Accurate somatic variant detection using weakly supervised deep learning.

Identification of somatic mutations in tumor samples is commonly based on statistical methods in combination with heuristic filters. Here we develop VarNet, an end-to-end deep learning approach for identification of somatic variants from aligned tumor and matched normal DNA reads. VarNet is trained using image representations of 4.6 million high-confidence somatic variants annotated in 356 tumor whole genomes. We benchmark VarNet across a range of publicly available datasets, demonstrating performance often exceeding current state-of-the-art methods. Overall, our results demonstrate how a scalable deep learning approach could augment and potentially supplant human engineered features and heuristic filters in somatic variant calling.

Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism.SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential "hypo-priors" theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.

Structural and spectral dynamics of single-crystalline Ruddlesden-Popper phase halide perovskite blue light-emitting diodes.

Achieving perovskite-based high-color purity blue-emitting light-emitting diodes (LEDs) is still challenging. Here, we report successful synthesis of a series of blue-emissive two-dimensional Ruddlesden-Popper phase single crystals and their high-color purity blue-emitting LED demonstrations. Although this approach successfully achieves a series of bandgap emissions based on the different layer thicknesses, it still suffers from a conventional temperature-induced device degradation mechanism during high-voltage operations. To understand the underlying mechanism, we further elucidate temperature-induced device degradation by investigating the crystal structural and spectral evolution dynamics via in situ temperature-dependent single-crystal x-ray diffraction, photoluminescence (PL) characterization, and density functional theory calculation. The PL peak becomes asymmetrically broadened with a marked intensity decay, as temperature increases owing to [PbBr6]4- octahedra tilting and the organic chain disordering, which results in bandgap decrease. This study indicates that careful heat management under LED operation is a key factor to maintain the sharp and intense emission.

Self-Assembly of Two-Dimensional Perovskite Nanosheet Building Blocks into Ordered Ruddlesden-Popper Perovskite Phase.

The self-assembly of nanoparticles, a process whereby nanocrystal building blocks organize into even more ordered superstructures, is of great interest to nanoscience. Here we report the layer-by-layer assembly of 2D perovskite nanosheet building blocks. Structural analysis reveals that the assembled superlattice nanocrystals match with the layered Ruddlesden-Popper perovskite phase. This assembly proves reversible, as these superlattice nanocrystals can be reversibly exfoliated back into their building blocks via sonication. This study demonstrates the opportunity to further understand and exploit thermodynamics to increase order in a system of nanoparticles and to study emergent optical properties of a superlattice from 2D, weakly attracted, perovskite building blocks.

Quantitative imaging of anion exchange kinetics in halide perovskites.

Ion exchange, as a postsynthetic transformation strategy, offers more flexibilities in controlling material compositions and structures beyond direct synthetic methodology. Observation of such transformation kinetics on the single-particle level with rich spatial and spectroscopic information has never been achieved. We report the quantitative imaging of anion exchange kinetics in individual single-crystalline halide perovskite nanoplates using confocal photoluminescence microscopy. We have systematically observed a symmetrical anion exchange pathway on the nanoplates with dependence on reaction time and plate thickness, which is governed by the crystal structure and the diffusion-limited transformation mechanism. Based on a reaction-diffusion model, the halide diffusion coefficient was estimated to be on the order of [Formula: see text] This diffusion-controlled mechanism leads to the formation of 2D perovskite heterostructures with spatially resolved coherent interface through the precisely controlled anion exchange reaction, offering a design protocol for tailoring functionalities of semiconductors at the nano-/microscale.

Supervision contracts for mental health professionals: a systematic review and exploration of the potential relevance to psychiatry training in Australia and New Zealand.

OBJECTIVE: The use of formal supervision contracts has been strongly advocated across non-medical mental health professions. However, the use of such agreements is not a feature of the RANZCP Competency-Based Fellowship Program. This paper critically examines the evidence to support the use of formal supervision contracts. METHOD: A systematic review of empirical studies relating to the outcomes of supervision contracts was completed. Included records were subject to quality appraisal. RESULTS: Two studies met the inclusion criteria; both were assessed to be of poor quality. One study found improved supervision effectiveness associated with the use of supervision contracts, and the other found no significant differences associated with formal contracting. CONCLUSION: Despite strong advocacy, limited empirical evidence was found to support the value of formal supervision contracts across mental health professions. PROSPERO registration - PROSPERO 2018 CRD42018104142.

