Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on ...such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not ...addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg-1. A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.
The Colorado plateau is a large, tectonically intact, physiographic province in the southwestern North American Cordillera that stands at ∼1,800-2,000 m elevation and has long been thought to be in ...isostatic equilibrium. The origin of these high elevations is unclear because unlike the surrounding provinces, which have undergone significant Cretaceous-Palaeogene compressional deformation followed by Neogene extensional deformation, the Colorado plateau is largely internally undeformed. Here we combine new seismic tomography and receiver function images to resolve a vertical high-seismic-velocity anomaly beneath the west-central plateau that extends more than 200 km in depth. The upper surface of this anomaly is seismically defined by a dipping interface extending from the lower crust to depths of 70-90 km. The base of the continental crust above the anomaly has a similar shape, with an elevated Moho. We interpret these seismic structures as a continuing regional, delamination-style foundering of lower crust and continental lithosphere. This implies that Pliocene (2.6-5.3 Myr ago) uplift of the plateau and the magmatism on its margins are intimately tied to continuing deep lithospheric processes. Petrologic and geochemical observations indicate that late Cretaceous-Palaeogene (∼90-40 Myr ago) low-angle subduction hydrated and probably weakened much of the Proterozoic tectospheric mantle beneath the Colorado plateau. We suggest that mid-Cenozoic (∼35-25 Myr ago) to Recent magmatic infiltration subsequently imparted negative compositional buoyancy to the base and sides of the Colorado plateau upper mantle, triggering downwelling. The patterns of magmatic activity suggest that previous such events have progressively removed the Colorado plateau lithosphere inward from its margins, and have driven uplift. Using Grand Canyon incision rates and Pliocene basaltic volcanism patterns, we suggest that this particular event has been active over the past ∼6 Myr.
Volcanic activity at convergent plate margins is localized along lineaments of active volcanoes that focus rising magma generated within the mantle below. In many arcs worldwide, particularly ...continental arcs, the volcanic front migrates away from the interface of subduction (the trench) over millions of years, reflecting coevolving surface forcing, tectonics, crustal magma transport, and mantle flow. Here we show that extraction of melt from arc mantle and subsequent magmatic thickening of overlying crust and lithosphere can drive volcanic front migration. These processes are consistent with geochemical trends, such as increasing La/Yb, which show that increasing depths of differentiation correlate with arc front migration in continental arcs. Such thickening truncates the underlying mantle flow field, squeezing hot mantle wedge and the melting focus away from the trench while progressively decreasing the volume of melt generated. However, if magmatic thickening is balanced by tectonic extension in the upper plate, a steady crustal thickness is achieved that results in a more stationary arc front with long‐lived mantle melting. This appears to be the case for some island arcs. Thus, in combination with tectonic modulation of crustal thickness, magmatic thickening provides a self consistent model for volcanic arc front migration and the composition of arc magmas.
Key Points
Arc front migration occurs globally in continental and some oceanic settings
Crustal thickening causes arc front migration and truncates mantle melting
Tectonic extension may balance crustal thickening for stationary arc fronts
The slow kinetics of the oxygen evolution reaction (OER) is the main cause of energy loss in many low-temperature energy storage techniques, such as metal–air batteries and water splitting. A better ...understanding of both the OER mechanism and the degradation mechanism on different transition metal (TM) oxides is critical for the development of the next generation of oxides as OER catalysts. In this paper, we systematically investigated the catalytic mechanism and lifetime of ABO3−δ perovskite catalysts for the OER, where A = Sr or Ca and B = Fe or Co. During the OER process, the Fe-based AFeO3−δ oxides with δ ≈ 0.5 demonstrate no activation of lattice oxygen or pH dependence of the OER activity, which is different from the SrCoO2.5 with similar oxygen 2p-band position relative to the Fermi level. The difference was attributed to the larger changes in the electronic structure during the transition from the oxygen-deficient brownmillerite structure to the fully oxidized perovskite structure and the poor conductivity in Fe-based oxides, which hinders the uptake of oxygen from the electrolyte to the lattice under oxidative potentials. The low stability of Fe-based perovskites under OER conditions in a basic electrolyte also contributes to the different OER mechanism compared with the Co-based perovskites. This work reveals the influence of TM composition and electronic structure on the catalytic mechanism and operational stability of the perovskite OER catalysts.
Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aβ42 are established biomarkers for Alzheimer’s disease (AD) and have been used as quantitative traits for genetic ...analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10−9 for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10−8 and p = 3.22 × 10−9 for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10−8 for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10−4, 0.039, 4.86 × 10−5, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci.
► CSF tau and ptau levels provide more statistical power than case-control studies ► CSF tau levels as endophenotype for AD identified four loci implicated on AD
Cruchaga et al. use cerebrospinal fluid (CSF) tau levels as a quantitative trait for genetic studies of Alzheimer disease (AD). A genome-wide association study in over 1,200 individuals identifies genes that influence CSF tau levels and risk for AD.
Monolayer transition metal dichalcogenides are materials with an atomic structure complementary to graphene but diverse properties, including direct energy bandgaps, which makes them intriguing ...candidates for optoelectronic devices. Various approaches have been demonstrated for the growth of molybdenum disulphide (MoS2) on insulating substrates, but to date, growth of isolated crystalline flakes has been demonstrated at random locations only. Here we use patterned seeds of molybdenum source material to grow flakes of MoS2 at predetermined locations with micrometre-scale resolution. MoS2 flakes are predominantly monolayers with high material quality, as confirmed by atomic force microscopy, transmission electron microscopy and Raman and photoluminescence spectroscopy. As the monolayer flakes are isolated at predetermined locations, transistor fabrication requires only a single lithographic step. Device measurements exhibit carrier mobility and on/off ratio that exceed 10 cm(2) V(-1) s(-1) and 10(6), respectively. The technique provides a path for in-depth physical analysis of monolayer MoS2 and fabrication of MoS2-based integrated circuits.
Tourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism ...spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum.
Investigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers).
As previously identified, a common unifying factor connects TS, ADHD, and ASD, while TS and OCD show the highest genetic correlation in pairwise testing among these disorders. Thanks to a more homogeneous set of disorders and a targeted approach that is guided by genetic correlations, we were able to identify multiple novel hits and regions that seem to play a pleiotropic role for the specific disorders analyzed here and could not be identified through previous studies. In the TS-ADHD-ASD genome-wide association study single nucleotide polymorphism–based and gene-based meta-analysis, we uncovered 13 genome-wide significant regions that host single nucleotide polymorphisms with a high posterior probability for association with all three studied disorders (m-value > 0.9), 11 of which were not identified in previous cross-disorder analysis. In contrast, we also identified two additional pleiotropic regions in the TS-OCD meta-analysis. Through conditional analysis, we highlighted genes and genetic regions that play a specific role in a TS-ADHD-ASD genetic factor versus TS-OCD. Cross-disorder tissue specificity analysis implicated the hypothalamus-pituitary-adrenal gland axis in TS-ADHD-ASD.
Our work underlines the value of redefining the framework for research across traditional diagnostic categories.
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