Localization of Human RNase Z Isoforms: Dual Nuclear/Mitochondrial Targeting of the ELAC2 Gene Product by Alternative Translation Initiation

RNase Z is an endonuclease responsible for the removal of 3′ extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase ZL) encoded by ELAC2, and a short form (RNase ZS; ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase ZS was found in the cytosol, whereas RNase ZL localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase ZL. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase ZL is the enzyme involved in both, nuclear and mitochondrial tRNA 3′ end maturation

A Novel Optical Beam Concept for Producing Coherent Synchrotron Radiation with Large Energy Spread Beams

Up to now two FEL concepts are known in conventional accelerators: 1.) In THz lasers an off-crest cavity adds a chirp to the bunch followed by a bunch compressor. Particles with different energies travel on different trajectories to the radiator. 2.) For EUV and X-ray FELs the beam enters an undulator which produces microbunches which then radiate. In this paper it is proposed to copy the THz laser scheme for EUV lasers. The incoming beam is chirped and a dogleg forces afterwards the particles with different energies to move on different parallel trajectories. Considering a detector plane perpendicular to the trajectories the particles with different energies arrive in general at different times. When in this plane for instance a TGU (Transverse Gradient Undulator) is positioned the emitted radiation in the TGU is monochromatic. If in addition chirp and dogleg are selected in such a way that the particles with different energies arrive at the same time at the entrance of the TGU the radiation is monochromatic and coherent similar to the THz laser concept

Beam position measurement in the CEBAF recirculating linacs by use of pseudorandom pulse sequences

The recirculating linear accelerator at CEBAF presents unique problems in beam position measurement. As many as five beams with different energies may be simultaneously in the linac. Modulation of the beam intensity by pseudorandom pulse sequences offers a simple, effective method for distinguishing between the individual beamlets

Magnetic Characterization of a Superconducting Transverse Gradient Undulator for Compact Laser Wakefield Accelerator-Driven FELs

A transverse gradient undulator (TGU) is a key component compensating for the relatively large energy spread of Laser Wakefield Accelerator (LWFA)-generated electron beams for realizing a compact Free Electron Laser (FEL). A superconducting TGU with 40 periods has been fabricated at the Karlsruhe Institute of Technology (KIT). In this contribution, we report that the superconducting TGU has been commissioned with nominal operational parameters at an off-line test bench. An experimental set-up for mapping the magnetic field on a two-dimensional grid in the TGU gap has been employed for the magnetic characterization. We show the first preliminary results of these measurements showing the longitudinal quality, the transverse gradient and the transient behaviour of the superconducting TGU field

FLUTE, a linac based THz source

We propose a versatile THz source named FLUTE (Ferninfrarot Linac- Und Test-Experiment) based on a 30 - 50 MeV S-band linac with bunch compressor, that aimsat not only producing high field THz pulses but also at serving as a test facility to study accelerator physics issues. This source is an important step towards the planned ultra-broadband THz to mid infrared user facility TBONE. Special emphasis is put on studies of bunch compression as a function of bunch charge (0.1-5 nC) and of different generation mechanisms of coherent radiation (CSR, CER, CTR). This paper describes the design and layout of the proposed FLUTE machine and presents results of beam dynamic calculations with the tracking programs ASTRA and CSRtrack. In addition, calculations for the achievable peak electrical field and spectral characteristics for one version of the FLUTE layout are shown

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

Радиографический метод контроля сварных швов трубопроводов

Обнаружение дефектов сварных соединений является одной из основных задач неразрушающего контроля, применяемого для диагностики технического состояния трубопроводов различного назначения. Среди методов неразрушающего контроля широкое распространение получил радиографический метод. Для обработки изображений, полученных радиографическим методом, и обнаружения дефектов сварки, используются различные алгоритмы. Одним из перспективных алгоритмов обработки изображений является алгоритм, основанный на методе нейронной сети.Detection of defects in welded joints is one of the main tasks of non-destructive testing used for diagnostics of the technical condition of pipelines for various purposes. Among the methods of nondestructive testing, the radiographic method is widely used. For processing images obtained by radiographic method, and the detection of welding defects, various algorithms are used. One of the promising algorithms for image processing is an algorithm based on the neural network method

Effectiveness and acceptability of progestogens in combined oral contraceptives – a systematic review

BACKGROUND: The progestogen component of oral contraceptives (OCs) has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. METHODS: The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. RESULTS: Twenty–two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first–generation (RR 0.79; 95% CI 0.69–0.91). Cycle control appeared to be better with second-compared to first-generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52–0.91) and (RR 0.61; 95% CI 0.43–0.85), respectively. Intermenstrual bleeding was less with third- compared to second-generation pills (RR 0.71; 95% CI 0.55–0.91). Contraceptive effectiveness of gestodene (GSD) was comparable to that of levonorgestrel (LNG), and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding). Drospirenone (DRSP) was similar compared to desogestrel (DSG) regarding contraceptive effectiveness, cycle control and side effects. CONCLUSION: The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also comparable to DSG. DRSP is comparable to DSG. Future research should focus on independently conducted well designed randomized trials comparing particularly the third- with second-generation progestogens