Intrinsic anion diffusivity in lead halide perovskites is facilitated by a soft lattice.

Facile ionic transport in lead halide perovskites plays a critical role in device performance. Understanding the microscopic origins of high ionic conductivities has been complicated by indirect measurements and sample microstructural heterogeneities. Here, we report the direct visualization of halide anion interdiffusion in CsPbCl3-CsPbBr3 single crystalline perovskite nanowire heterojunctions using wide-field and confocal photoluminescence measurements. The combination of nanoscale imaging techniques with these single crystalline materials allows us to measure intrinsic anionic lattice diffusivities, free from complications of microscale inhomogeneity. Halide diffusivities were found to be between 10-13 and ∼10-12 cm2/second at about 100 °C, which are several orders of magnitudes lower than those reported in polycrystalline thin films. Spatially resolved photoluminescence lifetimes and surface potential measurements provide evidence of the central role of halide vacancies in facilitating ionic diffusion. Vacancy formation free energies computed from molecular simulation are small due to the easily deformable perovskite lattice, accounting for the high equilibrium vacancy concentration. Furthermore, molecular simulations suggest that ionic motion is facilitated by low-frequency lattice modes, resulting in low activation barriers for vacancy-mediated transport. This work elucidates the intrinsic solid-state ion diffusion mechanisms in this class of semisoft materials and offers guidelines for engineering materials with long-term stability in functional devices.

Bacteria photosensitized by intracellular gold nanoclusters for solar fuel production.

The demand for renewable and sustainable fuel has prompted the rapid development of advanced nanotechnologies to effectively harness solar power. The construction of photosynthetic biohybrid systems (PBSs) aims to link preassembled biosynthetic pathways with inorganic light absorbers. This strategy inherits both the high light-harvesting efficiency of solid-state semiconductors and the superior catalytic performance of whole-cell microorganisms. Here, we introduce an intracellular, biocompatible light absorber, in the form of gold nanoclusters (AuNCs), to circumvent the sluggish kinetics of electron transfer for existing PBSs. Translocation of these AuNCs into non-photosynthetic bacteria enables photosynthesis of acetic acid from CO2. The AuNCs also serve as inhibitors of reactive oxygen species (ROS) to maintain high bacterium viability. With the dual advantages of light absorption and biocompatibility, this new generation of PBS can efficiently harvest sunlight and transfer photogenerated electrons to cellular metabolism, realizing CO2 fixation continuously over several days.

Giant Light-Emission Enhancement in Lead Halide Perovskites by Surface Oxygen Passivation.

Surface condition plays an important role in the optical performance of semiconductor materials. As new types of semiconductors, the emerging metal-halide perovskites are promising for next-generation optoelectronic devices. We discover significantly improved light-emission efficiencies in lead halide perovskites due to surface oxygen passivation. The enhancement manifests close to 3 orders of magnitude as the perovskite dimensions decrease to the nanoscale, improving external quantum efficiencies from <0.02% to over 12%. Along with about a 4-fold increase in spontaneous carrier recombination lifetimes, we show that oxygen exposure enhances light emission by reducing the nonradiative recombination channel. Supported by X-ray surface characterization and theoretical modeling, we propose that excess lead atoms on the perovskite surface create deep-level trap states that can be passivated by oxygen adsorption.

Electrical and Optical Tunability in All-Inorganic Halide Perovskite Alloy Nanowires.

