Low Energy Electron Point Projection Microscopy of Suspended Graphene, the Ultimate "Microscope Slide"

Point Projection Microscopy (PPM) is used to image suspended graphene using low-energy electrons (100-200eV). Because of the low energies used, the graphene is neither damaged or contaminated by the electron beam. The transparency of graphene is measured to be 74%, equivalent to electron transmission through a sheet as thick as twice the covalent radius of sp^2-bonded carbon. Also observed is rippling in the structure of the suspended graphene, with a wavelength of approximately 26 nm. The interference of the electron beam due to the diffraction off the edge of a graphene knife edge is observed and used to calculate a virtual source size of 4.7 +/- 0.6 Angstroms for the electron emitter. It is demonstrated that graphene can be used as both anode and substrate in PPM in order to avoid distortions due to strong field gradients around nano-scale objects. Graphene can be used to image objects suspended on the sheet using PPM, and in the future, electron holography

Tunable Indistinguishable Photons From Remote Quantum Dots

Single semiconductor quantum dots have been widely studied within devices that can apply an electric field. In the most common system, the low energy offset between the InGaAs quantum dot and the surrounding GaAs material limits the magnitude of field that can be applied to tens of kVcm^-1, before carriers tunnel out of the dot. The Stark shift experienced by the emission line is typically 1 meV. We report that by embedding the quantum dots in a quantum well heterostructure the vertical field that can be applied is increased by over an order of magnitude whilst preserving the narrow linewidths, high internal quantum efficiencies and familiar emission spectra. Individual dots can then be continuously tuned to the same energy allowing for two-photon interference between remote, independent, quantum dots

Engineering of quantum dot photon sources via electro-elastic fields

The possibility to generate and manipulate non-classical light using the tools of mature semiconductor technology carries great promise for the implementation of quantum communication science. This is indeed one of the main driving forces behind ongoing research on the study of semiconductor quantum dots. Often referred to as artificial atoms, quantum dots can generate single and entangled photons on demand and, unlike their natural counterpart, can be easily integrated into well-established optoelectronic devices. However, the inherent random nature of the quantum dot growth processes results in a lack of control of their emission properties. This represents a major roadblock towards the exploitation of these quantum emitters in the foreseen applications. This chapter describes a novel class of quantum dot devices that uses the combined action of strain and electric fields to reshape the emission properties of single quantum dots. The resulting electro-elastic fields allow for control of emission and binding energies, charge states, and energy level splittings and are suitable to correct for the quantum dot structural asymmetries that usually prevent these semiconductor nanostructures from emitting polarization-entangled photons. Key experiments in this field are presented and future directions are discussed.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Mice expressing a human KATP channel mutation have altered channel ATP sensitivity but no cardiac abnormalities

AIMS/HYPOTHESIS: Patients with severe gain-of-function mutations in the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, have neonatal diabetes, muscle hypotonia and mental and motor developmental delay-a condition known as iDEND syndrome. However, despite the fact that Kir6.2 forms the pore of the cardiac K(ATP) channel, patients show no obvious cardiac symptoms. The aim of this project was to use a mouse model of iDEND syndrome to determine whether iDEND mutations affect cardiac function and cardiac K(ATP) channel ATP sensitivity. METHODS: We performed patch-clamp and in vivo cine-MRI studies on mice in which the most common iDEND mutation (Kir6.2-V59M) was targeted to cardiac muscle using Cre-lox technology (m-V59M mice). RESULTS: Patch-clamp studies of isolated cardiac myocytes revealed a markedly reduced K(ATP) channel sensitivity to MgATP inhibition in m-V59M mice (IC(50) 62 μmol/l compared with 13 μmol/l for littermate controls). In vivo cine-MRI revealed there were no gross morphological differences and no differences in heart rate, end diastolic volume, end systolic volume, stroke volume, ejection fraction, cardiac output or wall thickening between m-V59M and control hearts, either under resting conditions or under dobutamine stress. CONCLUSIONS/INTERPRETATION: The common iDEND mutation Kir6.2-V59M decreases ATP block of cardiac K(ATP) channels but was without obvious effect on heart function, suggesting that metabolic changes fail to open the mutated channel to an extent that affects function (at least in the absence of ischaemia). This may have implications for the choice of sulfonylurea used to treat neonatal diabetes

