scKINETICS: inference of regulatory velocity with single-cell transcriptomics data.

MOTIVATION: Transcriptional dynamics are governed by the action of regulatory proteins and are fundamental to systems ranging from normal development to disease. RNA velocity methods for tracking phenotypic dynamics ignore information on the regulatory drivers of gene expression variability through time. RESULTS: We introduce scKINETICS (Key regulatory Interaction NETwork for Inferring Cell Speed), a dynamical model of gene expression change which is fit with the simultaneous learning of per-cell transcriptional velocities and a governing gene regulatory network. Fitting is accomplished through an expectation-maximization approach designed to learn the impact of each regulator on its target genes, leveraging biologically motivated priors from epigenetic data, gene-gene coexpression, and constraints on cells' future states imposed by the phenotypic manifold. Applying this approach to an acute pancreatitis dataset recapitulates a well-studied axis of acinar-to-ductal transdifferentiation whilst proposing novel regulators of this process, including factors with previously appreciated roles in driving pancreatic tumorigenesis. In benchmarking experiments, we show that scKINETICS successfully extends and improves existing velocity approaches to generate interpretable, mechanistic models of gene regulatory dynamics. AVAILABILITY AND IMPLEMENTATION: All python code and an accompanying Jupyter notebook with demonstrations are available at http://github.com/dpeerlab/scKINETICS.

Compact nanosecond Yb:YAG/V:YAG solid-state laser generating switchable radially and azimuthally beams.

We demonstrated a compact self-starting nanosecond Yb:YAG/V:YAG solid-state laser with cylindrical vector beams output modulated by the intracavity mode converter S-waveplate experimentally. We can deliver the stable Q-switched pulse with the highest repetition rate 3.61 kHz and minimum pulse width 26 ns at the wavelength of 1030.07 nm with the help of the V:YAG crystal. In addition, the switchable radially and azimuthally polarized beams can be realized with polarization extinction ratios of 92.3% and 89.6%, respectively. The compact laser configuration can provide solutions for generating stable nanosecond structured light, and may benefit the applications like micro/nano material processing.

1.7†µm sub-200 fs vortex beams generation from a thulium-doped all-fiber laser.

The pulsed 1.7 µm vortex beams (VBs) has significant research prospects in the fields of imaging and material processing. We experimentally demonstrate the generation of sub-200 fs pulsed VBs at 1.7 µm based on a home-made mode-selective coupler (MSC). Through dispersion management technology in a thulium-doped fiber laser, the stable linearly polarized VBs pulse directly emitting from the cavity is measured to be 186 fs with central wavelength of 1721.2 nm. By controlling the linear superposition of LP11 modes, cylindrical vector beams (CVBs) can also be obtained. In addition, a variety of bound states pulsed VBs at 1.7 µm can also be observed. Our finding provides an effective way to generate ultrashort pulsed VBs and CVBs at 1.7 µm waveband.

Dispersion of the third-order optical nonlinearities in 2D (PEA)2PbI4 perovskite film.

We report the wavelength-dependent third-order optical nonlinearity of two-dimensional halide organic-inorganic perovskite (PEA)2PbI4 film experimentally. The high-quality two-dimensional (PEA)2PbI4 film prepared via confinement-assisted drop-casting process exhibits ultrafast optical response and large third-order optical nonlinearities, and the measured nonlinear refractive index is closer to the quantum perturbation model accounting for the excitonic effect. In addition, the wavelength-dependent optical response transition from self-focusing to self-defocusing, saturable absorption to reverse saturable absorption has been observed and investigated. The experimental results confirm the large third-order optical nonlinearities in (PEA)2PbI4 film and may make inroads toward developing cost-effective high-performance optoelectronic devices.

High-damage-threshold mid-infrared saturable absorber enabled by tantalum carbide nanoparticles.

A stable mid-infrared saturable absorber with a high damage threshold is urgently required for high-performance optical modulation in the mid-infrared regime. Here, we demonstrate stable mid-infrared erbium-doped fiber laser generation modulated by tantalum carbide nanoparticles (TaC NPs) experimentally. The TaC NPs show high physicochemical stability, obvious nonlinear optical absorption, and a high damage threshold. By introducing the TaC-based saturable absorber into an erbium-doped fiber laser, stable nanosecond pulses can be successfully delivered with a minimum pulse duration of 575 ns and signal-to-noise ratio of over 40 dB. The experimental results show that TaC NPs can act as a stable mid-infrared pulse modulator, and may make inroads for developing highly stable broadband optoelectronic devices.

