Mode mixing and losses in misaligned microcavities.

We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.

An optically heated atomic source for compact ion trap vacuum systems.

We present a design for an atomic oven suitable for loading ion traps, which is operated via optical heating with a continuous-wave multimode diode laser. The absence of the low-resistance electrical connections necessary for Joule heating allows the oven to be extremely well thermally isolated from the rest of the vacuum system. Extrapolating from high-flux measurements of an oven filled with calcium, we calculate that a target region number density of 100 cm-3, suitable for rapid ion loading, will be produced with 175(10) mW of heating laser power, limited by radiative losses. With simple feedforward to the laser power, the turn-on time for the oven is 15 s. Our measurements indicate that an oven volume 1000 times smaller could still hold enough source metal for decades of continuous operation.

High-Rate, High-Fidelity Entanglement of Qubits Across an Elementary Quantum Network.

We demonstrate remote entanglement of trapped-ion qubits via a quantum-optical fiber link with fidelity and rate approaching those of local operations. Two ^{88}Sr^{+} qubits are entangled via the polarization degree of freedom of two spontaneously emitted 422 nm photons which are coupled by high-numerical-aperture lenses into single-mode optical fibers and interfere on a beam splitter. A novel geometry allows high-efficiency photon collection while maintaining unit fidelity for ion-photon entanglement. We generate heralded Bell pairs with fidelity 94% at an average rate 182 s^{-1} (success probability 2.18×10^{-4}).

Probing Qubit Memory Errors at the Part-per-Million Level.

Robust qubit memory is essential for quantum computing, both for near-term devices operating without error correction, and for the long-term goal of a fault-tolerant processor. We directly measure the memory error ε_{m} for a ^{43}Ca^{+} trapped-ion qubit in the small-error regime and find ε_{m}<10^{-4} for storage times t≲50 ms. This exceeds gate or measurement times by three orders of magnitude. Using randomized benchmarking, at t=1 ms we measure ε_{m}=1.2(7)×10^{-6}, around ten times smaller than that extrapolated from the T_{2}^{*} time, and limited by instability of the atomic clock reference used to benchmark the qubit.

A short response time atomic source for trapped ion experiments.

Ion traps are often loaded from atomic beams produced by resistively heated ovens. We demonstrate an atomic oven which has been designed for fast control of the atomic flux density and reproducible construction. We study the limiting time constants of the system and, in tests with 40Ca, show that we can reach the desired level of flux in 12 s, with no overshoot. Our results indicate that it may be possible to achieve an even faster response by applying an appropriate one-off heat treatment to the oven before it is used.

Cell cycle-coupled expansion of AR activity promotes cancer progression.

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

Resolved-Sideband Laser Cooling in a Penning Trap.

We report the laser cooling of a single ^{40}Ca^{+} ion in a Penning trap to the motional ground state in one dimension. Cooling is performed in the strong binding limit on the 729-nm electric quadrupole S_{1/2}↔D_{5/2} transition, broadened by a quench laser coupling the D_{5/2} and P_{3/2} levels. We find the final ground-state occupation to be 98(1)%. We measure the heating rate of the trap to be very low with n[over ¯][over ˙]≈0.3(2) s^{-1} for trap frequencies from 150-400 kHz, consistent with the large ion-electrode distance.

Targeting cell cycle and hormone receptor pathways in cancer.

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability of PD to function in the presence of existing hormone-based regimens and to cooperate with ionizing radiation to further suppress cellular growth. Importantly, it was determined that PD is a critical mediator of PD action. The anti-proliferative impact of CDK4/6 inhibition was revealed through reduced proliferation and delayed growth using PCa cell xenografts. Finally, first-in-field effects of PD on proliferation were observed in primary human prostatectomy tumor tissue explants. This study shows that selective CDK4/6 inhibition, using PD either as a single-agent or in combination, hinders key proliferative pathways necessary for disease progression and that RB status is a critical prognostic determinant for therapeutic efficacy. Combined, these pre-clinical findings identify selective targeting of CDK4/6 as a bona fide therapeutic target in both early stage and advanced PCa and underscore the benefit of personalized medicine to enhance treatment response.