Hydrogen Spectroscopy with a Lamb-shift Polarimeter - An Alternative Approach Towards Anti-Hydrogen Spectroscopy Experiments

A Lamb-shift polarimeter, which has been built for a fast determination of the polarization of protons and deuterons of an atomic-beam source and which is frequently used in the ANKE experiment at COSY-J\"ulich, is shown to be an excellent device for atomic-spectroscopy measurements of metastable hydrogen isotopes. It is demonstrated that magnetic and electric dipole transitions in hydrogen can be measured as a function of the external magnetic field, giving access to the full Breit-Rabi diagram for the $2^2S_{1/2}$ and the $2^2P_{1/2}$ states. This will allow the study of hyperfine structure, $g$ factors and the classical Lamb shift. Although the data are not yet competitive with state-of-the-art measurements, the potential of the method is enormous, including a possible application to anti-hydrogen spectroscopy.Comment: 6 pages, 7 figures, accepted by European Physical Journal

Design considerations for a superconducting linac as an option for the ESS

An approach for a superconducting high-current proton linac for the ESS has been discussed as an option in the "Proposal for a Next Generation Neutron Source for Europe-the European Spallation Source (ESS)". The following work studies the technical and economic conditions for a superconducting linac at the high-energy end of the proposed accelerator system. The use of superconducting elliptical cavities for the acceleration of high-energetic particles beta =v/c-1 is certainly state of the art. This is documented by many activities (TJNAF, TESLA, LEP, LHC, and KEK). A design study for the cavities is described in another paper on this conference. For low energy particles ( beta <<1) quarter wave type cavities and spoke-type cavities have been discussed. The main motivation for this study is the expectation of significant cost reduction in terms of operational and possibly investment cost. (5 refs)

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria

Components of the death receptors-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIPL), a well- known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca2+-release as well as ER-mitochondria tethering were decreased in c-FLIP-/- mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIPL and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIPL emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4

Razvoj i biofarmaceutsko vrednovanje pripravka za povećano oslobađanje tramadol hidroklorida na principu osmotske tehnologije

Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve the same. Formulation variables like level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect the drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with performance of two commercial tablets of TRH. The developed formulation provided more prolonged and controlled TRH release as compared to marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable during 6 months of accelerated stability testing.U radu je opisana priprava i evaluacija pripravaka tramadol hidroklorida (TRH) na principu osmotske tehnologije. Da bi se postigao željeni profil oslobađanja mijenjane su različite varijable. Pokazalo se da najveći utjacaj na oslobađanje ljekovite tvari imaju udjeli polimera koji bubri, plastifikatora i debljina ovojnice polupropusne membrane (SPM). TRH oslobađanje bilo je proporcionalno udjelu plastifikatora, a obrnuto proporcionalno udjelu polimera i vrijednosti SPM. Oslobađanje ljekovite tvari bilo je neovisno o pH i intenzitetu miješanja, a ovisno o osmotskom talku medija. U in vivo studiji provedenoj na šest zdravih volontera određeni su farmakokinetički parametri (cmax, tmax, AUC0-24, MRT) i izračunata relativna bioraspoloživost. Rezultati dobiveni u pokusima in vitro i in vivo uspoređeni su s dvije vrste komercijalno dostupnih tableta TRH: oslobađanje ljekovite tvari iz pripravka razvijenog u ovom radu bilo je dulje i više kontrolirano. In vitro-in vivo korelacija (IVIVC) je analizirana prema Wagner-Nelsonovoj metodi. Optimizirani pripravak (IVB) pokazao je dobru IVIV korelaciju (R = 0,9750). Proizvodni proces je bio reproducibilan i pripravci su bili stabilni tijekom 6 mjeseci u uvjetima ubrzanog starenja

1937: Abilene Christian College Bible Lectures - Full Text

Delivered in the auditorium of Abilene Christian College, Abilene, Texas, February 193

Forward K+ production in subthreshold pA collisions at 1.0 GeV

K+ meson production in pA (A = C, Cu, Au) collisions has been studied using the ANKE spectrometer at an internal target position of the COSY-Juelich accelerator. The complete momentum spectrum of kaons emitted at forward angles, theta < 12 degrees, has been measured for a beam energy of T(p)=1.0 GeV, far below the free NN threshold of 1.58 GeV. The spectrum does not follow a thermal distribution at low kaon momenta and the larger momenta reflect a high degree of collectivity in the target nucleus.Comment: 4 pages, 3 figure

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals – a feasibility study for a randomised controlled trial

Abstract Background Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin’s effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. Methods This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18–65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. Results The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. Discussion Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash. Trial registration Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. Clinical Trial Registration Number: ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia

Mapping material stocks of buildings and mobility infrastructure in the United Kingdom and the Republic of Ireland

Understanding the size and spatial distribution of material stocks is crucial for sustainable resource management and climate change mitigation. This study presents high-resolution maps of buildings and mobility infrastructure stocks for the United Kingdom (UK) and the Republic of Ireland (IRL) at 10 m, combining satellite-based Earth observations, OpenStreetMaps, and material intensities research. Stocks in the UK and IRL amount to 19.8 Gigatons or 279 tons/cap, predominantly aggregate, concrete and bricks, as well as various metals and timber. Building stocks per capita are surprisingly similar across medium to high population density, with only the lowest population densities having substantially larger per capita stocks. Infrastructure stocks per capita decrease with higher population density. Interestingly, for a given building stock within an area, infrastructure stocks are substantially larger in IRL than in the UK. These maps can provide useful insights for sustainable urban planning and advancing a circular economy