Pharmacological Activation of PDC Flux Reverses Lipid-Induced Inhibition of Insulin Action in Muscle During Recovery From Exercise.

Insulin resistance is a risk factor for type 2 diabetes, and exercise can improve insulin sensitivity. However, following exercise, high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a crossover design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemic-euglycemic clamp 5 h after one-legged exercise with 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC activator, dichloroacetate (DCA). Intralipid infusion reduced insulin-stimulated glucose uptake by 19% in the previously exercised leg, which was not observed in the contralateral rested leg. Interestingly, this effect of intralipid in the exercised leg was abolished by DCA, which increased muscle PDC activity (130%) and flux (acetylcarnitine 130%) and decreased inhibitory phosphorylation of PDC on Ser293 (∼40%) and Ser300 (∼80%). Novel insight is provided into the regulatory interaction between glucose and lipid metabolism during exercise recovery. Coupling exercise and PDC flux activation upregulated the capacity for both glucose transport (exercise) and oxidation (DCA), which seems necessary to fully stimulate insulin-stimulated glucose uptake during recovery.

Dual-axis cubic cavity for drift-compensated multi-wavelength laser stabilisation.

We describe a 'clock control unit' based on a dual-axis cubic cavity (DACC) for the frequency stabilisation of lasers involved in a strontium optical lattice clock. The DACC, which ultimately targets deployment in space applications, provides a short-term stable reference for all auxiliary lasers-i.e. cooling, clear-out, and optical lattice-in a single multi-band cavity. Long-term cavity drift is compensated by a feed-forward scheme exploiting a fixed physical relation to an orthogonal second cavity axis; either by reference to an ultrastable 698 nm clock laser, or by exploiting the differential drift between orthogonal axes extracted by a single laser in common view. Via a change of mirror set in the cavity axis accessed by the clock laser, the system could also provide stabilisation for sub-Hz linewidths at the 698 nm clock wavelength, fulfilling all stabilisation requirements of the clock.

Cavity-enhanced non-destructive detection of atoms for an optical lattice clock.

We demonstrate a new method of cavity-enhanced non-destructive detection of atoms for a strontium optical lattice clock. The detection scheme is shown to be linear in atom number up to at least 2×104 atoms, to reject technical noise sources, to achieve signal to noise ratio close to the photon shot noise limit, to provide spatially uniform atom-cavity coupling, and to minimize inhomogeneous ac Stark shifts. These features enable detection of atoms with minimal perturbation to the atomic state, a critical step towards realizing an ultra-high-stability, quantum-enhanced optical lattice clock.

A pyramid MOT with integrated optical cavities as a cold atom platform for an optical lattice clock.

We realize a two-stage, hexagonal pyramid magneto-optical trap (MOT) with strontium, and demonstrate loading of cold atoms into cavity-enhanced 1D and 2D optical lattice traps, all within a single compact assembly of in-vacuum optics. We show that the device is suitable for high-performance quantum technologies, focusing especially on its intended application as a strontium optical lattice clock. We prepare 2 × 104 spin-polarized atoms of 87Sr in the optical lattice within 500 ms; we observe a vacuum-limited lifetime of atoms in the lattice of 27 s; and we measure a background DC electric field of 12 V m-1 from stray charges, corresponding to a fractional frequency shift of (-1.2 ± 0.8) × 10-18 to the strontium clock transition. When used in combination with careful management of the blackbody radiation environment, the device shows potential as a platform for realizing a compact, robust, transportable optical lattice clock with systematic uncertainty at the 10-18 level.

A scalable arbitrary waveform generator for atomic physics experiments based on field-programmable gate array technology.

We present a field-programmable gate array (FPGA) based control system that has been implemented to control a strontium optical lattice clock at the National Physical Laboratory, UK. Bespoke printed circuit boards have been designed and manufactured, including an 8-channel, 16-bit digital to analog converter board with a 2 µs update rate and a 4-channel direct-digital synthesis board clocked at 1 GHz. Each board includes its own FPGA with 28 digital output lines available alongside the specialized analog or radio frequency outputs. The system is scalable to a large number of control lines by stacking the individual boards in a master-slave arrangement. The timing of the digital and analog outputs is based on the FPGA clock and is thus very predictable and exhibits low jitter. A particular advantage of our hardware is its large data buffers that, when combined with a pseudoclock structure, allow complex waveforms to be created. A high reliability of the system has been demonstrated during extended atomic clock frequency comparisons.

State of the art of guidelines.

Guidelines have existed in medicine for many centuries. Galen's doctrine of laudable pus sent many to an early grave, but variance in treatment put the practitioner in a difficult position, especially if all did not go well. Currently, guidelines proliferate, allegedly based upon careful evaluation of evidence culled from a variety of sources. However, obedience to guidelines is variable internationally and nationally, thus raising questions about their enforceability. They are, of course, not legally enforceable, but courts may be influenced by them, and variation must be evidence-based. Guidelines cannot logically be regarded as being set in stone; if that were the case, then there could be no innovation and medicine would not advance.