The interplay between shell effects and electron correlations in quantum dots

We use the Path Integral Monte Carlo method to investigate the interplay between shell effects and electron correlations in single quantum dots with up to 12 electrons. By use of an energy estimator based on the hypervirial theorem of Hirschfelder we study the energy contributions of different interaction terms in detail. We discuss under which conditions the total spin of the electrons is given by Hund's rule, and the temperature dependence of the crystallization effects.Comment: 6 pages, 4 figure

High-purity microwave generation using a dual-frequency hybrid integrated semiconductor-dielectric waveguide laser

We present an integrated semiconductor-dielectric hybrid dual-frequency laser operating in the 1.5 $\mu$m wavelength range for microwave and terahertz (THz) generation. Generating a microwave beat frequency near 11 GHz, we observe a record-narrow intrinsic linewidth as low as about 2 kHz. This is realized by hybrid integration of a single diode amplifier based on indium phosphide (InP) with a long, low-loss silicon nitride (Si$_3$N$_4$) feedback circuit to extend the cavity photon lifetime, resulting in a cavity optical roundtrip length of about 30 cm on a chip. Simultaneous lasing at two frequencies is enabled by introducing an external control parameter for balancing the feedback from two tunable, frequency-selective Vernier mirrors on the Si$_3$N$_4$ chip. Each frequency can be tuned with a wavelength coverage of about 80 nm, potentially allowing for the generation of a broad range of frequencies in the microwave range up to the THz range

Ultra-narrow linewidth hybrid integrated semiconductor laser

We demonstrate a hybrid integrated and widely tunable diode laser with an intrinsic linewidth as narrow as 40 Hz, achieved with a single roundtrip through a low-loss feedback circuit that extends the cavity length to 0.5 meter on a chip. Employing solely dielectrics for single-roundtrip, single-mode resolved feedback filtering enables linewidth narrowing with increasing laser power, without limitations through nonlinear loss. We achieve single-frequency oscillation with up to 23 mW fiber coupled output power, 70-nm wide spectral coverage in the 1.55 $\mu$m wavelength range with 3 mW output, and obtain more than 60 dB side mode suppression. Such properties and options for further linewidth narrowing render the approach of high interest for direct integration in photonic circuits serving microwave photonics, coherent communications, sensing and metrology with highest resolution.Comment: 13 pages, and 11 figure

Takeaway meal consumption and risk markers for coronary heart disease, type 2 diabetes and obesity in children aged 9-10 years: a cross-sectional study.

OBJECTIVE: To investigate associations between takeaway meal consumption and risk markers for coronary heart disease, type 2 diabetes and obesity risk markers in children. DESIGN: A cross-sectional, school-based observational study. SETTING: 85 primary schools across London, Birmingham and Leicester. PARTICIPANTS: 1948 UK primary school children in year 5, aged 9-10 years. MAIN OUTCOME MEASURES: Children reported their frequency of takeaway meal consumption, completed a 24-hour dietary recall, had physical measurements and provided a fasting blood sample. RESULTS: Among 1948 participants with complete data, 499 (26%) never/hardly ever consumed a takeaway meal, 894 (46%) did so <1/week and 555 (28%) did ≥1/week. In models adjusted for age, sex, month, school, ethnicity and socioeconomic status, more frequent takeaway meal consumption was associated with higher dietary intakes of energy, fat % energy and saturated fat % energy and higher energy density (all P trend <0.001) and lower starch, protein and micronutrient intakes (all P trend <0.05). A higher frequency of takeaway meal consumption was associated with higher serum total cholesterol and low-density lipoprotein (LDL) cholesterol (P trend=0.04, 0.01, respectively); children eating a takeaway meal ≥1/week had total cholesterol and LDL cholesterol 0.09 mmol/L (95% CI 0.01 to 0.18) and 0.10 mmol/L (95% CI 0.02 to 0.18) higher respectively than children never/hardly ever eating a takeaway meal; their fat mass index was also higher. CONCLUSIONS: More frequent takeaway meal consumption in children was associated with unhealthy dietary nutrient intake patterns and potentially with adverse longer term consequences for obesity and coronary heart disease risk

Delineating the topography of amyloid-associated cortical atrophy in Down syndrome

