414 research outputs found

    Apostasy & Islamic Civil Society in Malaysia

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    In Malaysia, legal definitions of the religious category “Muslim” and ethnic category “Malay” imply each other. Consequently, Muslims who have renounced Islam find themselves in an abyssal legal zone. The legal intricacies and the media representations surrounding apostasy reveal tensions between “the secular” and “the religious,” thereby providing insight into the imbalanced and bifurcated nature of civil society in Malaysia

    Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study

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    The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor

    Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers

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    Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small molecules, two (or even more) ions with identical sum formula and mass, but distinct drift times are observed. In spite of showing their own unique and characteristic fragmentation spectra in MS/MS, no configurational or constitutional isomers are found to be present in solution. Instead the observation and separation of such ions appears to be inherent to their gas-phase behaviour during ion mobility experiments. The origin of multiple drift times is thought to be the result of protonation site isomers ('protomers'). Although some important properties of protomers have been highlighted by other studies, correlating the experimental collision cross-sections (CCSs) with calculated values has proven to be a major difficulty. As a model, this study uses the pharmaceutical compound melphalan and a number of related molecules with alternative (gas-phase) protonation sites. Our study combines density functional theory (DFT) calculations with modified MobCal methods (e.g. nitrogen-based Trajectory Method algorithm) for the calculation of theoretical CCS values. Calculated structures can be linked to experimentally observed signals, and a strong correlation is found between the difference of the calculated dipole moments of the protomer pairs and their experimental CCS separation

    Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): Protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations

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    Introduction: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. Methods and analysis: The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. Ethics and dissemination: Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. Results: Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. Trial registration number: This study is registered at Clinicaltrials.gov (NCT02013076)

    Constraining interactions mediated by axion-like particles with ultracold neutrons

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    We report a new limit on a possible short range spin-dependent interaction from the precise measurement of the ratio of Larmor precession frequencies of stored ultracold neutrons and 199^{199}Hg atoms confined in the same volume. The measurement was performed in a \sim1μ\mu T vertical magnetic holding field with the apparatus searching for a permanent electric dipole moment of the neutron at the Paul Scherrer Institute. A possible coupling between freely precessing polarized neutron spins and unpolarized nucleons of the wall material can be investigated by searching for a tiny change of the precession frequencies of neutron and mercury spins. Such a frequency change can be interpreted as a consequence of a short range spin-dependent interaction that could possibly be mediated by axions or axion-like particles. The interaction strength is proportional to the CP violating product of scalar and pseudoscalar coupling constants gSgPg_Sg_P. Our result confirms limits from complementary experiments with spin-polarized nuclei in a model-independent way. Limits from other neutron experiments are improved by up to two orders of magnitude in the interaction range of 106<λ<10410^{-6}<\lambda<10^{-4} m

    Discovery of an X-ray nebula around PSR J1718-3825 and implications for the nature of the gamma-ray source HESS J1718-385

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    Combined X-ray synchrotron and inverse-Compton gamma-ray observations of pulsar wind nebulae (PWN) may help to elucidate the processes of acceleration and energy loss in these systems. In particular, such observations provide constraints on the particle injection history and the magnetic field strength in these objects. The newly discovered TeV gamma-ray source HESS J1718-385 has been proposed as the likely PWN of the high spin-down luminosity pulsar PSR J1718-3825. The absence of previous sensitive X-ray measurements of this pulsar, and the unusual energy spectrum of the TeV source, motivated observations of this region with XMM-Newton. The data obtained reveal a hard spectrum X-ray source at the position of PSR 1718-3825 and evidence for diffuse emission in the vicinity of the pulsar. We derive limits on the keV emission from the centroid of HESS J1718-385 and discuss the implications of these findings for the PWN nature of this object.Comment: 4 pages, 2 figures, submitted to A&

    Testing isotropy of the universe using the Ramsey resonance technique on ultracold neutron spins

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    Physics at the Planck scale could be revealed by looking for tiny violations of fundamental symmetries in low energy experiments. In 2008, a sensitive test of the isotropy of the Universe using has been performed with stored ultracold neutrons (UCN), this is the first clock-comparison experiment performed with free neutrons. During several days we monitored the Larmor frequency of neutron spins in a weak magnetic field using the Ramsey resonance technique. An non-zero cosmic axial field, violating rotational symmetry, would induce a daily variation of the precession frequency. Our null result constitutes one of the most stringent tests of Lorentz invariance to date.Comment: proceedings of the PNCMI2010 conferenc

    Revised experimental upper limit on the electric dipole moment of the neutron

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    We present for the first time a detailed and comprehensive analysis of the experimental results that set the current world sensitivity limit on the magnitude of the electric dipole moment (EDM) of the neutron. We have extended and enhanced our earlier analysis to include recent developments in the understanding of the effects of gravity in depolarizing ultracold neutrons; an improved calculation of the spectrum of the neutrons; and conservative estimates of other possible systematic errors, which are also shown to be consistent with more recent measurements undertaken with the apparatus. We obtain a net result of dn=−0.21±1.82×10−26  e cm, which may be interpreted as a slightly revised upper limit on the magnitude of the EDM of 3.0×10−26  e cm (90% C.L.) or 3.6×10−26  e cm (95% C.L.)
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