P will be presented along with first results for $^{20}$Na and $^{21}$Na.Comment: 10 pages, 4 figures, XVth International Conference on Electromagnetic Isotope Separators and Techniques Related to their Applications (EMIS 2007

"What's (the) Matter?", A Show on Elementary Particle Physics with 28 Demonstration Experiments

We present the screenplay of a physics show on particle physics, by the Physikshow of Bonn University. The show is addressed at non-physicists aged 14+ and communicates basic concepts of elementary particle physics including the discovery of the Higgs boson in an entertaining fashion. It is also demonstrates a successful outreach activity heavily relying on the university physics students. This paper is addressed at anybody interested in particle physics and/or show physics. This paper is also addressed at fellow physicists working in outreach, maybe the experiments and our choice of simple explanations will be helpful. Furthermore, we are very interested in related activities elsewhere, in particular also demonstration experiments relevant to particle physics, as often little of this work is published. Our show involves 28 live demonstration experiments. These are presented in an extensive appendix, including photos and technical details. The show is set up as a quest, where 2 students from Bonn with the aid of a caretaker travel back in time to understand the fundamental nature of matter. They visit Rutherford and Geiger in Manchester around 1911, who recount their famous experiment on the nucleus and show how particle detectors work. They travel forward in time to meet Lawrence at Berkeley around 1950, teaching them about the how and why of accelerators. Next, they visit Wu at DESY, Hamburg, around 1980, who explains the strong force. They end up in the LHC tunnel at CERN, Geneva, Switzerland in 2012. Two experimentalists tell them about colliders and our heroes watch live as the Higgs boson is produced and decays. The show was presented in English at Oxford University and University College London, as well as Padua University and ICTP Trieste. It was 1st performed in German at the Deutsche Museum, Bonn (5/'14). The show has eleven speaking parts and involves in total 20 people.Comment: 113 pages, 88 figures. An up to date version of the paper with high resolution pictures can be found at http://www.th.physik.uni-bonn.de/People/dreiner/Downloads/. In v2 the acknowledgements and a citation are correcte

Mixed Representation RPA Calculation for Octupole Excitations on Superdeformed Sates in the 40Ca and Neutron-Rich Sulfur Regions

By means of the mixed representation RPA based on the Skyrme-Hartree-Fock mean field, we investigate low-frequency octupole excitations built on the superdeformed (SD) states in the N=Z nuclei around 40Ca and the neutron-rich Sulfur isotopes. The RPA calculation is carried out fully self-consistently on the three-dimensional Cartesian mesh in a box, and yields a number of low-frequency octupole vibrations built on the SD states in 32S, 36Ar, 40Ca and 44Ti. In particular, a strongly collective K^\pi=1^- octupole vibration is suggested to appear on top of the SD state in 40Ca. For 48,50S close to the neutron drip line, we find that the low-lying state created by the excitation of a single neutron from a loosely bound low Omega level to a high Omega resonance level acquires an extremely strong octupole transition strength due to the spatially very extended structure of the particle-hole wave functions.Comment: 22 pages, 7 figure

One-dimensional Model of a Gamma Klystron

A new scheme for amplification of coherent gamma rays is proposed. The key elements are crystalline undulators - single crystals with periodically bent crystallographic planes exposed to a high energy beam of charged particles undergoing channeling inside the crystals. The scheme consists of two such crystals separated by a vacuum gap. The beam passes the crystals successively. The particles perform undulator motion inside the crystals following the periodic shape of the crystallographic planes. Gamma rays passing the crystals parallel to the beam get amplified due to interaction with the particles inside the crystals. The term `gamma klystron' is proposed for the scheme because its operational principles are similar to those of the optical klystron. A more simple one-crystal scheme is considered as well for the sake of comparison. It is shown that the gamma ray amplification in the klystron scheme can be reached at considerably lower particle densities than in the one-crystal scheme, provided that the gap between the crystals is sufficiently large.Comment: RevTeX4, 22 pages, 4 figure

Cellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profiling

Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here