Efficient Large-Scale, Targeted Gravitational-Wave Probes of Supermassive Black-Hole Binaries.

Binary systems of supermassive black holes are promising sources of low-frequency gravitational waves (GWs) and bright electromagnetic emission. Pulsar timing array GW searches for individual binaries have been limited to only a few candidate systems due to computational demands, which get worse as more pulsars are added. By modeling the GW signal using only components from when the GW passes Earth (rather than also each pulsar), we find constraints on the binary's total mass and GW frequency that are similar to a full signal analysis, yet ∼70 times more efficient.

Constraining Alternative Theories of Gravity Using Pulsar Timing Arrays.

The opening of the gravitational wave window by ground-based laser interferometers has made possible many new tests of gravity, including the first constraints on polarization. It is hoped that, within the next decade, pulsar timing will extend the window by making the first detections in the nanohertz frequency regime. Pulsar timing offers several advantages over ground-based interferometers for constraining the polarization of gravitational waves due to the many projections of the polarization pattern provided by the different lines of sight to the pulsars, and the enhanced response to longitudinal polarizations. Here, we show that existing results from pulsar timing arrays can be used to place stringent limits on the energy density of longitudinal stochastic gravitational waves. However, unambiguously distinguishing these modes from noise will be very difficult due to the large variances in the pulsar-pulsar correlation patterns. Existing upper limits on the power spectrum of pulsar timing residuals imply that the amplitude of vector longitudinal (VL) and scalar longitudinal (SL) modes at frequencies of 1/year are constrained, A_{VL}<4×10^{-16} and A_{SL}<4×10^{-17}, while the bounds on the energy density for a scale invariant cosmological background are Ω_{VL}h^{2}<4×10^{-11} and Ω_{SL}h^{2}<3×10^{-13}.

Constraints on the Dynamical Environments of Supermassive Black-Hole Binaries Using Pulsar-Timing Arrays.

We introduce a technique for gravitational-wave analysis, where Gaussian process regression is used to emulate the strain spectrum of a stochastic background by training on population-synthesis simulations. This leads to direct Bayesian inference on astrophysical parameters. For pulsar timing arrays specifically, we interpolate over the parameter space of supermassive black-hole binary environments, including three-body stellar scattering, and evolving orbital eccentricity. We illustrate our approach on mock data, and assess the prospects for inference with data similar to the NANOGrav 9-yr data release.

Synthesis and in Vivo Evaluation of [123I]Melanin-Targeted Agents.

This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [(123)I]4 (ICF01012). The most favorable compounds ([(123)I]20, [(123)I]23, [(123)I]41, and [(123)I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [(123)I]20 and [(123)I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [(123)I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [(123)I]41 and [(123)I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [(123)I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [(131)I] therapeutic evaluation.

High-contrast PET of melanoma using (18)F-MEL050, a selective probe for melanin with predominantly renal clearance.

UNLABELLED: The aim of this study was to evaluate the novel probe (18)F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ((18)F-MEL050) for the imaging of primary and metastatic melanoma. METHODS: PET using (18)F-MEL050 was performed in murine models of melanoma. The specificity of (18)F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. (18)F-MEL050 PET results were compared with (18)F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of (18)F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. RESULTS: In pigmented B16-F0 grafts, (18)F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for (18)F-MEL050 than for (18)F-FDG (50.9 +/- 6.9 vs. 5.8 +/- 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of (18)F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor-bearing mice on PET at 2 h after tracer injection, with high concordance between (18)F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. CONCLUSION: (18)F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.

Discovery of [18F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide: a melanoma positron emission tomography imaging radiotracer with high tumor to body contrast ratio and rapid renal clearance.

The high melanoma uptake and rapid body clearance displayed by our series of [(123)I]iodonicotinamides prompted the development of [(18)F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide ([(18)F]2), a novel radiotracer for PET melanoma imaging. Significantly, unlike fluorobenzoates, [(18)F]fluorine incorporation on the nicotinamide ring is one step, facile, and high yielding. [(18)F]2 displayed high tumor uptake, rapid body clearance via predominantly renal excretion, and is currently being evaluated in preclinical studies for progression into clinical trials to assess the responsiveness of therapeutic agents.

SunSmart Plus": the more informed use of sunscreens.

The sun protection factor (SPF) of sunscreens is determined by a testing protocol that specifies a sunscreen application rate of 2 mg/cm(2) on the skin. Most people, for cosmetic and economic reasons, only apply enough sunscreen to achieve an SPF of about a third or even a quarter of the level stated on the product. To increase public awareness of the problem, manufacturers could be required to state both a "tested SPF" and an "expected SPF" (a third of the tested SPF) on product labelling. The "SunSmart" message could be modified to make the public more aware of the actual protection level they are achieving with sunscreen. Other aspects of the SunSmart message (eg, sun avoidance, wearing protective clothing) should also be reinforced.