Tunable quantum emitters on large-scale foundry silicon photonics.

Controlling large-scale many-body quantum systems at the level of single photons and single atomic systems is a central goal in quantum information science and technology. Intensive research and development has propelled foundry-based silicon-on-insulator photonic integrated circuits to a leading platform for large-scale optical control with individual mode programmability. However, integrating atomic quantum systems with single-emitter tunability remains an open challenge. Here, we overcome this barrier through the hybrid integration of multiple InAs/InP microchiplets containing high-brightness infrared semiconductor quantum dot single photon emitters into advanced silicon-on-insulator photonic integrated circuits fabricated in a 300 mm foundry process. With this platform, we achieve single-photon emission via resonance fluorescence and scalable emission wavelength tunability. The combined control of photonic and quantum systems opens the door to programmable quantum information processors manufactured in leading semiconductor foundries.

A self-referenced interferometer for in situ cryogenic wafer curvature measurements.

A self-referenced interferometer to measure time-varying curvature in mechanically unstable environments is needed in many applications. One application that demands this measurement technique with fast data acquisition, 2D sensitivity, and insensitivity to vibration is the measurement of thermal strain in thin films in operational environments. The diverging beam interferometer described here demonstrates an angular sensitivity to the local curvature using interferograms captured by a CMOS camera. Two-dimensional Fourier analysis is used to extract curvature changes. The interferometer demonstrates an experimental sensitivity to curvature changes on the order of 10-4 m-1 and is used to measure thermal stresses in a cryogenic environment of a polycrystalline titanium nitride thin film on a silicon wafer that exhibits anisotropic curvature.

Bright Telecom-Wavelength Single Photons Based on a Tapered Nanobeam.

Telecom-wavelength single photons are essential components for long-distance quantum networks. However, bright and pure single photon sources at telecom wavelengths remain challenging to achieve. Here, we demonstrate a bright telecom-wavelength single photon source based on a tapered nanobeam containing InAs/InP quantum dots. The tapered nanobeam enables directional and Gaussian-like far-field emission of the quantum dots. As a result, using above-band excitation we obtain an end-to-end brightness of 4.1 ± 0.1% and first-lens brightness of 27.0 ± 0.1% at the ∼1300 nm wavelength. Furthermore, we adopt quasi-resonant excitation to reduce both multiphoton emission and decoherence from unwanted charge carriers. As a result, we achieve a coherence time of 523 ± 16 ps and postselected Hong-Ou-Mandel visibility of 0.91 ± 0.09 along with a comparable first-lens brightness of 21.0 ± 0.1%. These results represent a major step toward a practical fiber-based single photon source at telecom wavelengths for long-distance quantum networks.

Split-sample comparison of urothelial cells in ThinPrep and cytospin preparations in urinary cytology: Do we need to adjust The Paris System for Reporting Urinary Cytology criteria?

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) defines clear morphologic criteria to classify urinary specimens into 7 diagnostic categories. According to TPS, a nuclear-to-cytoplasmic ratio (N:C ratio) >0.7 and hyperchromasia must be observed to render a diagnosis of high-grade urothelial carcinoma (HGUC). TPS was established using only liquid-based preparation techniques, and to the authors' knowledge it is unknown whether TPS can be applied using other preparation methods. METHODS: In the current prospective study, voided urine samples from patients with HGUC and negative for HGUC (NHGUC) were prepared using both ThinPrep and cytospin methods. ImageJ image processing software was used to measure the N:C ratio and hyperchromasia. For each patient, the N:C ratio and degree of hyperchromasia of urothelial cells present in both cytopreparations were compared. RESULTS: A total of 10 HGUC cases and 9 NHGUC cases, represented by a total of 688 cells (mean, 36.7 cells in HGUC cases; and mean, 35.8 cells in NHGUC cases), were evaluated in the current study. An overall comparison of HGUC cells with NHGUC cells demonstrated that HGUC cells had a higher average N:C ratio (0.5465 vs 0.2846) and greater hyperchromasia as measured by the average nuclear pixel gray value (100.8 vs 120.7). The N:C ratio was statistically different in 4 NHGUC cases, demonstrating higher N:C ratios in the ThinPrep preparations. Hyperchromasia was found to be statistically different in 6 cases, 5 of which demonstrated increased hyperchromasia in the ThinPrep specimens. CONCLUSIONS: The morphologic features of HGUC cells appear to be similar in samples prepared using the ThinPrep and cytospin methods, and therefore TPS criteria may be applied successfully in laboratories that use these methods.

Super-Radiant Emission from Quantum Dots in a Nanophotonic Waveguide.

