A 16-parts-per-trillion measurement of the antiproton-to-proton charge-mass ratio.

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

Direct limits on the interaction of antiprotons with axion-like dark matter.

Astrophysical observations indicate that there is roughly five times more dark matter in the Universe than ordinary baryonic matter1, and an even larger amount of the Universe's energy content is attributed to dark energy2. However, the microscopic properties of these dark components remain unknown. Moreover, even ordinary matter-which accounts for five per cent of the energy density of the Universe-has yet to be understood, given that the standard model of particle physics lacks any consistent explanation for the predominance of matter over antimatter3. Here we present a direct search for interactions of antimatter with dark matter and place direct constraints on the interaction of ultralight axion-like particles (dark-matter candidates) with antiprotons. If antiprotons have a stronger coupling to these particles than protons do, such a matter-antimatter asymmetric coupling could provide a link between dark matter and the baryon asymmetry in the Universe. We analyse spin-flip resonance data in the frequency domain acquired with a single antiproton in a Penning trap4 to search for spin-precession effects from ultralight axions, which have a characteristic frequency governed by the mass of the underlying particle. Our analysis constrains the axion-antiproton interaction parameter to values greater than 0.1 to 0.6 gigaelectronvolts in the mass range from 2 × 10-23 to 4 × 10-17 electronvolts, improving the sensitivity by up to five orders of magnitude compared with astrophysical antiproton bounds. In addition, we derive limits on six combinations of previously unconstrained Lorentz- and CPT-violating terms of the non-minimal standard model extension5.

Measurement of Ultralow Heating Rates of a Single Antiproton in a Cryogenic Penning Trap.

We report on the first detailed study of motional heating in a cryogenic Penning trap using a single antiproton. Employing the continuous Stern-Gerlach effect we observe cyclotron quantum transition rates of 6(1) quanta/h and an electric-field noise spectral density below 7.5(3.4)×10^{-20} V^{2} m^{-2} Hz^{-1}, which corresponds to a scaled noise spectral density below 8.8(4.0)×10^{-12} V^{2} m^{-2}, results which are more than 2 orders of magnitude smaller than those reported by other ion-trap experiments.

Single crystal Er3+ : YAG fibers with tailored refractive index profiles.

Erbium-doped yttrium aluminum garnet (Er3+:YAG) rods were inserted inside undoped tubes and grown into single-crystal fibers of a diameter of 300 µm using the laser-heated pedestal growth technique. Growth at various rates resulted in radially graded distributions of Er3+ dopant ions, as observed using laser-induced fluorescence imaging. Profiles of the refractive index were measured using cross-sectional reflectometry in a microscope. Dopant distributions and the corresponding index profiles were compared with thermal diffusion theory to determine the inter-diffusion coefficient of Y3+ and Er3+ ions at 2000°C, yielding an estimated value of D=(9.10±0.8)×10-11 m2/s. This work constitutes a step toward controlled growth of fibers with high thermal conductivities, low Brillouin gain, and waveguiding properties required for high-power optical amplifier and laser applications.

Early Phase Clinical Trial Designs - State of Play and Adapting for the Future.

The process of anti-cancer drug development is complex, with high attrition rates. Factors that may optimise this process include well-constructed and relevant pre-clinical testing and use of biomarkers for patient selection. However, the design of early phase clinical trials will probably play a vital role in both the robust clinical investigation of new targeted therapies and in streamlining drug development. In this overview, we assess current concepts in phase I clinical trials, highlighting issues and opportunities to improve their meaningfulness. The particular challenge of how to design combination trials is addressed, with focus on the potential of new adaptive and model-based designs.

A parts-per-billion measurement of the antiproton magnetic moment.

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton µN with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result = -2.7928473441(42)µN (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, µp = 2.792847350(9)µN, and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10-12 Bohr magnetons.

Investigation of hollow cylindrical metal terahertz waveguides suitable for cryogenic environments.

The field of terahertz (THz) waveguides continues to grow rapidly, with many being tailored to suit the specific demands of a particular final application. Here, we explore waveguides capable of enabling efficient and accurate power delivery within cryogenic environments (< 4 K). The performance of extruded hollow cylindrical metal waveguides made of un-annealed and annealed copper, as well as stainless steel, have been investigated for bore diameters between 1.75 - 4.6 mm, and at frequencies of 2.0, 2.85 and 3.4 THz, provided by a suitable selection of THz quantum cascade lasers. The annealed copper resulted in the lowest transmission losses, < 3 dB/m for a 4.6 mm diameter waveguide, along with 90° bending losses as low as ~2 dB for a bend radius of 15.9 mm. The observed trends in losses were subsequently analyzed and related to measured inner surface roughness parameters. These results provide a foundation for the development of a wide array of demanding low-temperature THz applications, and enabling the study of fundamental physics.

Efficient coupling of double-metal terahertz quantum cascade lasers to flexible dielectric-lined hollow metallic waveguides.

The growth in terahertz frequency applications utilising the quantum cascade laser is hampered by a lack of targeted power delivery solutions over large distances (>100 mm). Here we demonstrate the efficient coupling of double-metal quantum cascade lasers into flexible polystyrene lined hollow metallic waveguides via the use of a hollow copper waveguide integrated into the laser mounting block. Our approach exhibits low divergence, Gaussian-like emission, which is robust to misalignment error, at distances > 550 mm, with a coupling efficiency from the hollow copper waveguide into the flexible waveguide > 90%. We also demonstrate the ability to nitrogen purge the flexible waveguide, increasing the power transmission by up to 20% at 2.85 THz, which paves the way for future fibre based terahertz sensing and spectroscopy applications.

Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells.

BACKGROUND: Amplification of aurora kinase A (AK-A) overrides the mitotic spindle assembly checkpoint, inducing resistance to taxanes. RNA interference targeting AK-A in human pancreatic cancer cell lines enhanced taxane chemosensitivity. In this study, a novel AK-A inhibitor, CYC3, was investigated in pancreatic cancer cell lines, in combination with paclitaxel. METHODS: Western blot, flow cytometry and immunostaining were used to investigate the specificity of CYC3. Sulforhodamine B staining, time-lapse microscopy and colony-formation assays were employed to evaluate the cytotoxic effect of CYC3 and paclitaxel. Human colony-forming unit of granulocyte and macrophage (CFU-GM) cells were used to compare the effect in tumour and normal tissue. RESULTS: CYC3 was shown to be a specific AK-A inhibitor. Three nanomolar paclitaxel (growth inhibition 50% (GI(50)) 3 nM in PANC-1, 5.1 nM in MIA PaCa-2) in combination with 1 µM CYC3 (GI(50) 1.1 µM in MIA PaCa2 and 2 µM in PANC-1) was synergistic in inhibiting pancreatic cell growth and causing mitotic arrest, achieving similar effects to 10-fold higher concentrations of paclitaxel (30 nM). In CFU-GM cells, the effect of the combination was simply additive, displaying significantly less myelotoxicity compared with high concentrations of paclitaxel (30 nM; 60-70% vs 100% inhibition). CONCLUSION: The combination of lower doses of paclitaxel and CYC3 merits further investigation with the potential for an improved therapeutic index in vivo.

Management of metastatic castration-resistant prostate cancer after first-line docetaxel.

Although chemotherapy, based on docetaxel, is now established in the management of metastatic castration-resistant prostate cancer (mCRPC), until recently, there has been no treatment licensed for use in the second line in men whose disease progresses during or after docetaxel therapy. This article reviews the classes of agents that have shown potential in this setting, notably chemotherapy drugs, hormonal therapies, immunotherapies, anti-angiogenic drugs, and clusterin-targeted therapy.

Hollow-glass waveguide delivery of an infrared free-electron laser for microsurgical applications.

The purpose of this research is to deliver free-electron-laser (FEL) pulses for intraocular microsurgery. The FEL at Vanderbilt University is tunable from 1.8 to 10.8 microm. To deliver the FEL beam we used a metallic-coated hollow-glass waveguide of 530-mum inner diameter. A 20-gauge cannula with a miniature CaF2 window shielded the waveguide from water. Open-sky retinotomy was performed on cadaver eyes. The system delivered as much as 6 x 10(5) W of FEL peak power to the intraocular tissues without damage to the waveguide or to the surgical probe.

Art or science? Understanding medicine and the common law.

Those of you who have either had or seen the process of a magnetic resonance imaging (MRI) scan cannot fail to be impressed with the scientific or technologic marvel of this huge diagnostic machinery. After a relatively noisy series of manoeuvres, the machine turns out a beautiful set of images on film. That is the science. What happens next, though, is that the films are given to a radiologist who gazes at them, puzzles for awhile and then gives an opinion on what they might mean. That is the art.

