Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS) in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn’s disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

The emergence of super-resolution (SR) fluorescence microscopy has rejuvenated the search for new cellular substructures. However, SR fluorescence microscopy achieves high contrast at the expense of a holistic view of the interacting partners and surrounding environment. Thus, we developed SR fluorescence-assisted diffraction computational tomography (SR-FACT), which combines label-free three-dimensional optical diffraction tomography (ODT) with two-dimensional fluorescence Hessian structured illumination microscopy. The ODT module is capable of resolving the mitochondria, lipid droplets, the nuclear membrane, chromosomes, the tubular endoplasmic reticulum, and lysosomes. Using dual-mode correlated live-cell imaging for a prolonged period of time, we observed novel subcellular structures named dark-vacuole bodies, the majority of which originate from densely populated perinuclear regions, and intensively interact with organelles such as the mitochondria and the nuclear membrane before ultimately collapsing into the plasma membrane. This work demonstrates the unique capabilities of SR-FACT, which suggests its wide applicability in cell biology in general.

Ellipse and hyperbola are two well-known curves in mathematics with numerous applications in various fields, but their properties and inherent differences in spin optics are less understood. Here, we investigate the peculiar optical spin properties of the two curves and establish a connection between their foci and the spin states of incident light. We show that the optical spin Hall effect is the intrinsic optical spin property of ellipse, where photons with different spin states can be exactly separated to each of its two foci. While a hyperbola exhibits optical spin-selective effect, where only photons with one particular spin state can be accumulated at its foci. These properties are then experimentally demonstrated in near field by arranging nanoslits in conic shape. Based on the spin properties of the curves, we design spin-based plasmonic devices with various functionalities. Our results reveal the intrinsic optical spin properties behind conic curves and provide a route for designing spin-based plasmonic device.

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Using a nondegenerate four-wave mixing process based on a double-Λ scheme in hot cesium vapor, we generate quantum correlated twin beams with a maximum intensity-difference squeezing of 6.5 dB. The substantially improved squeezing can be mainly attributed to very good frequency and phase-difference stability between the pump and probe beams in our experiment. Intensitydifference squeezing can be observed within a wide experimental parameter range, which guarantees its robust generation. Since this scheme produces multi-spatial-mode twin beams at the Cs D1 line, it is of interest for experiments involving quantum imaging and coherent interfaces between atomic and solid-state systems.

Using a nondegenerate four-wave mixing (FWM) process based on a double-Λ scheme in hot cesium vapor, we demonstrate a compact diode-laser-pumped quantum light source for the generation of quantum correlated twin beams with a maximum squeezing of 6.5 dB. The squeezing is observed at a Fourier frequency in the audio band down to 0.7 kHz which, to the best of our knowledge, is the first observation of sub-kilohertz intensity-difference squeezing in an atomic system so far. A phase-matching condition is also investigated in our system, which confirms the spatial-multi-mode characteristics of the FWM process. Our compact low-frequency squeezed light source may find applications in quantum imaging, quantum metrology, and the transfer of optical squeezing onto a matter wave.

Selective cleavage of C–C bonds within arene rings is of great interest but remains elusive, especially for the molecules possessing the active and inert C–C bonds. Here, we report that the active and inert C–C bonds of biphenylene could be controllably cleaved by the reaction of biphenylene, potassium graphite, and rare-earth complexes with different metal centers. For scandium, the bond activation occurs at the Caryl–Caryl single bond, yielding 9-scandafluorene. For Lu, the reaction goes through ring contraction of the aromatic ring in biphenylene to provide benzopentalene dianionic lutetium. The origin of the selectivity and the reaction mechanism were illustrated by the isolation of intermediates and DFT calculations.

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