421 research outputs found
Mechanisms of Peptide Oxidation by Hydroxyl Radicals: Insight at the Molecular Scale
Molecular dynamics (MD) simulations were performed to provide atomic scale insight in the initial interaction between hydroxyl radicals (OH) and peptide systems in solution. These OH radicals are representative reactive oxygen species produced by cold atmospheric plasmas. The use of plasma for biomedical applications is gaining increasing interest, but the fundamental mechanisms behind the plasma modifications still remain largely elusive. This study helps to gain more insight in the underlying mechanisms of plasma medicine but is also more generally applicable to peptide oxidation, of interest for other applications. Combining both reactive and nonreactive MD simulations, we are able to elucidate the reactivity of the amino acids inside the peptide systems and their effect on their structure up to 1 μs. Additionally, experiments were performed, treating the simulated peptides with a plasma jet. The computational results presented here correlate well with the obtained experimental data and highlight the importance of the chemical environment for the reactivity of the individual amino acids, so that specific amino acids are attacked in higher numbers than expected. Furthermore, the long time scale simulations suggest that a single oxidation has an effect on the 3D conformation due to an increase in hydrophilicity and intra- and intermolecular interactions
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
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
Constraining interactions mediated by axion-like particles with ultracold neutrons
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 Hg atoms confined in the same volume. The
measurement was performed in a 1 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 . 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 m
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
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)
Revised experimental upper limit on the electric dipole moment of the neutron
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.)
Gravitational depolarization of ultracold neutrons: comparison with data
We compare the expected effects of so-called gravitationally enhanced depolarization of ultracold neutrons to measurements carried out in a spin-precession chamber exposed to a variety of vertical magnetic-field gradients. In particular, we have investigated the dependence upon these field gradients of spin-depolarization rates and also of shifts in the measured neutron Larmor precession frequency. We find excellent qualitative agreement, with gravitationally enhanced depolarization accounting for several previously unexplained features in the data
Measurement of double beta decay of ¹⁰⁰Mo to excited states in the NEMO 3 experiment
The double beta decay of ¹⁰⁰Mo to the 0_{1}^{+} and 2_{1}^{+} excited states of ¹⁰⁰Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of ¹⁰⁰Mo to the excited 0_{1}^{+} state is measured to be T_{1/2}^{2v} = [5.7_{-0.9}^{+1.3} (stat.) ± 0.8 (syst.)] x 10²⁰ y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0_{1}^{+} state has been found. The corresponding half-life limit is T_{1/2}^{0v} (0⁺→0_{1}^{+}) > 8.9 x 10²² y (at 90% C.L.). The search for the double beta decay to the 2_{1}^{+} excited state has allowed the determination of limits on the half-life for the two neutrino mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.1 x 10²¹ y (at 90% C.L.) and for the neutrinoless mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.6 x 10²³ y (at 90% C.L.)
Testing isotropy of the universe using the Ramsey resonance technique on ultracold neutron spins
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
First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula
The Vela supernova remnant (SNR) is a complex region containing a number of
sources of non-thermal radiation. The inner section of this SNR, within 2
degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray
atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from
an extended region to the south of the pulsar, within an integration region of
radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36'
J2000.0). The excess coincides with a region of hard X-ray emission seen by the
ROSAT and ASCA satellites. The observed energy spectrum of the source between
550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45
+/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/-
2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17
(stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear
measurement of a peak in the spectral energy distribution from a VHE gamma-ray
source, likely related to inverse Compton emission. A fit of an Inverse Compton
model to the H.E.S.S. spectral energy distribution gives a total energy in
non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a
distance of 290 parsec to the pulsar. The best fit electron power law index is
2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and
Astrophysics letter
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