Future scalable photonic quantum information processing relies on the ability of integrating multiple interacting quantum emitters into a single chip. Quantum dots provide ideal on-chip quantum light sources. However, achieving quantum interaction between multiple quantum dots on-a-chip is a challenging task due to the randomness in their frequency and position, requiring local tuning technique and long-range quantum interaction. Here, we demonstrate quantum interactions between separated two quantum dots on a nanophotonic waveguide. We achieve a photon-mediated long-range interaction by integrating the quantum dots to the same optical mode of a nanophotonic waveguide and overcome spectral mismatch by incorporating on-chip thermal tuners. We observe their quantum interactions of the form of super-radiant emission, where the two dots collectively emit faster than each dot individually. Creating super-radiant emission from integrated quantum emitters could enable compact chip-integrated photonic structures that exhibit long-range quantum interactions. Therefore, these results represent a major step toward establishing photonic quantum information processors composed of multiple interacting quantum emitters on a semiconductor chip.

Perfect Strain Relaxation in Metamorphic Epitaxial Aluminum on Silicon through Primary and Secondary Interface Misfit Dislocation Arrays.

Understanding the atomically precise arrangement of atoms at epitaxial interfaces is important for emerging technologies such as quantum materials that have function and performance dictated by bonds and defects that are energetically active on the micro-electronvolt scale. A combination of atomistic modeling and dislocation theory analysis describes both primary and secondary dislocation networks at the metamorphic Al/Si (111) interface, which is experimentally validated by atomic resolution scanning transmission electron microscopy. The electron microscopy images show primary misfit dislocations for the majority of the strain relief and evidence of a secondary structure allowing for complete relaxation of the Al-Si misfit strain. This study demonstrates the equilibrium interface that represents the lowest energy structure of a highly mismatched and semicoherent single-crystal interface with complete strain relief in an atomically abrupt structure.

Patterns of co-occurring addictions, posttraumatic stress disorder, and major depressive disorder in detoxification treatment seekers: Implications for improving detoxification treatment outcomes.

BACKGROUND AND OBJECTIVES: Poly-substance use and psychiatric comorbidity are common among individuals receiving substance detoxification services. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most common co-occurring psychiatric disorders with substance use disorder (SUD). Current treatment favors a one-size-fits-all approach to treating addiction focusing on one substance or one comorbidity. Research examining patterns of substance use and comorbidities can inform efforts to effectively identify and differentially treat individuals with co-occurring conditions. METHODS: Using latent class analysis, the current study identified four patterns of PTSD, MDD, and substance use among 375 addiction treatment seekers receiving medically supervised detoxification. RESULTS: The four identified classes were: 1) a PTSD-MDD-Poly SUD class characterized by PTSD and MDD occurring in the context of opioid, cannabis, and tobacco use disorders; 2) an MDD-Poly SUD class characterized by MDD and alcohol, opioid, tobacco, and cannabis use disorders; 3) an alcohol-tobacco class characterized by alcohol and tobacco use disorders; and 4) an opioid-tobacco use disorder class characterized by opioid and tobacco use disorders. The observed classes differed on gender and clinical characteristics including addiction severity, trauma history, and PTSD/MDD symptom severity. DISCUSSION AND CONCLUSIONS: The observed classes likely require differing treatment approaches. For example, people in the PTSD-MDD-Poly SUD class would likely benefit from treatment approaches targeting anxiety sensitivity and distress tolerance, while the opioid-tobacco class would benefit from treatments that incorporate motivational interviewing. Appropriate matching of treatment to class could optimize treatment outcomes for polysubstance and comorbid psychiatric treatment seekers. These findings also underscore the importance of well-developed referral networks to optimize outpatient psychotherapy for detoxification treatment-seekers to enhance long-term recovery, particularly those that include transdiagnostic treatment components.

Hybrid Integration of Solid-State Quantum Emitters on a Silicon Photonic Chip.

Scalable quantum photonic systems require efficient single photon sources coupled to integrated photonic devices. Solid-state quantum emitters can generate single photons with high efficiency, while silicon photonic circuits can manipulate them in an integrated device structure. Combining these two material platforms could, therefore, significantly increase the complexity of integrated quantum photonic devices. Here, we demonstrate hybrid integration of solid-state quantum emitters to a silicon photonic device. We develop a pick-and-place technique that can position epitaxially grown InAs/InP quantum dots emitting at telecom wavelengths on a silicon photonic chip deterministically with nanoscale precision. We employ an adiabatic tapering approach to transfer the emission from the quantum dots to the waveguide with high efficiency. We also incorporate an on-chip silicon-photonic beamsplitter to perform a Hanbury-Brown and Twiss measurement. Our approach could enable integration of precharacterized III-V quantum photonic devices into large-scale photonic structures to enable complex devices composed of many emitters and photons.

Identification and analysis of mutational hotspots in oncogenes and tumour suppressors.

