Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections

Background. Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry. Methods. Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes. Results. The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice. Conclusions. We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation

Annihilation of low energy antiprotons in silicon

The goal of the AE$\mathrm{\bar{g}}$IS experiment at the Antiproton Decelerator (AD) at CERN, is to measure directly the Earth's gravitational acceleration on antimatter. To achieve this goal, the AE$\mathrm{\bar{g}}$IS collaboration will produce a pulsed, cold (100 mK) antihydrogen beam with a velocity of a few 100 m/s and measure the magnitude of the vertical deflection of the beam from a straight path. The final position of the falling antihydrogen will be detected by a position sensitive detector. This detector will consist of an active silicon part, where the annihilations take place, followed by an emulsion part. Together, they allow to achieve 1$$ precision on the measurement of $\bar{g}$ with about 600 reconstructed and time tagged annihilations. We present here, to the best of our knowledge, the first direct measurement of antiproton annihilation in a segmented silicon sensor, the first step towards designing a position sensitive silicon detector for the AE$\mathrm{\bar{g}}$IS experiment. We also present a first comparison with Monte Carlo simulations (GEANT4) for antiproton energies below 5 MeVComment: 21 pages in total, 29 figures, 3 table

Prospects for measuring the gravitational free-fall of antihydrogen with emulsion detectors

The main goal of the AEgIS experiment at CERN is to test the weak equivalence principle for antimatter. AEgIS will measure the free-fall of an antihydrogen beam traversing a moir\'e deflectometer. The goal is to determine the gravitational acceleration g for antihydrogen with an initial relative accuracy of 1% by using an emulsion detector combined with a silicon micro-strip detector to measure the time of flight. Nuclear emulsions can measure the annihilation vertex of antihydrogen atoms with a precision of about 1 - 2 microns r.m.s. We present here results for emulsion detectors operated in vacuum using low energy antiprotons from the CERN antiproton decelerator. We compare with Monte Carlo simulations, and discuss the impact on the AEgIS project.Comment: 20 pages, 16 figures, 3 table

A Review of the Occurrence of Bats (Chiroptera) on Islands in the North East Atlantic and on North Sea Installations

The bats recorded from Iceland, the Faroe Islands, the Shetland Islands, the Orkney Islands, and North Sea installations are reviewed to the end of 2012. In total 12 species have been positively identified, while a considerable proportion of all records are sightings of unidentified bats. Eight of the species are European in origin and four originate from the New World. The largest number of species (8) has been recorded in Iceland, but the greatest number of individuals (180) has been found in Orkney. The bat invasion on the Faroe Islands in 2010 is without precedence, when 70 observations of a minimum of 45 individuals were noted. Most bat observations in the study area occurred in the autumn, with fewer in the spring. Most observations were of single animals, but there were also sightings of up to 12 individuals. There has been a marked increase in bat records in the past three decades. We discuss whether this is a real increase, or due to improved communications, increased public awareness, increased shipping, changes in weather patterns and/or the effects of climate change. All factors appear to be involved.© Museum and Institute of Zoology PAS. The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

A Moiré Deflectometer for Antimatter

The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics - the moirè deflectometer - for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter

AEgIS Experiment: Measuring the Acceleration g of the Earth's Gravitational Field on Antihydrogen Beam

The AEgIS experiment [1] aims at directly measuring the gravitational acceleration g on a beam of cold antihydrogen (H) to a precision of 1%, performing the first test with antimatter of the (WEP) Weak Equivalence Principle. The experimental apparatus is sited at the Antiproton Decelerator (AD) at CERN, Geneva, Switzerland. After production by mixing of antiprotons with Rydberg state positronium atoms (Ps), the atoms will be driven to fly horizontally with a velocity of a few 100 ms−1 for a path length of about 1 meter. The small deflection, few tens of μm, will be measured using two material gratings (of period ∼ 80 μm) coupled to a position-sensitive detector working as a moiré deflectometer similarly to what has been done with matter atoms [2]. The shadow pattern produced by the beam will then be detected by reconstructing the annihilation points with a spatial resolution (∼ 2 μm) of each antiatom at the end of the flight path by the sensitive-position detector. During 2012 the experimental apparatus has been commissioned with antiprotons and positrons. Since the AD will not be running during 2013,during the refurbishment of the CERN accelerators, the experiment is currently working with positrons, electrons and protons, in order to prepare the way for the antihydrogen production in late 2014

Bats Avoid Radar Installations: Could Electromagnetic Fields Deter Bats from Colliding with Wind Turbines?

Large numbers of bats are killed by collisions with wind turbines, and there is at present no direct method of reducing or preventing this mortality. We therefore determine whether the electromagnetic radiation associated with radar installations can elicit an aversive behavioural response in foraging bats. Four civil air traffic control (ATC) radar stations, three military ATC radars and three weather radars were selected, each surrounded by heterogeneous habitat. Three sampling points matched for habitat type and structure, dominant vegetation species, altitude and surrounding land class were located at increasing distances from each station. A portable electromagnetic field meter measured the field strength of the radar at three distances from the source: in close proximity (<200 m) with a high electromagnetic field (EMF) strength >2 volts/metre, an intermediate point within line of sight of the radar (200–400 m) and with an EMF strength <2 v/m, and a control site out of sight of the radar (>400 m) and registering an EMF of zero v/m. At each radar station bat activity was recorded three times with three independent sampling points monitored on each occasion, resulting in a total of 90 samples, 30 of which were obtained within each field strength category. At these sampling points, bat activity was recorded using an automatic bat recording station, operated from sunset to sunrise. Bat activity was significantly reduced in habitats exposed to an EMF strength of greater than 2 v/m when compared to matched sites registering EMF levels of zero. The reduction in bat activity was not significantly different at lower levels of EMF strength within 400 m of the radar. We predict that the reduction in bat activity within habitats exposed to electromagnetic radiation may be a result of thermal induction and an increased risk of hyperthermia

Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients

The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation

Measuring the gravitational free-fall of antihydrogen

Antihydrogen holds the promise to test, for the first time, the universality of free-fall with a system composed entirely of antiparticles. The AEgIS experiment at CERN's antiproton decelerator aims to measure the gravitational interaction between matter and antimatter by measuring the deflection of a beam of antihydrogen in the Earths gravitational field ( g ¯ $\overline {\textrm {g}}$ ). The principle of the experiment is as follows: cold antihydrogen atoms are synthesized in a Penning-Malberg trap and are Stark accelerated towards a moiré deflectometer, the classical counterpart of an atom interferometer, and annihilate on a position sensitive detector. Crucial to the success of the experiment is the spatial precision of the position sensitive detector. We propose a novel free-fall detector based on a hybrid of two technologies: emulsion detectors, which have an intrinsic spatial resolution of 50 nm but no temporal information, and a silicon strip / scintillating fiber tracker to provide timing and positional information. In 2012 we tested emulsion films in vacuum with antiprotons from CERN's antiproton decelerator. The annihilation vertices could be observed directly on the emulsion surface using the microscope facility available at the University of Bern. The annihilation vertices were successfully reconstructed with a resolution of 1-2 μmon the impact parameter. If such a precision can be realized in the final detector, Monte Carlo simulations suggest of order 500 antihydrogen annihilations will be sufficient to determine g ¯ $\overline {\textrm {g}}$ with a 1 % accuracy. This paper presents current research towards the development of this technology for use in the AEgIS apparatus and prospects for the realization of the final detector