Processing and characterization of silver films used to fabricate hollow glass waveguides.

Hollow glass waveguides are an increasingly popular fiber for the delivery of high-power IR laser radiation. At CO(2) laser wavelengths the measured and theoretical losses agree, but at the 3-microm Er:YAG laser wavelength the losses remain higher than expected. The reason for this is the surface roughness of the silver film used to form the first layer of the Ag/AgI thin-film structure. We found that the roughness of the silver film increases fivefold as silvering times increase from 5 to 80 min. This increased surface roughness produces a concomitant linear increase in the attenuation coefficient for the silver-only guides for wavelengths shorter than approximately 5 microm.

Single-Crystal Laser-Heated Pedestal-Growth Sapphire Fibers for Er:YAG Laser Power Delivery.

The Er:YAG laser-induced damage (LID) threshold and modal properties of single-crystal sapphire fibers grown by the laser-heated pedestal-growth method have been measured. The lowest loss (~0.4-dB/m) sapphire fibers produce little mode mixing and therefore deliver a near-single-mode output profile if the Er:YAG laser input beam profile is also nearly Gaussian. Normally, however, Er:YAG laser output beam profiles are multimode with numerous high-energy spikes. This leads not only to a multimode output from the fiber but also increased fiber loss that is due to higher-order mode coupling. The results of LID testing give a damage fluence of ~1.4 kJ/cm(2) for 300-mum core-only sapphire fibers at 2.94 mum.

Optical properties of single-crystal sapphire fibers.

Single-crystal sapphire fibers have been grown with the laser-heated pedestal-growth method with losses as low as 0.3 dB /m at 2.94 ?m. With the incorporation of a computer-controlled feedback system, fibers have been grown with less than +/-0.5 % diameter variation, or +/-1.5 ?m for a 300- ?m fiber. The losses in these fibers have been reduced further through a postgrowth anneal at 1000 degrees C in air, from 5.4 to 1.5 dB /m at 543 nm and from 0.4 -0.3 dB /m at 2.94 ?m. These fibers delivered 4.7 W at 10 Hz of Er:YAG laser power.

High-peak-power, pulsed CO(2) laser light delivery by hollow glass waveguides.

Flexible hollow glass waveguides with internal metallic and dielectric coatings have been used to deliver high-peak-power transversely excited atmosphere CO(2) laser energy. The straight guide loss is as low as 0.17 dB/m for 1000-mum-bore guides and 0.46 dB/m for 530-mum-bore guides propagating the HE(11) mode. The loss increases to 0.93 and 1.36 dB/m, respectively, when guides are bent to a radius of 0.25 m. The hollow glass waveguides have been used to deliver pulsed CO(2) laser energy successfully with a peak power of 0.7 MW and an energy of 350 mJ per pulse with a gas purge through the hollow core. The delivered average power is as high as 27 W. It is concluded that these waveguides are promising candidates for pulsed CO(2) laser delivery in medical and surgical applications.

Hollow-waveguide delivery systems for high-power, industrial CO(2) lasers.

Hollow-sapphire and metal-dielectric-coated hollow-glass waveguides have been used to deliver CO(2) laser power for industrial laser applications. The transmission, bending loss, and output-beam properties of these waveguides are described. The bore sizes of the hollow-sapphire waveguides were 1070 and 790 µm, and the hollow-glass waveguide had a bore of 700 µm. The waveguides ranged in length from 1.1 to 1.5 m. The sapphire waveguides were bent to 90°, and the hollow-glass waveguides were bent into a full 360° loop. We delivered a maximum of 1.8 kW through the 1070-µm-bore sapphire waveguide and 1.0 kW through the hollow-glass waveguide. All the hollow waveguides incorporated a water jacket to prevent overheating.

Small-bore hollow waveguides for delivery of 3-µm laser radiation.

Flexible hollow glass waveguides with bore diameters as small as 250 µm have been developed for 3-µm laser delivery. All the guides exhibit straight losses between 0.10 and 1.73 dB/m, and the loss increases to between 2.4 and 5.1 dB/m upon bending 1 m of the guides into 15-cm-diameter coils. This behavior is shown to depend strongly on the launch conditions and mode quality of the input beam. The waveguides are capable of efficiently delivering up to 8 W of Er:YAG laser power with proper input coupling, and they are suitable for use in both medical and industrial applications.