BACKGROUND: The key to interpreting the contribution of a disease-associated mutation in the development and progression of cancer is an understanding of the consequences of that mutation both on the function of the affected protein and on the pathways in which that protein is involved. Protein domains encapsulate function and position-specific domain based analysis of mutations have been shown to help elucidate their phenotypes. RESULTS: In this paper we examine the domain biases in oncogenes and tumour suppressors, and find that their domain compositions substantially differ. Using data from over 30 different cancers from whole-exome sequencing cancer genomic projects we mapped over one million mutations to their respective Pfam domains to identify which domains are enriched in any of three different classes of mutation; missense, indels or truncations. Next, we identified the mutational hotspots within domain families by mapping small mutations to equivalent positions in multiple sequence alignments of protein domainsWe find that gain of function mutations from oncogenes and loss of function mutations from tumour suppressors are normally found in different domain families and when observed in the same domain families, hotspot mutations are located at different positions within the multiple sequence alignment of the domain. CONCLUSIONS: By considering hotspots in tumour suppressors and oncogenes independently, we find that there are different specific positions within domain families that are particularly suited to accommodate either a loss or a gain of function mutation. The position is also dependent on the class of mutation.We find rare mutations co-located with well-known functional mutation hotspots, in members of homologous domain superfamilies, and we detect novel mutation hotspots in domain families previously unconnected with cancer. The results of this analysis can be accessed through the MOKCa database (http://strubiol.icr.ac.uk/extra/MOKCa).

Two-Photon Interference from the Far-Field Emission of Chip-Integrated Cavity-Coupled Emitters.

Interactions between solid-state quantum emitters and cavities are important for a broad range of applications in quantum communication, linear optical quantum computing, nonlinear photonics, and photonic quantum simulation. These applications often require combining many devices on a single chip with identical emission wavelengths in order to generate two-photon interference, the primary mechanism for achieving effective photon-photon interactions. Such integration remains extremely challenging due to inhomogeneous broadening and fabrication errors that randomize the resonant frequencies of both the emitters and cavities. In this Letter, we demonstrate two-photon interference from independent cavity-coupled emitters on the same chip, providing a potential solution to this long-standing problem. We overcome spectral mismatch between different cavities due to fabrication errors by depositing and locally evaporating a thin layer of condensed nitrogen. We integrate optical heaters to tune individual dots within each cavity to the same resonance with better than 3 µeV of precision. Combining these tuning methods, we demonstrate two-photon interference between two devices spaced by less than 15 µm on the same chip with a postselected visibility of 33%, which is limited by timing resolution of the detectors and background. These results pave the way to integrate multiple quantum light sources on the same chip to develop quantum photonic devices.

Mutational patterns in oncogenes and tumour suppressors.

All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved. In this paper we examine the mutation patterns observed in oncogenes and tumour suppressors, and discuss different approaches that have been developed to identify driver mutations within cancers that contribute to the disease progress. We also discuss the MOKCa database where we have developed an automatic pipeline that structurally and functionally annotates all proteins from the human proteome that are mutated in cancer.

Enhanced continuous-wave four-wave mixing efficiency in nonlinear AlGaAs waveguides.

Enhancements of the continuous-wave four-wave mixing conversion efficiency and bandwidth are accomplished through the application of plasma-assisted photoresist reflow to reduce the sidewall roughness of sub-square-micron-modal area waveguides. Nonlinear AlGaAs optical waveguides with a propagation loss of 0.56 dB/cm demonstrate continuous-wave four-wave mixing conversion efficiency of -7.8 dB. Narrow waveguides that are fabricated with engineered processing produce waveguides with uncoated sidewalls and anti-reflection coatings that show group velocity dispersion of +0.22 ps²/m. Waveguides that are 5-mm long demonstrate broadband four-wave mixing conversion efficiencies with a half-width 3-dB bandwidth of 63.8-nm.

Efficient continuous-wave four-wave mixing in bandgap-engineered AlGaAs waveguides.

We present a side-by-side comparison of the nonlinear behavior of four passive AlGaAs ridge waveguides where the bandgap energy of the core layers ranges from 1.60 to 1.79 eV. By engineering the bandgap to suppress two-photon absorption, minimizing the linear loss, and minimizing the mode area, we achieve efficient wavelength conversion in the C-band via partially degenerate four-wave mixing with a continuous-wave pump. The observed conversion efficiency [Idler(OUT)/Signal(IN)=-6.8 dB] is among the highest reported in passive semiconductor or glass waveguides.

Low propagation loss AlGaAs waveguides fabricated with plasma-assisted photoresist reflow.