Alloying different semiconductors is a powerful approach to tuning the optical and electronic properties of semiconductor materials. In halide perovskites (ABX3), alloys with different anions have been widely studied, and great band gap tunability in the visible range has been achieved. However, perovskite alloys with different cations at the "B" site are less understood due to the synthetic challenges. Herein, we first have developed the synthesis of single-crystalline CsPb xSn1- xI3 nanowires (NWs). The electronic band gaps of CsPb xSn1- xI3 NWs can be tuned from 1.3 to 1.78 eV by varying the Pb/Sn ratio, which leads to the tunable photoluminescence (PL) in the near-infrared range. More importantly, we found that the electrical conductivity increases as more Sn2+ is alloyed with Pb2+, possibly due to the increase of charge carrier concentration when more Sn2+ is introduced. The wide tunability of the optical and electronic properties makes CsPb xSn1- xI3 alloy NWs promising candidates for future optoelectronic device applications.

Nanostructuring Multilayer Hyperbolic Metamaterials for Ultrafast and Bright Green InGaN Quantum Wells.

Semiconductor quantum well (QW) light-emitting diodes (LEDs) have limited temporal modulation bandwidth of a few hundred MHz due to the long carrier recombination lifetime. Material doping and structure engineering typically leads to incremental change in the carrier recombination rate, whereas the plasmonic-based Purcell effect enables dramatic improvement for modulation frequency beyond the GHz limit. By stacking Ag-Si multilayers, the resulting hyperbolic metamaterials (HMMs) have shown tunability in the plasmonic density of states for enhancing light emission at various wavelengths. Here, nanopatterned Ag-Si multilayer HMMs are utilized for enhancing spontaneous carrier recombination rates in InGaN/GaN QWs. An enhancement of close to 160-fold is achieved in the spontaneous recombination rate across a broadband of working wavelengths accompanied by over tenfold enhancement in the QW peak emission intensity, thanks to the outcoupling of dominating HMM modes. The integration of nanopatterned HMMs with InGaN QWs will lead to ultrafast and bright QW LEDs with a 3 dB modulation bandwidth beyond 100 GHz for applications in high-speed optoelectronic devices, optical wireless communications, and light-fidelity networks.

Thermochromic halide perovskite solar cells.

Smart photovoltaic windows represent a promising green technology featuring tunable transparency and electrical power generation under external stimuli to control the light transmission and manage the solar energy. Here, we demonstrate a thermochromic solar cell for smart photovoltaic window applications utilizing the structural phase transitions in inorganic halide perovskite caesium lead iodide/bromide. The solar cells undergo thermally-driven, moisture-mediated reversible transitions between a transparent non-perovskite phase (81.7% visible transparency) with low power output and a deeply coloured perovskite phase (35.4% visible transparency) with high power output. The inorganic perovskites exhibit tunable colours and transparencies, a peak device efficiency above 7%, and a phase transition temperature as low as 105 °C. We demonstrate excellent device stability over repeated phase transition cycles without colour fade or performance degradation. The photovoltaic windows showing both photoactivity and thermochromic features represent key stepping-stones for integration with buildings, automobiles, information displays, and potentially many other technologies.

Highly stretchable, printable nanowire array optical polarizers.

Designing optical components such as polarizers on substrates with high mechanical deformability have potential to realize new device platforms in photonics, wearable electronics, and sensors. Conventional manufacturing approaches that rely highly on top-down lithography, deposition and the etching process can easily confront compatibility issues and high fabrication complexity. Therefore, an alternative integration scheme is necessary. Here, we demonstrate fabrication of highly flexible and stretchable wire grid polarizers (WGPs) by printing bottom-up grown Ge or Ge/Si core/shell nanowires (NWs) on device substrates in a highly dense and aligned fashion. The maximum contrast ratio of 104 between transverse electric (TE) and transverse magnetic (TM) fields and above 99% (maximum 99.7%) of light blocking efficiency across the visible spectrum range are achieved. Further systematic analyses are performed both in experimental and numerical models to reveal the correspondence between physical factors (coverage ratio of NW arrays and diameter) and polarization efficiency. Moreover, we demonstrate distinctive merits of our approach: (i) high flexibility in the choice of substrates such as glass, plastic, or elastomer; (ii) easy combination with additional novel functionalities, for example, air permeability, flexibility/stretchability, biocompatibility, and a skin-like low mechanical modulus; (iii) selective printing of polarizers on a designated local area.

Wide field super-resolution surface imaging through plasmonic structured illumination microscopy.

We experimentally demonstrate a wide field surface plasmon (SP) assisted super-resolution imaging technique, plasmonic structured illumination microscopy (PSIM), by combining tunable SP interference (SPI) with structured illumination microscopy (SIM). By replacing the laser interference fringes in conventional SIM with SPI patterns, PSIM exhibits greatly enhanced resolving power thanks to the unique properties of SP waves. This PSIM technique is a wide field, surface super-resolution imaging technique with potential applications in the field of high-speed biomedical imaging.

Ultralow thermal conductivity of multilayers with highly dissimilar Debye temperatures.

Thermal transport in multilayers (MLs) has attracted significant interest and shows promising applications. Unlike their single-component counterparts, MLs exhibit a thermal conductivity that can be effectively engineered by both the number density of the layers and the interfacial thermal resistance between layers, with the latter being highly tunable via the contrast of acoustic properties of each layer. In this work, we experimentally demonstrated an ultralow thermal conductivity of 0.33 ± 0.04 W m(-1) K(-1) at room temperature in MLs made of Au and Si with a high interfacial density of ∼0.2 interface nm(-1). The measured thermal conductivity is significantly lower than the amorphous limit of either Si or Au and is also much lower than previously measured MLs with a similar interfacial density. With a Debye temperature ratio of ∼3.9 for Au and Si, the Au/Si MLs represent the highest mismatched system in inorganic MLs measured to date. In addition, we explore the prior theoretical prediction that full phonon dispersion could better model the interfacial thermal resistance involving materials with low Debye temperatures. Our results demonstrate that MLs with highly dissimilar Debye temperatures represent a rational approach to achieve ultralow thermal conductivity in inorganic materials and can also serve as a platform for investigating interfacial thermal transport.

Enhanced spontaneous emission inside hyperbolic metamaterials.

Hyperbolic metamaterials can enhance spontaneous emission, but the radiation-matter coupling is not optimized if the light source is placed outside such media. We demonstrate a 3-fold improvement of the Purcell factor over its outer value and a significant enlargement in bandwidth by including the emitter within a Si/Ag periodic multilayer metamaterial. To extract the plasmonic modes of the structure into the far field we implement two types of 1D grating with triangular and rectangular profile, obtaining a 10-fold radiative enhancement at visible frequencies.

Enhancing spontaneous emission rates of molecules using nanopatterned multilayer hyperbolic metamaterials.

Plasmonic nanostructures have been extensively used to manipulate the spontaneous light emission rate of molecules and their radiative efficiency. Because molecules near a metallic surface experience a different environment than in free space, their spontaneous radiative emission rate is generally enhanced. Such enhancement, measured by means of the Purcell factor, arises as a consequence of the overlap between the surface plasmon mode frequency and the emission spectrum of the molecule. However, such overlap is available only for a few narrow bands of frequency due to the limited plasmonic materials existing in nature. Although this limitation can be overcome by using hyperbolic metamaterials (HMMs)­a type of nanoscale artificial material with hyperbolic dispersion relations­the Purcell factor and the radiative power have remained relatively low. Here, we show that by nanopatterning a hyperbolic metamaterial made of Ag and Si multilayers, the spontaneous emission rate of rhodamine dye molecules is enhanced 76-fold at tunable frequencies and the emission intensity of the dye increases by ~80-fold compared with the same hyperbolic metamaterial without nanostructuring. We explain these results using a dynamic Lorentzian model in the time domain.

Hyperlenses and metalenses for far-field super-resolution imaging.

The resolution of conventional optical lens systems is always hampered by the diffraction limit. Recent developments in artificial metamaterials provide new avenues to build hyperlenses and metalenses that are able to image beyond the diffraction limit. Hyperlenses project super-resolution information to the far field through a magnification mechanism, whereas metalenses not only super-resolve subwavelength details but also enable optical Fourier transforms. Recently, there have been numerous designs for hyperlenses and metalenses, bringing fresh theoretical and experimental advances, though future directions and challenges remain to be overcome.