Magnetically doped topological insulators enable the quantum anomalous Hall effect (QAHE), which provides quantized edge states for lossless charge-transport applications1-8. The edge states are ...hosted by a magnetic energy gap at the Dirac point2, but hitherto all attempts to observe this gap directly have been unsuccessful. Observing the gap is considered to be essential to overcoming the limitations of the QAHE, which so far occurs only at temperatures that are one to two orders of magnitude below the ferromagnetic Curie temperature, TC (ref. 8). Here we use lowtemperature photoelectron spectroscopy to unambiguously reveal the magnetic gap of Mn-doped Bi2Te3, which displays ferromagnetic out-of-plane spin texture and opens up only below TC. Surprisingly, our analysis reveals large gap sizes at 1 kelvin of up to 90 millielectronvolts, which is five times larger than theoretically predicted9. Using multiscale analysis we show that this enhancement is due to a remarkable structure modification induced by Mn doping: instead of a disordered impurity system, a self-organized alternating sequence of MnBi2Te4 septuple and Bi2Te3 quintuple layers is formed. This enhances the wavefunction overlap and size of the magnetic gap10. Mn-doped Bi2Se3 (ref. 11) and Mn-doped Sb2Te3 form similar heterostructures, but for Bi2Se3 only a nonmagnetic gap is formed and the magnetization is in the surface plane. This is explained by the smaller spin-orbit interaction by comparison with Mn-doped Bi2Te3. Our findings provide insights that will be crucial in pushing lossless transport in topological insulators towards roomtemperature applications.
•How intramembrane proteases select their substrates is currently unknown.•Helix-destabilizing amino acids within transmembrane helices often facilitate cleavage.•Transmembrane helix stability does ...not distinguish substrates from non-substrates.•Mutations affecting cleavage influence transmembrane helix bending.
Intramembrane proteolysis – cleavage of proteins within the plane of a membrane – is a widespread phenomenon that can contribute to the functional activation of substrates and is involved in several diseases. Although different families of intramembrane proteases have been discovered and characterized, we currently do not know how these enzymes discriminate between substrates and non-substrates, how site-specific cleavage is achieved, or which factors determine the rate of proteolysis. Focusing on γ-secretase and rhomboid proteases, we argue that answers to these questions may emerge from connecting experimental readouts, such as reaction kinetics and the determination of cleavage sites, to the structures and the conformational dynamics of substrates and enzymes.
Summary
Background
Psoriasis is associated with higher prevalences of cardiovascular and metabolic comorbidities in adults but the relationship of age at onset and those prevalences is unknown.
...Objective
To evaluate whether the childhood onset of psoriasis (COP) is correlated with the frequency of cardiovascular and metabolic comorbidities in adulthood.
Methods
This noninterventional, cross‐sectional, multicentre study of adults with psoriasis was conducted in 29 dermatology centres in France. Data on sex, age at onset of psoriasis and its clinical characteristics, and cardiovascular risk factors, including weight, body mass index, waist circumference, dyslipidaemia, diabetes, hypertension, smoking, and personal/familial major adverse cardiovascular events (MACE) were systematically recorded.
Results
Two thousand two hundred and one patients with psoriasis (male: 56%; mean age: 49 years; 25% with COP) were included consecutively in the study. Univariate analysis showed that COP was associated with lower frequencies of obesity, high waist circumference, diabetes, dyslipidaemia, hypertension, familial cardiovascular disease, MACE and metabolic syndrome, but more frequent active smoking. Multivariate analysis retained age as being associated with frequency of cardiovascular and metabolic comorbidities, and sex with smoking, but not age at the onset of psoriasis. Psoriasis severity was associated with higher frequencies of obesity and psoriatic arthritis.
Conclusion
Our results showed that COP does not seem to be an additional risk factor for higher frequencies of cardiovascular and metabolic comorbidities during adulthood.
What's already known about this topic?
Psoriasis and its severity are associated with higher prevalence of cardiovascular and metabolic comorbidities in adults.
Childhood onset of psoriasis is not associated with obesity in adulthood.
What does this study add?
Childhood onset of psoriasis is not associated with cardiovascular and metabolic comorbidities in adulthood.
In France, as in most countries, psoriasis is associated with high frequencies of cardiovascular and metabolic comorbidities in adults.
Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify ...MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1–MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysisshowed expression of
MRP1,
MRP2,
MRP3,
MRP4, and
MRP5 mRNA, whereas
MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs.