Older adults with Down syndrome (DS) often have Alzheimer's disease (AD) neuropathologies. Although positron emission tomography imaging studies of amyloid deposition (beta amyloid, Aβ) have been associated with worse clinical prognosis and cognitive impairment, their relationships with cortical thickness remain unclear in people with DS. In a sample of 44 DS adults who underwent cognitive assessments, [C]-PiB positron emission tomography, and T1-weighted magnetization-prepared rapid gradient echo, we used mixed effect models to evaluate the spatial relationships between Aβ binding with patterns of cortical thickness. Partial Spearman correlations were used to delineate the topography of local Aβ-associated cortical thinning. [C]-PiB nondisplaceable binding potential was negatively associated with decreased cortical thickness. Locally, regional [C]-PiB retention was negatively correlated with cortical thickness in widespread cortices, predominantly in temporoparietal regions. Contrary to the prevailing evidence in established AD, we propose that our findings implicate Aβ in spatial patterns of atrophy that recapitulated the “cortical signature” of neurodegeneration in AD, conferring support to recent recommendations for earlier disease-interventions

MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes

Abstract Aims In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action. Methods and results We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. In the iPSC-CMs of the asymptomatic (AS) patient, the activity of an E3 ubiquitin-protein ligase (Nedd4L) involved in channel protein degradation was reduced and resulted in a decreased arrhythmogenic substrate. Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. Correction of these SNVs by CRISPR/Cas9 unmasked the LQTS phenotype in AS cells. Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. Thus, genetically mediated interference with Nedd4L activation seems associated with protective effects. Conclusion Our finding represents the first demonstration of the cellular mechanism of action of a protective modifier gene in LQTS. It provides new clues for advanced risk stratification and paves the way for the design of new therapies targeting this specific molecular pathway

Silicon Mie Resonators for Highly Directional Light Emission from monolayer MoS2

Controlling light emission from quantum emitters has important applications ranging from solid-state lighting and displays to nanoscale single-photon sources. Optical antennas have emerged as promising tools to achieve such control right at the location of the emitter, without the need for bulky, external optics. Semiconductor nanoantennas are particularly practical for this purpose because simple geometries, such as wires and spheres, support multiple, degenerate optical resonances. Here, we start by modifying Mie scattering theory developed for plane wave illumination to describe scattering of dipole emission. We then use this theory and experiments to demonstrate several pathways to achieve control over the directionality, polarization state, and spectral emission that rely on a coherent coupling of an emitting dipole to optical resonances of a Si nanowire. A forward-to-backward ratio of 20 was demonstrated for the electric dipole emission at 680 nm from a monolayer MoS2 by optically coupling it to a Si nanowire

Causas de Morte em Doentes com Hemofilia: Estudo Retrospectivo de 1979 a 2007, no Serviço de Imunohemoterapia do HSJ

Neurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because beta(2)-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the beta(2)-adrenoceptor agonist fenoterol on NK2 receptor messenger RNA (mRNA) and receptor density as well as the functional responses of bovine tracheal smooth muscle to the NK2 receptor agonist [beta-Ala(8)]-NKA(4-10) in vitro, using Northern blot analysis, receptor binding, and organ bath studies. Incubation with fenoterol induced a time- and concentration-dependent upregulation of NK2 receptor mRNA (71% increase after 12 h at 10(-7) M fenoterol), which was abolished by propranolol (a nonselective beta-adrenoceptor agonist) and ICI118551 (a selective beta(2)-adrenoceptor antagonist), but not by CGP20712A (a selective beta(1)-adrenoceptor antagonist), indicating that fenoterol acts via beta(2)-adrenoceptors. These effects were mimicked by forskolin and prostaglandin E-2 (PGE,), both agents that increase cyclic adenosine monophosphate (cAMP), and by the cAMP analogue 8-bromo-cAMP. The upregulation was blocked by cycloheximide, indicating that it requires new protein synthesis, and was accompanied by an increase in both the stability of NK2 receptor mRNA and the rate of NK2 receptor gene transcription. Radioligand binding assay using the selective NK2 receptor antagonist [H-3]SR48968 showed a significant increase in the number of receptor binding sites after 12 h and 18 h, which was accompanied by an increased contractile responsiveness to the NK2 receptor agonist [beta-Ala(8)]-NKA(4-10). Dexamethasone completely prevented the fenoterol-induced increase in NK2 receptor mRNA and in the contractile response. We conclude that beta(2)-adrenoceptor agonists induce upregulation of functional NK2 receptors in airway smooth muscle by increasing cAMP, and that this can be prevented by a corticosteroid. The increased responsiveness could be relevant to asthma control and mortality

Measuring agreement of administrative data with chart data using prevalence unadjusted and adjusted kappa

YesFunding provided by the Open Access Authors Fund