Highly stable soliton and bound soliton generation from a fiber laser mode-locked by VSe2 nanosheets.

We demonstrate the highly stable soliton generation from a fiber laser mode-locked by the VSe2 nanosheets experimentally. The VSe2 nanosheets prepared via the liquid phase exfoliation method exhibit ultrafast relaxation time and excellent nonlinear optical behavior with saturation intensity and modulation depth of 14.28 MW/cm2 and 19.11%, respectively. A highly stable mode-locked Er3+-doped fiber laser with pulse duration of 714 fs and signal-to-noise ratio of 78.44 dB has been delivered successfully based on the VSe2 nanosheets saturable absorber. In addition, the transition from the conventional soliton to bound-state soliton has been observed experimentally. Our results reveal that VSe2 nanosheets possess excellent nonlinear optical performance and can act as a robust optical platform for versatile optical applications.

Broadband saturable absorption of indium tin oxide nanocrystals toward mid-infrared regime.

We experimentally demonstrate the ultrabroadband optical nonlinearity of indium tin oxide nanocrystals (ITO NCs) in the mid-infrared regime. Especially, the ITO NCs show considerable saturation absorption behavior with large modulation depth covering the spectral range from 2-µm to 10-µm wavelength. We also demonstrate the application of the optical nonlinearity to successfully modulate the erbium-doped fluoride fiber laser to deliver a nanosecond pulse with a signal-to-noise ratio over 43 dB at 2.8-µm wavelength. The results provide a promising platform for the development of ITO-based broadband and robust optoelectronic devices toward the deep mid-infrared spectral range.

High energy switchable pulsed High-order Mode beams in a mode-locking Raman all-fiber laser with high efficiency.

High energy pulsed High-order Mode (HOM) beams has great potential in materials processing and particle acceleration. We experimentally demonstrate a high energy mode-locking Raman all-fiber laser with switchable HOM state. A home-made fiber mode-selective coupler (MSC) is used as the mode converter with a wide bandwidth of 60 nm. By combining advantages of MSC and stimulated Raman scattering, 1.1 µJ pulsed HOM beams directly emitting from the all-fiber cavity can be achieved. After controlling the category and phase delay of vector modal superposition, different pulsed HOM beams including cylindrical vector beams (CVBs) (radial and angular) and optical vortex beams (OVBs) are reasonably obtained with high purity (all over 95%), as well as arbitrary switching. Furtherly, the slope efficiency of HOM beams in the mode-locking and continuous wave operations are as much as 20.3% and 31.8%, respectively. It may provide an effective way to achieve high energy pulsed HOM beams.

Watt-level superfluorescent fiber source near 3 µm.

We report a watt-level mid-infrared (mid-IR) superfluorescent fiber source from ${{\rm Er}^{3 +}}$-doped ZBLAN fiber near 3 µm spectral range. With the power amplifier configuration, the mid-IR superfluorescent fiber source with power up to 1.85 W has been delivered successfully with slope efficiency about 18.6%. The experimental results may pave an avenue toward a high-power, high-temporal-stability superfluorescent source for versatile mid-IR applications.

Correlation between geometric parametric instability sidebands in graded-index multimode fibers.

The spectral analysis of the light propagating in normally dispersive graded-index multimode fibers is performed under initial noisy conditions. Based on the obtained spectra with multiple simulations in the presence of noise, we investigate the correlation in energy between the well-separated spectral sidebands through both the scattergrams and the frequency-dependent energy correlation map and find that conjugate couples are highly correlated while cross-combinations exhibit a very poor degree of correlation. These results reveal that the geometric parametric instability processes associated with each sideband pair occur independently from each other, which can provide significant insights into the fundamental dynamical effect of the geometric parametric instability and facilitate the future implementation of high-efficiency photon pair sources with reduced Raman decorrelations.

Thermally switchable bifunctional plasmonic metasurface for perfect absorption and polarization conversion based on VO2.

Perfect absorption and polarization conversion of electromagnetic wave (EM) are of significant importance for numerous optical applications. Vanadium dioxide (VO2), which can be converted from insulating state to metallic state by being exposed to different temperatures, is introduced into a metallic square loop to constitute a switchable bifunctional plasmonic metasurface for perfect absorption and polarization conversion. Combined theoretical analyses and numerical simulations, the results show that at temperature T = 356 K, the metasurface acts as a perfect absorber with nearly 91% absorptance at the wavelength of 1547 nm. When the temperature decreases to T = 292 K, the metasurface expresses as a high efficiency (about 94%) polarization converter with the polarization conversion ratio up to 86% around 1550 nm. The designed bifunctional metasurface has plenty of potential applications such as energy harvesting, optical sensing and imaging. Moreover, it can also provide guidance to research tunable, smart and multifunctional devices.

Sub-hundred nanosecond pulse generation from a black phosphorus Q-switched Er-doped fiber laser.

Black phosphorus (BP), a prosperous two-dimensional optoelectronic material, has been deeply developed for various optoelectronics applications. Here, we demonstrate a sub-hundred nanosecond passively Q-switched Er-doped all-fiber laser with BP as the saturable absorber (SA). The BP-SA is fabricated by a controllable optical deposition technique. To achieve the sub-hundred nanosecond Q-switching output, we deliberately enlarge the modulation depth of the BP-SA by suitably increasing the time and laser power of the optical deposition and shortening the laser cavity length with an integrated multifunctional component. A stable Q-switched pulse train was obtained with a pulse duration as narrow as 91 ns, and the Q-switched lasing characteristics based on the BP-SA have also been investigated and discussed. The experimental results indicate that the BP material can be employed as an effective SA for the nanosecond pulse generation.

Graded-index breathing solitons from Airy pulses in multimode fibers.

Breathing solitons, as localized wave packets with a periodic evolution in amplitude and duration, are able to model extreme wave events in complex nonlinear dispersive systems. We have numerically studied the formation and manipulation of graded-index breathing solitons embedded in nonlinear multimode fibers based on a single nonlinear Schrödinger equation that includes the spatial self-imaging effect through a periodically varying nonlinear parameter. Through changing specific parameters of the input optical field, we can manipulate the period and depth of graded-index breathing soliton dynamics under different relative strengths between the dispersion length and the self-imaging period of the multimode fiber. Our study can explicitly derive a robust mechanism to control the behavior of the breathing localized structure directly and contribute to a better understanding of the much more complex nonlinear graded-index soliton dynamics in multimode fibers.

Emission of multiple resonant radiations by spatiotemporal oscillation of multimode dark pulses.

In this paper, we illustrate how the periodically modulated nonlinear parameter induced by the spatial beam oscillation can be used to generate broadband resonant radiations, through a train of dark pulses in normally dispersive graded-index multimode fibers under the efficient quasi-phase-matching schemes. More precisely, we demonstrate that two co-propagating waves with equal intensities and certain temporal delays can induce the formation of a train of dark solitons, with each emitting multiple resonant radiation lines, which can possibly form multiple radiation continuums based on vast amount of excited dark solitons. The nonlinear-interaction-aided excitation of dark pulses and their radiations appear to occur through a deterministic pathway, in sharp contrast to the situation for bright pulses in the anomalous dispersion region. The quasi-phase-matching condition via periodic oscillation of spatial beam in the normal-dispersion regime adds a unique dimension to the physical design of multimode waveguides, allowing the spectrum to be engineered for specific applications.

Bulk-structured PtSe2 for femtosecond fiber laser mode-locking.

The interest in pulsed fiber laser technology surrounds lots of critical optoelectronic applications ranging from optical communications, remote sensing to industrial material processing. Here, a femtosecond Er-doped fiber laser at 1560 nm have been demonstrated by using bulk-structured transition metal dichalcogenides (TMDs) - PtSe2 as the pulse modulator. The PtSe2 modulator was fabricated by using mechanically exfoliated methods from its single crystal and the exfoliated PtSe2 was directly transferred to the polished surface of the D-shaped fiber. Due to the strong interaction between PtSe2 and evanescent field, a self-starting Q-switched operation can be obtained. Furthermore, the mode-locking operation can be achieved easily by controlling the intra-cavity polarization states. Stable mode-locked operation can be maintained with pulse duration of 861 fs and signal to noise ratio (SNR) of 61.1 dB. These experimental results can validate the excellent nonlinear optical performance of PtSe2, and may make inroads for the ultrafast applications of the bulk and low-dimensional TMDs.

Peyer's patches-derived CD11b+ B cells recruit regulatory T cells through CXCL9 in dextran sulphate sodium-induced colitis.

Regulatory T (Treg) cells play an essential role in the maintenance of intestinal homeostasis. In Peyer's patches (PPs), which comprise the most important IgA induction site in the gut-associated lymphoid tissue, Treg cells promote IgA isotype switching. However, the mechanisms underlying their entry into PPs and isotype switching facilitation in activated B cells remain unknown. This study, based on the dextran sulphate sodium (DSS)-induced colitis model, revealed that Treg cells are significantly increased in PPs, along with CD11b+ B-cell induction. Immunofluorescence staining showed that infiltrated Treg cells were located around CD11b+ B cells and produced transforming growth factor-ß, thereby inducing IgA+ B cells. Furthermore, in vivo and in vitro studies revealed that CD11b+ B cells in PPs had the capacity to recruit Treg cells into PPs rather than promoting their proliferation. Finally, we found that Treg cell recruitment was mediated by the chemokine CXCL9 derived from CD11b+ B cells in PPs. These findings demonstrate that CD11b+ B cells induced in PPs during colitis actively recruit Treg cells to accomplish IgA isotype switch in a CXCL9-dependent manner.

The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy.

BACKGROUND: PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies. METHODS: The distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model. The expression of PD-L1 in immune cell populations was detected by flow cytometry. Data excavated from TCGA LGG/GBM datasets and the Ivy Glioblastoma Atlas Project was used for in silico analysis of the correlation among genes and survival. RESULTS: The distribution of tumor-infiltrating T cells and PD-L1 expression, which parallels in murine orthotopic glioma model and human glioma microdissections, was interrelated. The IFN-γ level was positively correlated with PD-L1 expression in murine glioma. Further, IFN-γ induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN-γ-induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN-γ level. By combining the relative expression of the listed IFN-γ-induced genes, IFN-γ score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies. CONCLUSION: Our study identified the distribution of tumor-infiltrating T cells and PD-L1 expression in murine glioma model and human glioma samples. And we found that IFN-γ is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN-γ score aggregated from the expressions of the listed IFN-γ-induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy.

Dark solitons manipulation using optical event horizon.

We demonstrate that the optical event horizon can provide an effective technique to actively control the propagation properties of a dark soliton with another weak probe wave. Careful power adjustment of the probe wave enables the black soliton converted into a gray one with varying grayness through the nonlinear interaction, corresponding to a nearly adiabatic variation of the soliton's speed. The sign of the phase angle for the newly formed gray soliton at optical event horizon is significantly dependent on the frequency of the launched probe wave. Linear-stability analysis of dark solitons under the perturbation of a weak probe wave is performed to clarify the intrinsic mechanism of the nonlinear interaction. The probe wave manipulated collisional dynamics between both dark solitons are investigated as an analogue of the combined white-hole and black-hole horizons which provides some insights into exploring the transition between integrable and non-integrable systems.

Dirac semimetals based tunable narrowband absorber at terahertz frequencies.

In this paper, a bulk Dirac semimetals (BDSs) based tunable narrowband absorber at terahertz frequencies is proposed and it has the attractive property of being polarization-independent at normal incidence because of its 90° rotational symmetry. Numerical results show that the absorption bandwidth is about 1.469e-2 THz and the total quality factor Q, defined as Q = f0/Δf, reaches about 94.6, which can be attributed to the low power loss of the guided mode resonance in the dielectric layer. The simulation results are analyzed with coupled mode theory. Interestingly, on the premise of maintaining the absorbance at a level greater than 0.95, the absorption frequency can be tuned from 1.381 to 1.395 THz by varying the Fermi energy of BDSs from 50 to 80 meV. Our results may also provide potential applications in optical filter and bio-chemical sensing.

Optical event horizon-based complete transformation and control of dark solitons.

We propose a manipulation approach to vary the wave speed, as well as the grayness, of dark solitons under the optical event horizon arising from the interaction between a dark soliton and a probe wave. To the best of our knowledge, the optical event horizon effect is demonstrated for the first time to be capable of inducing a reversible conversion between a black soliton and a gray one. This reversible soliton transformation and control process originates from the intrinsic competition between the probe-induced nonlinear phase shift and the internal phase of the dark soliton. In a cascaded system consisting of two optical event horizons, we also observe the new optical soliton tunneling phenomena where a dark soliton can be reset longitudinally purposely. The results may find applications in information cloaking such as effectively hiding the presence of intermediate fiber section to the receiver.