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Atmospheric Reconnaissance of TRAPPIST-1 b with JWST/NIRISS: Evidence for Strong Stellar Contamination in the Transmission Spectra

TRAPPIST-1 is a nearby system of seven Earth-sized, temperate, rocky exoplanets transiting a Jupiter-sized M8.5V star, ideally suited for in-depth atmospheric studies. Each TRAPPIST-1 planet has been observed in transmission both from space and from the ground, confidently rejecting cloud-free, hydrogen-rich atmospheres. Secondary eclipse observations of TRAPPIST-1 b with JWST/MIRI are consistent with little to no atmosphere given the lack of heat redistribution. Here we present the first transmission spectra of TRAPPIST-1 b obtained with JWST/NIRISS over two visits. The two transmission spectra show moderate to strong evidence of contamination from unocculted stellar heterogeneities, which dominates the signal in both visits. The transmission spectrum of the first visit is consistent with unocculted starspots and the second visit exhibits signatures of unocculted faculae. Fitting the stellar contamination and planetary atmosphere either sequentially or simultaneously, we confirm the absence of cloud-free hydrogen-rich atmospheres, but cannot assess the presence of secondary atmospheres. We find that the uncertainties associated with the lack of stellar model fidelity are one order of magnitude above the observation precision of 89 ppm (combining the two visits). Without affecting the conclusion regarding the atmosphere of TRAPPIST-1 b, this highlights an important caveat for future explorations, which calls for additional observations to characterize stellar heterogeneities empirically and/or theoretical works to improve model fidelity for such cool stars. This need is all the more justified as stellar contamination can affect the search for atmospheres around the outer, cooler TRAPPIST-1 planets for which transmission spectroscopy is currently the most efficient technique.Comment: 26 pages, 11 figures, accepted for publication in The Astrophysical Journal Letter

Quadrature squeezed photons from a two-level system.

Resonance fluorescence arises from the interaction of an optical field with a two-level system, and has played a fundamental role in the development of quantum optics and its applications. Despite its conceptual simplicity, it entails a wide range of intriguing phenomena, such as the Mollow-triplet emission spectrum, photon antibunching and coherent photon emission. One fundamental aspect of resonance fluorescence--squeezing in the form of reduced quantum fluctuations in the single photon stream from an atom in free space--was predicted more than 30 years ago. However, the requirement to operate in the weak excitation regime, together with the combination of modest oscillator strength of atoms and low collection efficiencies, has continued to necessitate stringent experimental conditions for the observation of squeezing with atoms. Attempts to circumvent these issues had to sacrifice antibunching, owing to either stimulated forward scattering from atomic ensembles or multi-photon transitions inside optical cavities. Here, we use an artificial atom with a large optical dipole enabling 100-fold improvement of the photon detection rate over the natural atom counterpart and reach the necessary conditions for the observation of quadrature squeezing in single resonance-fluorescence photons. By implementing phase-dependent homodyne intensity-correlation detection, we demonstrate that the electric field quadrature variance of resonance fluorescence is three per cent below the fundamental limit set by vacuum fluctuations, while the photon statistics remain antibunched. The presence of squeezing and antibunching simultaneously is a fully non-classical outcome of the wave-particle duality of photons.We acknowledge financial support from the University of Cambridge, the European Research Council ERC Consolidator Grant Agreement No. 617985 and the EU-FP7 Marie Curie Initial Training Network S3NANO. C.M. acknowledges Clare College Cambridge for financial support through a Junior Research Fellowship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1486

Voltage-Dependent Gating in a “Voltage Sensor-Less” Ion Channel

An unusual mechanism of ion channel regulation generates voltage-dependent gating in the absence of a canonical voltage-sensing domain

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H