Sprays produced by pressure atomization of various liquids are investigated experimentally, showing the self-similar flow fields of both the liquid and the gas phases. Phase-Doppler measurements are ...conducted in the sprays at varying radial and axial distances from the atomizer orifice. The theoretical description of the gas flow field based on boundary-layer theory reveals a self-similar velocity field driven by momentum transfer from the liquid phase ejected into the gaseous environment. The momentum loss of the liquid droplet phase is also found to be self-similar, which was to be expected, but not shown in the literature before. The analytical self-similar description of the two-phase flow field is in excellent agreement with the experimental data.
Through its impact on students in their lives in and beyond college, and recognizing the porous boundary between the classroom and the "real world," SoTL can offer insights into broader societal ...issues, offer evidence of activities that facilitate everyday learning, promote intrinsic motivation, better support people from underrepresented communities, or uncover the ripple effects of changing educational environments. It has the potential to deliver messages of broad public interest. This book extends the field-building work of Boyer's "Scholarship Reconsidered" and Hutchings, Huber, and Ciccone's "The Scholarship of Teaching and Learning Reconsidered" by taking a new look at SoTL's ubiquitous call to "go public." "Going Public Reconsidered" explores the potential impacts of knowledge generated by SoTL, considers its varied public audiences, and offers guidance for the appropriate media and modes of communication to reach them, including the use of social media. It urges the SoTL community to step up and contribute its expertise to conversations about the crises that face our communities, nations, and the world, and disseminate the relevance of its research for the world outside of the classroom. Recognizing that many practitioners find it difficult to conceptualize the public in public SoTL beyond the higher education audiences they routinely address, this book focusses on conceptualizing, planning, and shaping the message, and clarifying appropriate audiences. It offers guidance on the "who" and the "how" of public SoTL. "Going Public Reconsidered" addresses such questions as: What is happening in the world that would benefit from a SoTL-informed perspective? (1) What information, insight, or knowledge does SoTL generate? (2) Who beyond higher education might care about this information, insight, or knowledge, and why? and (3) How can we adapt to the venues and platforms where they currently get their information and knowledge? The fifteen editors and contributors explore the potential and the implications of extending SoTL beyond its current horizons by reflecting on the ultimate responsibility of those who profess SoTL; examining SoTL's audiences and the notion of "the public"; considering what topics and Grand Challenges public SoTL might address; offering case studies of outreach in the US and abroad; and providing guidance on the use of social media for public SoTL -- from Twitter, Facebook, LinkedIn, and YouTube to blogs -- as well as on developing relationships with mainstream media. The book's message is that public SoTL isn't a radical departure from SoTL-as-we-know-it, but a natural expansion of its methods and goals, offering the potential of broadening its impact domestically and internationally. It offers inspiration and challenges to practitioners across the globe. Foreword written by Michele DiPietro and Hillary H. Steiner.
We provide an overview and perspective on the Phase I collection and analysis of data for use in process improvement and control charting. In Phase I, the focus is on understanding the process ...variability, assessing the stability of the process, investigating process-improvement ideas, selecting an appropriate in-control model, and providing estimates of the in-control model parameters. In our article, we review and synthesize many of the important developments that pertain to the analysis of process data in Phase I. We give our view of the major issues and developments in Phase I analysis. We identify the current best practices and some opportunities for future research in this area.
We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared ...to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.
Enamel demineralisation can occur as a side effect during orthodontic treatment with fixed appliances. This study aimed to evaluate the efficacy of the self-assembling peptide P
-4 for ...remineralisation combined with fluorides, compared to application of fluoride varnish alone. De- and remineralisation was assessed by Quantitative light-induced fluorescence (QLF). Orthodontic brackets were bonded on 108 human enamel samples and white spot lesions were created. The samples were allocated randomly into three groups: Group I received no treatment, group II had a single application of fluoride varnish (22,600 ppm), and group III was treated with P
-4 following a single application of fluoride varnish. Quantitative light-induced fluorescence (QLF) measurements were performed at baseline, after demineralisation and after storage in remineralisation solution for 7 and 30 days. Non-parametric tests (Kruskal-Wallis test and Friedman test) were used for further analysis. After demineralisation, all samples showed a median ΔF -9.38% ± 2.79. After 30 days median ΔF values were as followed: group I = -9.04% ± 2.51, group II = -7.89 ± 2.07, group III = -6.08% ± 2.79). The median ΔF values differed significantly between all groups at all investigation times (p < 0.00001). Application of P
-4 with fluoride varnish was superior to the use of fluorides alone for remineralisation of enamel adjacent to brackets.
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