Witnessing Optomechanical Entanglement with Photon Counting.

The ability to coherently control mechanical systems with optical fields has made great strides over the past decade, and now includes the use of photon counting techniques to detect the nonclassical nature of mechanical states. These techniques may soon be used to perform an optomechanical Bell test, hence highlighting the potential of cavity optomechanics for device-independent quantum information processing. Here, we propose a witness which reveals optomechanical entanglement without any constraint on the global detection efficiencies in a setup allowing one to test a Bell inequality. While our witness relies on a well-defined description and correct experimental calibration of the measurements, it does not need a detailed knowledge of the functioning of the optomechanical system. A feasibility study including dominant sources of noise and loss shows that it can readily be used to reveal optomechanical entanglement in present-day experiments with photonic crystal nanobeam resonators.

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abl1, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis. BC-CML is often associated with excessive phosphorylated eukaryotic translation initiation factor 4E (eIF4E), which renders LSCs capable of proliferating via self-renewal, oblivious to BCR-ABL1 inhibition. In vivo, eIF4E is exclusively phosphorylated on Ser209 by MNK1/2. Consequently, a selective inhibitor of MNK1/2 should reduce the level of phosphorylated eIF4E and re-sensitize LSCs to BCR-ABL1 inhibition, thus hindering the proliferation of BC LSCs. We report herein the structure-activity relationships and pharmacokinetic properties of a selective MNK1/2 inhibitor clinical candidate, ETC-206, which in combination with dasatinib prevents BC-CML LSC self-renewal in vitro and enhances dasatinib antitumor activity in vivo.

Generation of single photons with highly tunable wave shape from a cold atomic ensemble.

The generation of ultra-narrowband, pure and storable single photons with widely tunable wave shape is an enabling step toward hybrid quantum networks requiring interconnection of remote disparate quantum systems. It allows interaction of quantum light with several material systems, including photonic quantum memories, single trapped ions and opto-mechanical systems. Previous approaches have offered a limited tuning range of the photon duration of at most one order of magnitude. Here we report on a heralded single photon source with controllable emission time based on a cold atomic ensemble, which can generate photons with temporal durations varying over three orders of magnitude up to 10 µs without a significant change of the readout efficiency. We prove the nonclassicality of the emitted photons, show that they are emitted in a pure state, and demonstrate that ultra-long photons with nonstandard wave shape can be generated, which are ideally suited for several quantum information tasks.

Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells.

Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure-activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented.

Probing the binding mechanism of Mnk inhibitors by docking and molecular dynamics simulations.

Mitogen-activated protein kinases-interacting kinase 1 and 2 (Mnk1/2) activate the oncogene eukaryotic initiation factor 4E (eIF4E) by phosphorylation. High level of phosphorylated eIF4E is associated with various types of cancers. Inhibition of Mnk prevents eIF4E phosphorylation, making them potential therapeutic targets for cancer. Recently, we have designed and synthesized a series of novel imidazopyridine and imidazopyrazine derivatives that inhibit Mnk1/2 kinases with a potency in the nanomolar to micromolar range. In the current work we model the inhibition of Mnk kinase activity by these inhibitors using various computational approaches. Combining homology modeling, docking, molecular dynamics simulations, and free energy calculations, we find that all compounds bind similarly to the active sites of both kinases with their imidazopyridine and imidazopyrazine cores anchored to the hinge regions of the kinases through hydrogen bonds. In addition, hydrogen bond interactions between the inhibitors and the catalytic Lys78 (Mnk1), Lys113 (Mnk2) and Ser131 (Mnk1), Ser166 (Mnk2) appear to be important for the potency and stability of the bound conformations of the inhibitors. The computed binding free energies (ΔGPred) of these inhibitors are in accord with experimental bioactivity data (pIC50) with correlation coefficients (r(2)) of 0.70 and 0.68 for Mnk1 and Mnk2 respectively. van der Waals energies and entropic effects appear to dominate the binding free energy (ΔGPred) for each Mnk-inhibitor complex studied. The models suggest that the activities of these small molecule inhibitors arise from interactions with multiple residues in the active sites, particularly with the hydrophobic residues.

Witnessing trustworthy single-photon entanglement with local homodyne measurements.

Single-photon entangled states, i.e., states describing two optical paths sharing a single photon, constitute the simplest form of entanglement. Yet they provide a valuable resource in quantum information science. Specifically, they lie at the heart of quantum networks, as they can be used for quantum teleportation, swapped, and purified with linear optics. The main drawback of such entanglement is the difficulty in measuring it. Here, we present and experimentally test an entanglement witness allowing one to say whether a given state is path entangled and also that entanglement lies in the subspace, where the optical paths are each filled with one photon at most, i.e., refers to single-photon entanglement. It uses local homodyning only and relies on no assumption about the Hilbert space dimension of the measured system. Our work provides a simple and trustworthy method for verifying the proper functioning of future quantum networks.

Device-independent certification of entangled measurements.

We present a device-independent protocol to test if a given black-box measurement device is entangled, that is, has entangled eigenstates. Our scheme involves three parties and is inspired by entanglement swapping; the test uses the Clauser-Horne-Shimony-Holt Bell inequality, checked between each pair of parties. In the case where all particles are qubits, we characterize quantitatively the deviation of the measurement device from a perfect Bell-state measurement.