517 research outputs found
Cystatins as calpain inhibitors: Engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of μ-calpain
Within the cystatin superfamily, only kininogen domain 2 (KD2) is able to inhibit μ- and m-calpain. In an attempt to elucidate the structural requirements of cystatins for calpain inhibition, we constructed recombinant hybrids of human stefin B (an intracellular family 1 cystatin) with KD2 and Delta L110 deletion mutants of chicken cystatin-KD2 hybrids. Substitution of the N-terminal contact region of stefin B by the corresponding KD2 sequence resulted in a calpain inhibitor of K-i = 188 nM. Deletion of L110, which forms a beta -bulge in family 1 and 2 cystatins but is lacking in KD2, improved inhibition of mu -calpain 4- to 8-fold. All engineered cystatins were temporary inhibitors of calpain due to slow substrate-like cleavage of a single peptide bond corresponding to Gly9-Ala10 in chicken cystatin. Biomolecular interaction analysis revealed that, unlike calpastatin, the cystatin-type inhibitors do not bind to the calmodulin-like domain of the small subunit of calpain, and their interaction with the mu -calpain heterodimer is completely prevented by a synthetic peptide comprising subdomain B of calpastatin domain 1. Based on these results we propose that (i) cystatin-type calpain inhibitors interact with the active site of the catalytic domain of calpain in a similar cystatin-like mode as with papain and (ii) the potential for calpain inhibition is due to specific subsites within the papain-binding regions of the general cystatin fold
Women's knowledge of maternal danger signs during pregnancy: Findings from a cross-sectional survey in Papua New Guinea
© 2019 Objective: To explore knowledge of pregnancy related danger signs among women attending antenatal clinics in Papua New Guinea. Design: Cross-sectional survey undertaken as part of a wider integrated health and demographic survey. Setting: Three sites in Papua New Guinea: Hiri District (Central Province), Karkar (Madang Province) and Asaro (Eastern Highlands Province). Participants: 482 women aged 15–44 years. Findings: Almost all (95.2%; 459/482) women attended for antenatal care at least once; 68.2% attended four or more times. Among women who attended the antenatal clinic, 53.6% (246/459) reported receiving information about danger signs in pregnancy from a health worker. Of these 60.2% (148/246) could recall at least one danger sign. In addition, 16.4% (35/213) of women who did not receive information from the antenatal clinic reported pregnancy related danger signs. Among the 183 women who reported danger signs, 47.5% (87/183) reported fever; 39.3% (72/183) reported vaginal bleeding and 36.6% (67/183) reported swelling of the face, legs and arms. Women who reported receiving information at the antenatal clinic were significantly more likely know any danger signs, compared with women who did not receive information at the antenatal clinic (OR 7.68 (95%CI: 4.93, 11.96); p = <0.001). Knowledge of danger signs was significantly associated with secondary school education, compared with none or only primary education (OR 3.08 (95% CI: 2.06, 4.61); p = <0.001). Conclusions and implications for practice: Every antenatal clinic visit should be used opportunistically to provide women with information about key danger signs during pregnancy and childbirth. Recognising maternal danger signs, together with the importance of seeking early transfer to the health facility and the importance of attending for a health facility birth are critical to improving outcomes for mothers and babies especially in low income settings such as Papua New Guinea
Chiral magnetization textures stabilized by the Dzyaloshinskii-Moriya interaction during spin-orbit torque switching
We study the effect of the Dzyaloshinskii-Moriya interaction (DMI) on
current-induced magnetic switching of a perpendicularly magnetized
heavy-metal/ferromagnet/oxide trilayer both experimentally and through
micromagnetic simulations. We report the generation of stable helical
magnetization stripes for a sufficiently large DMI strength in the switching
region, giving rise to intermediate states in the magnetization confirming the
essential role of the DMI on switching processes. We compare the simulation and
experimental results to a macrospin model, showing the need for a micromagnetic
approach. The influence of the temperature on the switching is also discussed.Comment: Includes corrected acknowledgements and clarification of simulation
parameter
Emission pathways to achieve 2.0°C and 1.5°C climate targets
We investigated the feasibilities of 2.0°C and 1.5°C climate targets by considering the abatement potentials of a full suite of greenhouse gases, pollutants, and aerosols. We revised the inter-temporal dynamic optimization model DICE-2013R by introducing three features as follows. First, we applied a new marginal abatement cost curve derived under moderate assumptions regarding future socioeconomic development—the Shared Socioeconomic Pathways 2 (SSP2) scenario. Second, we addressed emission abatement for not only industrial CO2 but also land-use CO2, CH4, N2O, halogenated gases, CO, volatile organic compounds, SOx, NOx, black carbon and organic carbon. Third, we improved the treatment of the non-CO2 components in the climate module based on MAGICC 6.0. We obtained the following findings: (1) It is important to address the individual emissions in an analysis of low stabilization scenarios because abating land-use CO2, non-CO2 and aerosol emissions also contributes to maintaining a low level of radiative forcing and substantially affects the climate costs. (2) The 2.0°C target can be efficiently reached under the assumptions of the SSP2 scenario. (3) The 1.5°C target can be met with early deep cuts under the assumption of a temperature overshoot, and it will triple the carbon price and double the mitigation cost compared with the 2.0°C case
Electron-phonon relaxation and excited electron distribution in zinc oxide and anatase
We propose a first-principle method for evaluations of the time-dependent
electron distribution function of excited electrons in the conduction band of
semiconductors. The method takes into account the excitations of electrons by
external source and the relaxation to the bottom of conduction band via
electron-phonon coupling. The methods permits calculations of the
non-equilibrium electron distribution function, the quasi-stationary
distribution function with steady-in-time source of light, the time of setting
of the quasi-stationary distribution and the time of energy loss via relaxation
to the bottom of conduction band. The actual calculations have been performed
for titanium dioxide in the anatase structure and zinc oxide in the wurtzite
structure. We find that the quasi-stationary electron distribution function for
ZnO is a fermi-like curve that rises linearly with increasing excitation energy
whereas the analogous curve for anatase consists of a main peak and a shoulder.
