FreePSI: an alignment-free approach to estimating exon-inclusion ratios without a reference transcriptome.

Alternative splicing plays an important role in many cellular processes of eukaryotic organisms. The exon-inclusion ratio, also known as percent spliced in, is often regarded as one of the most effective measures of alternative splicing events. The existing methods for estimating exon-inclusion ratios at the genome scale all require the existence of a reference transcriptome. In this paper, we propose an alignment-free method, FreePSI, to perform genome-wide estimation of exon-inclusion ratios from RNA-Seq data without relying on the guidance of a reference transcriptome. It uses a novel probabilistic generative model based on k-mer profiles to quantify the exon-inclusion ratios at the genome scale and an efficient expectation-maximization algorithm based on a divide-and-conquer strategy and ultrafast conjugate gradient projection descent method to solve the model. We compare FreePSI with the existing methods on simulated and real RNA-seq data in terms of both accuracy and efficiency and show that it is able to achieve very good performance even though a reference transcriptome is not provided. Our results suggest that FreePSI may have important applications in performing alternative splicing analysis for organisms that do not have quality reference transcriptomes. FreePSI is implemented in C++ and freely available to the public on GitHub

Interaction-free, single-pixel quantum imaging with undetected photons

A typical imaging scenario requires three basic ingredients: 1. a light source that emits light, which in turn interacts and scatters off the object of interest; 2. detection of the light being scattered from the object and 3. a detector with spatial resolution. These indispensable ingredients in typical imaging scenarios may limit their applicability in the imaging of biological or other sensitive specimens due to unavailable photon-starved detection capabilities and inevitable damage induced by interaction. Here, we propose and experimentally realize a quantum imaging protocol that alleviates all three requirements. By embedding a single-photon Michelson interferometer into a nonlinear interferometer based on induced coherence and harnessing single-pixel imaging technique, we demonstrate interaction-free, single-pixel quantum imaging of a structured object with undetected photons. Thereby, we push the capability of quantum imaging to the extreme point in which no interaction is required between object and photons and the detection requirement is greatly reduced. Our work paves the path for applications in characterizing delicate samples with single-pixel imaging at silicon-detectable wavelengths

On-chip generation and collectively coherent control of the superposition of the whole family of Dicke states

Integrated quantum photonics has recently emerged as a powerful platform for generating, manipulating, and detecting entangled photons. Multipartite entangled states lie at the heart of the quantum physics and are the key enabling resources for scalable quantum information processing. Dicke state is an important class of genuinely entangled state, which has been systematically studied in the light-matter interactions, quantum state engineering and quantum metrology. Here, by using a silicon photonic chip, we report the generation and collectively coherent control of the entire family of four-photon Dicke states, i.e. with arbitrary excitations. We generate four entangled photons from two microresonators and coherently control them in a linear-optic quantum circuit, in which the nonlinear and linear processing are achieved in a chip-scale device. The generated photons are in telecom band, which lays the groundwork for large-scale photonic quantum technologies for multiparty networking and metrology.Comment: 19 pages, 4 figures in the main text and 13 figures in the Supplemental Materia

Polarization-entangled quantum frequency comb

Integrated micro-resonator facilitates the realization of quantum frequency comb (QFC), which provides a large number of discrete frequency modes with broadband spectral range and narrow linewidth. However, all previous demonstrations have focused on the generation of energy-time or time-bin entangled photons from QFC. Realizing polarization-entangled quantum frequency comb, which is the important resource for fundamental study of quantum mechanics and quantum information applications, remains challenging. Here, we demonstrate, for the first time, a broadband polarization-entangled quantum frequency comb by combining an integrated silicon nitride micro-resonator with a Sagnac interferometer. With a free spectral range of about 99 GHz and a narrow linewidth of about 190 MHz, our source provides 22 polarization entangled photons pairs with frequency covering the whole telecom C-band. The entanglement fidelities for all 22 pairs are above 81%, including 17 pairs with fidelities higher than 90%. Our demonstration paves the way for employing the polarization-entangled quantum frequency comb in quantum network using CMOS technology as well as standard dense wavelength division multiplexing technology.Comment: 11 pages, 9 figure

Quantum storage of entangled photons at telecom wavelengths in a crystal

The quantum internet -- in synergy with the internet that we use today -- promises an enabling platform for next-generation information processing, including exponentially speed-up distributed computation, secure communication, and high-precision metrology. The key ingredients for realizing such a global network are the distribution and storage of quantum entanglement. As quantum networks are likely to be based on existing fibre networks, telecom-wavelength entangled photons and corresponding quantum memories are of central interest. Recently, ${\rm ^{167}Er^{3+}}$ ions have been identified as a promising candidate for an efficient, broadband quantum memory at telecom wavelength. However, to date, no storage of entangled photons, the crucial step of quantum memory using these ions, has been reported. Here, we demonstrate the storage and recall of the entangled state of two telecom photons generated from an integrated photonic chip based on silicon nitride. Combining the natural narrow linewidth of the entangled photons and long storage time of ${\rm ^{167}Er^{3+}}$ ions, we achieve storage time of 400 ns, more than one order of magnitude longer than in previous works. Successful storage of entanglement in the crystal is certified by a violation of an entanglement witness by more than 12 standard deviations (-0.161 $\pm$ 0.012) at 400 ns storage time. These results pave the way for realizing quantum networks based on solid-state devices.Comment: 15 pages, 11 figure

Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and response in vivo

Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins