Superlattices have attracted great interest because their use may make it possible to modify the spectra of two-dimensional electron systems and, ultimately, create materials with tailored electronic ...properties. In previous studies (see, for example, refs 1-8), it proved difficult to realize superlattices with short periodicities and weak disorder, and most of their observed features could be explained in terms of cyclotron orbits commensurate with the superlattice. Evidence for the formation of superlattice minibands (forming a fractal spectrum known as Hofstadter's butterfly) has been limited to the observation of new low-field oscillations and an internal structure within Landau levels. Here we report transport properties of graphene placed on a boron nitride substrate and accurately aligned along its crystallographic directions. The substrate's moiré potential acts as a superlattice and leads to profound changes in the graphene's electronic spectrum. Second-generation Dirac points appear as pronounced peaks in resistivity, accompanied by reversal of the Hall effect. The latter indicates that the effective sign of the charge carriers changes within graphene's conduction and valence bands. Strong magnetic fields lead to Zak-type cloning of the third generation of Dirac points, which are observed as numerous neutrality points in fields where a unit fraction of the flux quantum pierces the superlattice unit cell. Graphene superlattices such as this one provide a way of studying the rich physics expected in incommensurable quantum systems and illustrate the possibility of controllably modifying the electronic spectra of two-dimensional atomic crystals by varying their crystallographic alignment within van der Waals heterostuctures.
We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data ...with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.
Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce relativistic jets with lifetimes of at least one million years, and the observation of ...the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found, potentially representing such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z ≈ 6.
In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced ...distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.
Background Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent ...studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear. Methods Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed. Results Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio HR: 1.14; 95% confidence interval CI: 1.11–1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12–1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07–1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07–1.18). Furthermore, the RDW–mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21–1.44). Conclusions RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.
3D-printing of conductive carbon materials in sensing applications and energy storage devices has significant potential, however high resistivity of 3D-printed filaments poses a challenge. Strategies ...to enhance sensors post printing are time consuming and can reduce structural integrity. In this work, we investigated the effects different printing layer thickness and orientation can have on the electron transfer kinetics and resistivity of conductive materials. The response of these electrodes was investigated by cyclic voltammetry, electrochemical impedance spectroscopy and imaging. Electrodes printed with the lowest layer thickness of 0.1 mm in a vertical orientation had the greatest conductivity. With increasing print layer thickness and printing in a horizontal orientation, the electrode was more resistive. This work is the first to demonstrate the significant impact 3D-printing parameters can have on the electron transfer kinetics of carbon conductive electrodes. The implications of this study are important in defining the manufacturing process of electrodes for all applications.
Electron transfer in 3D-printed electrodes: 3d-printed electrodes are printed in vertical and horizontal orientation with thickness ranging from 0.1 to 0.4 mm. Electron transfer kinetics are enhanced in vertical orientation at lower print layer thickness due to the formation of less air voids and more conductive pathways. Display omitted
The ability to manipulate and measure the time-frequency structure of quantum light is useful for information processing and metrology. Measuring this structure is also important when developing ...quantum light sources with high modal purity that can interfere with other independent sources. Here, we present and experimentally demonstrate a scheme based on intensity interferometry to measure the joint spectral mode of photon pairs produced by spontaneous parametric down-conversion. We observe correlations in the spectral phase of the photons due to chirp in the pump. We show that our scheme can be combined with stimulated emission tomography to quickly measure their mode using bright classical light. Our scheme does not require phase stability, nonlinearities, or spectral shaping and thus is an experimentally simple way of measuring the modal structure of quantum light.
Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show ...severe anxiety. The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood-brain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1β), IL-6, 1 L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGFβ induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.
Highlights • Ictal-interictal continuum abnormalities (IICAs) are common after subarachnoid hemorrhage (SAH). • IICAs are associated with higher risk for delayed cerebral ischemia (DCI), especially ...if they emerge late in the acute period after SAH. • Quantification of IICA features may assist in the development of an algorithm to predict DCI risk.
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