The calculations demonstrate that the relaxation of excited electrons and the
setting of the quasi-stationary distribution occur within the time no more than
500 fsec for ZnO and 100 fsec for anatase.
We also discuss the applicability of the effective phonon model with
energy-independent electron-phonon transition probability. We find that the
model only reproduces the trends in changing of the characteristic times
whereas the precision of such calculations is not high. The rate of energy
transfer to phonons at the quasi-stationary electron distribution also have
been evaluated and the effect of this transfer on the photocatalyses has been
discussed. We found that for ZnO this rate is about 5 times less than in
anatase.Comment: 21 p., 9 figure
Highly Enantioselective Conjugate Addition of Thiols using Mild Scandium Triflate Catalysis
Purification of two distinct types of phosphoinositide-specific phospholipase C from rat liver. Enzymological and structural studies
Tpeak-Tend, Tpeak-Tend/QT ratio and Tpeak-Tend dispersion for risk stratification in Brugada Syndrome:A systematic review and meta-analysis
Background: Brugada syndrome is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF), potentially leading to sudden cardiac death (SCD). Tpeak-Tend intervals, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion have been proposed for risk stratification, but their predictive values in Brugada syndrome have been challenged recently. Methods: A systematic review and meta-analysis was conducted to examine their values in predicting arrhythmic and mortality outcomes in Brugada Syndrome. PubMed and Embase databases were searched until 1 May 2018, identifying 29 and 57 studies. Results: Nine studies involving 1740 subjects (mean age 45 years old, 80% male, mean follow-up duration was 68 ± 27 months) were included. The mean Tpeak-Tend interval was 98.9 ms (95% CI: 90.5-107.2 ms) for patients with adverse events (ventricular arrhythmias or SCD) compared to 87.7 ms (95% CI: 80.5-94.9 ms) for those without such events, with a mean difference of 11.9 ms (95% CI: 3.6-20.2 ms, P = 0.005; I2 = 86%). Higher (Tpeak-Tend)/QT ratios (mean difference = 0.019, 95% CI: 0.003-0.036, P = 0.024; I2 = 74%) and Tpeak-Tend dispersion (mean difference = 7.8 ms, 95% CI: 2.1-13.4 ms, P = 0.007; I2 = 80%) were observed for the event-positive group. Conclusion: Tpeak-Tend interval, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion were higher in high-risk than low-risk Brugada subjects, and thus offer incremental value for risk stratification
Observation of Coherently Coupled Cation Spin Dynamics in an Insulating Ferrimagnetic Oxide
Many technologically useful magnetic oxides are ferrimagnetic insulators,
which consist of chemically distinct cations. Here, we examine the spin
dynamics of different magnetic cations in ferrimagnetic NiZnAl-ferrite
(NiZnAlFeO) under continuous microwave
excitation. Specifically, we employ time-resolved x-ray ferromagnetic resonance
to separately probe Fe and Ni cations on different sublattice
sites. Our results show that the precessing cation moments retain a rigid,
collinear configuration to within 2. Moreover, the effective
spin relaxation is identical to within 10% for all magnetic cations in the
ferrite. We thus validate the oft-assumed ``ferromagnetic-like'' dynamics in
resonantly driven ferrimagnetic oxides, where the magnetic moments from
different cations precess as a coherent, collective magnetization
Room temperature chiral magnetic skyrmion in ultrathin magnetic nanostructures
Magnetic skyrmions are chiral spin structures with a whirling configuration.
Their topological properties, nanometer size and the fact that they can be
moved by small current densities have opened a new paradigm for the
manipulation of magnetisation at the nanoscale. To date, chiral skyrmion
structures have been experimentally demonstrated only in bulk materials and in
epitaxial ultrathin films and under external magnetic field or at low
temperature. Here, we report on the observation of stable skyrmions in
sputtered ultrathin Pt/Co/MgO nanostructures, at room temperature and zero
applied magnetic field. We use high lateral resolution X-ray magnetic circular
dichroism microscopy to image their chiral N\'eel internal structure which we
explain as due to the large strength of the Dzyaloshinskii-Moriya interaction
as revealed by spin wave spectroscopy measurements. Our results are
substantiated by micromagnetic simulations and numerical models, which allow
the identification of the physical mechanisms governing the size and stability
of the skyrmions.Comment: Submitted version. Extended version to appear in Nature
Nanotechnolog
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