Fabrication of High‐Quality Thin Single‐Crystal Diamond Membranes with Low Surface Roughness

Certain aspects before and during the fabrication of single-crystal diamond (SCD) membranes are highlighted, which are decisive to obtain high-quality membranes with low surface roughness values around 0.2 nm on a small area scale. In addition to the requirements for the starting material, including a high planarity and a moderate surface roughness, the importance of cleaning processes to minimize particles and impurities before and during the structuring is emphasized. With the help of a planarization procedure, consisting of a combination of different Ar/Cl$_2$ recipes with low etch rates, surface defects like grooves due to polishing are minimized and smooth surfaces are acquired. Severe micromasking can be prevented by the application of a cyclic Ar/Cl$_2$ + O$_2$ recipe, allowing finally the fabrication of defect-minimized and planarized SCD membranes in the thickness range between few microns and a few hundred nanometers. The high quality of the structured SCD membranes is evidenced with a morphological as well as an optical characterization via fiber-based microcavity measurements

Scanning cavity microscopy of a single-crystal diamond membrane

Spin-bearing color centers in the solid state are promising candidates for the realization of quantum networks and distributed quantum computing. A remaining key challenge is their efficient and reliable interfacing to photons. Incorporating minimally processed membranes into open-access microcavities represents a promising route for Purcellenhanced spin-photon interfaces: it enables significant emission enhancement and efficient photon collection, minimizes deteriorating influence on the quantum emitter, and allows for full spatial and spectral tunability, key for controllably addressing suitable emitters with desired optical and spin properties. Here, we study the properties of a high-finesse fiber Fabry-Pérot microcavity with integrated single-crystal diamond membranes by scanning cavity microscopy. We observe spatially resolved the effects of the diamond-air interface on the cavity mode structure: a strong correlation of the cavity finesse and mode structure with the diamond thickness and surface topography, significant transverse-mode mixing under diamond-like conditions, and mode-character-dependent polarization-mode splitting. Our results reveal the influence of the diamond surface on the achievable Purcell enhancement, which helps to clarify the route towards optimized spin-photon interfaces

Scanning cavity microscopy of a single-crystal diamond membrane

Spin-bearing color centers in the solid state are promising candidates for the realization of quantum networks and distributed quantum computing. A remaining key challenge is their efficient and reliable interfacing to photons. Incorporating minimally processed membranes into open-access microcavities represents a promising route for Purcellenhanced spin-photon interfaces: it enables significant emission enhancement and efficient photon collection, minimizes deteriorating influence on the quantum emitter, and allows for full spatial and spectral tunability, key for controllably addressing suitable emitters with desired optical and spin properties. Here, we study the properties of a high-finesse fiber Fabry-P\'erot microcavity with integrated single-crystal diamond membranes by scanning cavity microscopy. We observe spatially resolved the effects of the diamond-air interface on the cavity mode structure: a strong correlation of the cavity finesse and mode structure with the diamond thickness and surface topography, significant transverse-mode mixing under diamond-like conditions, and mode-character-dependent polarization-mode splitting. Our results reveal the influence of the diamond surface on the achievable Purcell enhancement, which helps to clarify the route towards optimized spin-photon interfaces

Fabrication and Characterization of Single-Crystal Diamond Membranes for Quantum Photonics with Tunable Microcavities

The development of quantum technologies is one of the big challenges in modern research. Acrucial component for many applications is an efficient, coherent spin–photon interface, and coupling single-color centers in thin diamond membranes to a microcavity is a promising approach. To structure such micrometer thin single-crystal diamond (SCD) membranes with a good quality, it is important to minimize defects originating from polishing or etching procedures. Here, we report on the fabrication of SCD membranes, with various diameters, exhibiting a low surface roughness down to 0.4 nm on a small area scale, by etching through a diamond bulk mask with angled holes. A significant reduction in pits induced by micromasking and polishing damages was accomplished by the application of alternating Ar/Cl2 + O2 dry etching steps. By a variation of etching parameters regarding the Ar/Cl2 step, an enhanced planarization of the surface was obtained, in particular, for surfaces with a higher initial surface roughness of several nanometers. Furthermore, we present the successful bonding of an SCD membrane via van der Waals forces on a cavity mirror and perform finesse measurements which yielded values between 500 and 5000, depending on the position and hence on the membranethickness. Our results are promising for, e.g., an efficient spin–photon interface

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa