Polarization states and far-field optical properties in dielectric photonic crystal slabs.

We study the role of topological singularities like Bound States in a Continuum (BICs) or Circularly Polarized States (CPSs) in determining ellipticity of the far-field polarization in dielectric metasurfaces. Using finite-difference time-domain as well as rigorous coupled-wave analysis simulations, we determine the behavior of the Stokes parameter S3 in the whole k space above the light cone, with special regard to the region close to the singularities. Moreover, we clarify the relation between the topological singularities and the circular dichroism in reflectivity.

Single SiGe quantum dot emission deterministically enhanced in a high-Q photonic crystal resonator.

We report the resonantly enhanced radiative emission from a single SiGe quantum dot (QD), which is deterministically embedded into a bichromatic photonic crystal resonator (PhCR) at the position of its largest modal electric field by a scalable method. By optimizing our molecular beam epitaxy (MBE) growth technique, we were able to reduce the amount of Ge within the whole resonator to obtain an absolute minimum of exactly one QD, accurately positioned by lithographic methods relative to the PhCR, and an otherwise flat, a few monolayer thin, Ge wetting layer (WL). With this method, record quality (Q) factors for QD-loaded PhCRs up to Q ∼ 105 are achieved. A comparison with control PhCRs on samples containing a WL but no QDs is presented, as well as a detailed analysis of the dependence of the resonator-coupled emission on temperature, excitation intensity, and emission decay after pulsed excitation. Our findings undoubtedly confirm a single QD in the center of the resonator as a potentially novel photon source in the telecom spectral range.

Strongly enhanced light-matter coupling of monolayer WS2 from a bound state in the continuum.

Exciton-polaritons derived from the strong light-matter interaction of an optical bound state in the continuum with an excitonic resonance can inherit an ultralong radiative lifetime and significant nonlinearities, but their realization in two-dimensional semiconductors remains challenging at room temperature. Here we show strong light-matter interaction enhancement and large exciton-polariton nonlinearities at room temperature by coupling monolayer tungsten disulfide excitons to a topologically protected bound state in the continuum moulded by a one-dimensional photonic crystal, and optimizing for the electric-field strength at the monolayer position through Bloch surface wave confinement. By a structured optimization approach, the coupling with the active material is maximized here in a fully open architecture, allowing to achieve a 100 meV photonic bandgap with the bound state in the continuum in a local energy minimum and a Rabi splitting of 70 meV, which results in very high cooperativity. Our architecture paves the way to a class of polariton devices based on topologically protected and highly interacting bound states in the continuum.

Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance.

Immunological protection of transplanted stem cell-derived islet (SC-islet) cells is yet to be achieved without chronic immunosuppression or encapsulation. Existing genetic engineering approaches to produce immune-evasive SC-islet cells have so far shown variable results. Here, we show that targeting human leukocyte antigens (HLAs) and PD-L1 alone does not sufficiently protect SC-islet cells from xenograft (xeno)- or allograft (allo)-rejection. As an addition to these approaches, we genetically engineer SC-islet cells to secrete the cytokines interleukin-10 (IL-10), transforming growth factor ß (TGF-ß), and modified IL-2 such that they promote a tolerogenic local microenvironment by recruiting regulatory T cells (Tregs) to the islet grafts. Cytokine-secreting human SC-ß cells resist xeno-rejection and correct diabetes for up to 8 weeks post-transplantation in non-obese diabetic (NOD) mice. Thus, genetically engineering human embryonic SCs (hESCs) to induce a tolerogenic local microenvironment represents a promising approach to provide SC-islet cells as a cell replacement therapy for diabetes without the requirement for encapsulation or immunosuppression.

Single-photon nonlinearities and blockade from a strongly driven photonic molecule.

Achieving the regime of single-photon nonlinearities in photonic devices by just exploiting the intrinsic high-order susceptibilities of conventional materials would open the door to practical semiconductor-based quantum photonic technologies. Here we show that this regime can be achieved in a triply resonant integrated photonic device made of two coupled ring resonators, in a material platform displaying an intrinsic third-order nonlinearity. By strongly driving one of the three resonances of the system, a weak coherent probe at one of the others results in a strongly suppressed two-photon probability at the output, evidenced by an antibunched second-order correlation function at zero-time delay under continuous wave driving.

Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets.

Human embryonic stem cells (hESCs) provide opportunities for cell replacement therapy of insulin-dependent diabetes. Therapeutic quantities of human stem cell-derived islets (SC-islets) can be produced by directed differentiation. However, preventing allo-rejection and recurring autoimmunity, without the use of encapsulation or systemic immunosuppressants, remains a challenge. An attractive approach is to transplant SC-islets, genetically modified to reduce the impact of immune rejection. To determine the underlying forces that drive immunogenicity of SC-islets in inflammatory environments, we performed single-cell RNA sequencing (scRNA-seq) and whole-genome CRISPR screen of SC-islets under immune interaction with allogeneic peripheral blood mononuclear cells (PBMCs). Data analysis points to "alarmed" populations of SC-islets that upregulate genes in the interferon (IFN) pathway. The CRISPR screen in vivo confirms that targeting IFNγ-induced mediators has beneficial effects on SC-islet survival under immune attack. Manipulating the IFN response by depleting chemokine ligand 10 (CXCL10) in SC-islet grafts confers improved survival against allo-rejection compared with wild-type grafts in humanized mice. These results offer insights into the nature of immune destruction of SC-islets during allogeneic responses and provide targets for gene editing.

Thermo-optically induced transparency on a photonic chip.

Controlling the optical response of a medium through suitably tuned coherent electromagnetic fields is highly relevant in a number of potential applications, from all-optical modulators to optical storage devices. In particular, electromagnetically induced transparency (EIT) is an established phenomenon in which destructive quantum interference creates a transparency window over a narrow spectral range around an absorption line, which, in turn, allows to slow and ultimately stop light due to the anomalous refractive index dispersion. Here we report on the observation of a new form of both induced transparency and amplification of a weak probe beam in a strongly driven silicon photonic crystal resonator at room temperature. The effect is based on the oscillating temperature field induced in a nonlinear optical cavity, and it reproduces many of the key features of EIT while being independent of either atomic or mechanical resonances. Such thermo-optically induced transparency will allow a versatile implementation of EIT-analogs in an integrated photonic platform, at almost arbitrary wavelength of interest, room temperature and in a practical, low cost, and scalable system.

A human ESC line for efficient CRISPR editing of pluripotent stem cells.

Human pluripotent stem cells (hPSC) can be directed to differentiate in vitro into insulin-prorducing beta cells (SC-ß). Although these cells accurately respond to glucose and can reverse diabetes in preclinical models improvments in the final cell products are desirable. For example, safety, controlling the cellular compositions and protection against immune rejection may be addressed by genetic modifications of SC-ß pre-transplantation. To screen for gene targets, we have generated a human embryonic stem cell line (hESC) that constitutively express the enhanced specificity Streptococcus pyogenes Cas9 (eSpCas9) gene, knocked-in into the GAPDH locus.

Dynamical Localization Simulated on Actual Quantum Hardware.

Quantum computers are invaluable tools to explore the properties of complex quantum systems. We show that dynamical localization of the quantum sawtooth map, a highly sensitive quantum coherent phenomenon, can be simulated on actual, small-scale quantum processors. Our results demonstrate that quantum computing of dynamical localization may become a convenient tool for evaluating advances in quantum hardware performances.

Generation of a heterozygous GAPDH-Luciferase human ESC line (HVRDe008-A-1) for in vivo monitoring of stem cells and their differentiated progeny.

Human stem cell-derived beta (SC-ß) cells are a candidate for cell replacement therapy for type 1 diabetes. Whilst refinements to the differentiation protocol have resulted in the production of SC-ß cells that resemble adult beta cells, the unsolved challenge to protect transplanted SC-ß cells from the host immune system remains. To monitor the survival of SC-ß cells in vivo, we knocked-in the Firefly luciferase gene into the GAPDH locus of the HUES8 human embryonic stem cell (hESC) line, such that differentiated islet cells constitutively express luciferase.

Machine learning workflows identify a microRNA signature of insulin transcription in human tissues.

Dicer knockout mouse models demonstrated a key role for microRNAs in pancreatic ß-cell function. Studies to identify specific microRNA(s) associated with human (pro-)endocrine gene expression are needed. We profiled microRNAs and key pancreatic genes in 353 human tissue samples. Machine learning workflows identified microRNAs associated with (pro-)insulin transcripts in a discovery set of islets (n = 30) and insulin-negative tissues (n = 62). This microRNA signature was validated in remaining 261 tissues that include nine islet samples from individuals with type 2 diabetes. Top eight microRNAs (miR-183-5p, -375-3p, 216b-5p, 183-3p, -7-5p, -217-5p, -7-2-3p, and -429-3p) were confirmed to be associated with and predictive of (pro-)insulin transcript levels. Use of doxycycline-inducible microRNA-overexpressing human pancreatic duct cell lines confirmed the regulatory roles of these microRNAs in (pro-)endocrine gene expression. Knockdown of these microRNAs in human islet cells reduced (pro-)insulin transcript abundance. Our data provide specific microRNAs to further study microRNA-mRNA interactions in regulating insulin transcription.

Doubly-Resonant Photonic Crystal Cavities for Efficient Second-Harmonic Generation in III-V Semiconductors.

Second-order nonlinear effects, such as second-harmonic generation, can be strongly enhanced in nanofabricated photonic materials when both fundamental and harmonic frequencies are spatially and temporally confined. Practically designing low-volume and doubly-resonant nanoresonators in conventional semiconductor compounds is challenging owing to their intrinsic refractive index dispersion. In this work we review a recently developed strategy to design doubly-resonant nanocavities with low mode volume and large quality factor via localized defects in a photonic crystal structure. We built on this approach by applying an evolutionary optimization algorithm in connection with Maxwell equations solvers; the proposed design recipe can be applied to any material platform. We explicitly calculated the second-harmonic generation efficiency for doubly-resonant photonic crystal cavity designs in typical III-V semiconductor materials, such as GaN and AlGaAs, while targeting a fundamental harmonic at telecom wavelengths and fully accounting for the tensor nature of the respective nonlinear susceptibilities. These results may stimulate the realization of small footprint photonic nanostructures in leading semiconductor material platforms to achieve unprecedented nonlinear efficiencies.

Metasurface Integrated Monolayer Exciton Polariton.

Monolayer transition-metal dichalcogenides (TMDs) are the first truly two-dimensional (2D) semiconductor, providing an excellent platform to investigate light-matter interaction in the 2D limit. The inherently strong excitonic response in monolayer TMDs can be further enhanced by exploiting the temporal confinement of light in nanophotonic structures. Here, we demonstrate a 2D exciton-polariton system by strongly coupling atomically thin tungsten diselenide (WSe2) monolayer to a silicon nitride (SiN) metasurface. Via energy-momentum spectroscopy of the WSe2-metasurface system, we observed the characteristic anticrossing of the polariton dispersion both in the reflection and photoluminescence spectrum. A Rabi splitting of 18 meV was observed which matched well with our numerical simulation. Moreover, we showed that the Rabi splitting, the polariton dispersion, and the far-field emission pattern could be tailored with subwavelength-scale engineering of the optical meta-atoms. Our platform thus opens the door for the future development of novel, exotic exciton-polariton devices by advanced meta-optical engineering.

Tailoring Dispersion of Room-Temperature Exciton-Polaritons with Perovskite-Based Subwavelength Metasurfaces.

Exciton-polaritons represent a promising platform for studying quantum fluids of light and realizing prospective all-optical devices. Here we report on the experimental demonstration of exciton-polaritons at room temperature in resonant metasurfaces made from a sub-wavelength two-dimensional lattice of perovskite pillars. The strong coupling regime is revealed by both angular-resolved reflectivity and photoluminescence measurements, showing anticrossing between photonic modes and the exciton resonance with a Rabi splitting in the 200 meV range. Moreover, by tailoring the photonic Bloch mode to which perovskite excitons are coupled, polaritonic dispersions are engineered exhibiting linear, parabolic, and multivalley dispersions. All of our results are perfectly reproduced by both numerical simulations based on a rigorous coupled wave analysis and an elementary model based on a quantum theory of radiation-matter interaction. Our results suggest a new approach to study exciton-polaritons and pave the way toward large-scale and low-cost integrated polaritonic devices operating at room temperature.

Charging a quantum battery via nonequilibrium heat current.

When a quantum system is subject to a thermal gradient it may sustain a steady nonequilibrium heat current by entering into a so-called nonequilibrium steady state (NESS). Here we show that NESS constitute a thermodynamic resource that can be exploited to charge a quantum battery. This adds to the list of recently reported sources available at the nanoscale, such as coherence, entanglement, and quantum measurements. We elucidate this concept by showing analytic and numerical studies of a two-qubit quantum battery that is alternatively charged by an incoherent heat flow and discharged by application of a properly chosen unitary gate. The presence of a NESS for the charging step guarantees steady operation with positive power output. Decreasing the duration of the charging step results in a time-periodic steady state accompanied by increased efficiency and output power. The device is amenable to implementation with different nanotechnology platforms.

Optimal efficiency of the Q-cycle mechanism around physiological temperatures from an open quantum systems approach.

The Q-cycle mechanism entering the electron and proton transport chain in oxygenic photosynthesis is an example of how biological processes can be efficiently investigated with elementary microscopic models. Here we address the problem of energy transport across the cellular membrane from an open quantum system theoretical perspective. We model the cytochrome [Formula: see text] protein complex under cyclic electron flow conditions starting from a simplified kinetic model, which is hereby revisited in terms of a Markovian quantum master equation formulation and spin-boson Hamiltonian treatment. We apply this model to theoretically demonstrate an optimal thermodynamic efficiency of the Q-cycle around ambient and physiologically relevant temperature conditions. Furthermore, we determine the quantum yield of this complex biochemical process after setting the electrochemical potentials to values well established in the literature. The present work suggests that the theory of quantum open systems can successfully push forward our theoretical understanding of complex biological systems working close to the quantum/classical boundary.

Luciferase-based reporting of suicide gene activity in murine mesenchymal stem cells.

Due to their ease of isolation, gene modification and tumor-homing properties, mesenchymal stem cells (MSCs) are an attractive cellular vehicle for the delivery of toxic suicide genes to a variety of cancers in pre-clinical models. In addition, the incorporation of suicide genes in stem cell-derived cell replacement therapies improves their safety profile by permitting graft destruction in the event of unexpected tumorigeneses or unwanted differentiation. Due to the functional requirement of ATP for the Firefly luciferase gene Luc2 to produce light, luciferase-based reporting of cytotoxicity can be engineered into potential cell therapies. Consequently, we nucleofected mammalian expression plasmids containing both the Luc2 and the yeast fusion cytosine deaminase uracil phosphoribosyltransferase (CDUPRT) genes for expression in murine MSCs to assess luciferase as a reporter of suicide gene cytotoxicity, and MSC as vehicles of suicide gene therapy. In vitro bioluminescence imaging (BLI) showed that following the addition of the non-toxic prodrug fluorocytosine (5-FC), CDUPRT-expressing MSCs displayed enhanced cytotoxicity in comparison to Luc2 reporter MSC controls. This study demonstrates the utility of luciferase as a reporter of CDUPRT-mediated cytotoxicity in murine MSC using BLI.

High-Efficiency Lentiviral Gene Modification of Primary Murine Bone-Marrow Mesenchymal Stem Cells.

Lentiviral vectors are the method of choice for stable gene modification of a variety of cell types. However, the efficiency with which they transduce target cells varies significantly, in particular their typically poor capacity to transduce primary stem cells. Here we describe the isolation and enrichment of murine bone-marrow mesenchymal stem cells (MSCs) via fluorescence-activated cell sorting (FACS); the cloning, production, and concentration of high-titer second generation lentiviral vectors via combined tangential flow filtration (TFF) and ultracentrifugation; and the subsequent high-efficiency gene modification of MSCs into insulin-producing cells via overexpression of the furin-cleavable human insulin (INS-FUR) gene.

Ex Vivo Expansion of Murine MSC Impairs Transcription Factor-Induced Differentiation into Pancreatic ß-Cells.

Combinatorial gene and cell therapy as a means of generating surrogate ß-cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification ex vivo, mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine. To overcome the aforementioned limitation of current therapies, we assessed the utility of ex vivo expanded bone marrow-derived murine MSCs for their persistence in immune-competent and immune-deficient animal models and their ability to differentiate into surrogate ß-cells. CD45-/Ly6+ murine MSCs were isolated from the bone marrow of nonobese diabetic (NOD) mice and nucleofected to express the bioluminescent protein, Firefly luciferase (Luc2). The persistence of a subcutaneous (s.c.) transplant of Luc2-expressing MSCs was assessed in immune-competent (NOD) (n = 4) and immune-deficient (NOD/Scid) (n = 4) animal models of diabetes. Luc2-expressing MSCs persisted for 2 and 12 weeks, respectively, in NOD and NOD/Scid mice. Ex vivo expanded MSCs were transduced with the HMD lentiviral vector (MOI = 10) to express furin-cleavable human insulin (INS-FUR) and murine NeuroD1 and Pdx1. This was followed by the characterization of pancreatic transdifferentiation via reverse transcriptase polymerase chain reaction (RT-PCR) and static and glucose-stimulated insulin secretion (GSIS). INS-FUR-expressing MSCs were assessed for their ability to reverse diabetes after transplantation into streptozotocin- (STZ-) diabetic NOD/Scid mice (n = 5). Transduced MSCs did not undergo pancreatic transdifferentiation, as determined by RT-PCR analyses, lacked glucose responsiveness, and upon transplantation did not reverse diabetes. The data suggest that ex vivo expanded MSCs lose their multipotent differentiation potential and may be more useful as gene therapy targets prior to expansion.