We report low-loss deep-etch AlGaAs optical waveguides fabricated with nitrogen plasma-assisted photoresist reflow. The simultaneous application of a nitrogen plasma and heat is used to reduce the line edge roughness of patterned photoresist and limit the lateral spread of the photoresist patterns of submicron-scale waveguides. Comparison of the edge roughness of the etched sidewalls between the as-developed and smoothed photoresist etch samples show a reduction of the RMS roughness from 3.39±0.17 nm to 1.39±0.03 nm. The reduction in propagation loss is verified by measured waveguide loss as a function of waveguide widths. A 0.65-µm wide waveguide with a modal area of 0.4 µm(2) is fabricated with a propagation loss as low as 1.20±0.13 dB/cm for the transverse-electric mode.

Mid-infrared difference-frequency generation in suspended GaAs waveguides.

We experimentally demonstrate mid-infrared difference-frequency generation in suspended 181 nm thick GaAs waveguides. Generation of the idler at wavelengths between 2800 and 3150 nm is enabled by form-birefringent phase-matching in ultrahigh index-contrast waveguides. Nonlinear mixing has a measured efficiency of 0.4 W⁻¹ in a 1.2 mm long waveguide using a CW signal tunable between 1490 and 1620 nm and a CW pump tunable between 1018 and 1032 nm at powers of a few mW.

Examining the relationships between posttraumatic stress disorder symptoms, positive smoking outcome expectancies, and cigarette smoking in people with substance use disorders: a multiple mediator model.

Cigarette smoking is highly prevalent in people with substance use disorders (SUDs) and is associated with significant physical health problems. Posttraumatic stress disorder (PTSD) is also highly associated with both SUDs and cigarette smoking and may serve as a barrier to smoking cessation efforts. In addition, people with PTSD are more likely to hold positive smoking outcome expectancies (i.e., beliefs that smoking cigarettes results in positive outcomes); these beliefs may contribute to cigarette smoking in people with SUDs experiencing PTSD symptoms. The present study examined the relationship between PTSD symptoms and typical daily cigarette smoking/cigarette dependence symptoms in a sample of 227 trauma-exposed current smokers with SUDs (59.9% male, 89.4% Caucasian) seeking detoxification treatment services. Additionally, the indirect effects of multiple types of positive smoking outcome expectancies on these relationships were examined. Participants completed questionnaires assessing PTSD symptoms, positive smoking outcome expectancies, cigarette consumption, and cigarette dependence symptoms. Results indicated that PTSD symptoms were not directly related to cigarette consumption or cigarette dependence symptoms. However, negative affect reduction outcome expectancies were shown to have a significant indirect effect between PTSD symptoms and cigarette consumption, while negative affect reduction, boredom reduction, and taste-sensorimotor manipulation outcome expectancies were all found to have significant indirect effects between PTSD symptoms and cigarette dependence symptoms. The indirect effect involving negative affect reduction outcome expectancies was statistically larger than that of taste sensorimotor manipulation outcome expectancies, while negative affect reduction and boredom reduction outcome expectancies were comparable in magnitude. These results suggest that expectancies that smoking can manage negative affective experiences are related to cigarette smoking in people with SUDs experiencing PTSD symptoms and suggest that effective smoking cessation treatments should take into account these expectancies.

Measurement of small birefringence and loss in a nonlinear single-mode waveguide.

We design and fabricate a birefringent semiconductor waveguide for application to nonlinear photonics, demonstrating that it is possible to engineer a small birefringence into such a device using multiple core layers. We also demonstrate a simple technique to accurately determine small waveguide birefringence using a differential measurement, present useful methods for coupling light into and out of the device, and make estimates of coupling and linear device losses.

MoKCa database--mutations of kinases in cancer.

Members of the protein kinase family are amongst the most commonly mutated genes in human cancer, and both mutated and activated protein kinases have proved to be tractable targets for the development of new anticancer therapies The MoKCa database (Mutations of Kinases in Cancer, http://strubiol.icr.ac.uk/extra/mokca) has been developed to structurally and functionally annotate, and where possible predict, the phenotypic consequences of mutations in protein kinases implicated in cancer. Somatic mutation data from tumours and tumour cell lines have been mapped onto the crystal structures of the affected protein domains. Positions of the mutated amino-acids are highlighted on a sequence-based domain pictogram, as well as a 3D-image of the protein structure, and in a molecular graphics package, integrated for interactive viewing. The data associated with each mutation is presented in the Web interface, along with expert annotation of the detailed molecular functional implications of the mutation. Proteins are linked to functional annotation resources and are annotated with structural and functional features such as domains and phosphorylation sites. MoKCa aims to provide assessments available from multiple sources and algorithms for each potential cancer-associated mutation, and present these together in a consistent and coherent fashion to facilitate authoritative annotation by cancer biologists and structural biologists, directly involved in the generation and analysis of new mutational data.