Structural Diversity in Substituted Pyridinium Halocuprates(II)

The flexible coordination sphere of the Jahn-Teller active Cu(II) ion provides access to a full spectrum of coordination geometries from 4-coordinate (tetrahedral or square planar) to 6-coordinate elongated octahedral. This is further enhanced in anionic halide complexes by the ability of the halide ligand to bridge between Cu(II) centers to generate extended oligomeric or polymeric complexes. Coordination geometry and extended structure of the anionic complex is very sensitive to the nature of the organic counterion. This is especially true for planar substituted pyridinium cations in which minor changes in the nature or position of the substituted group can generate completely different halocuprate(II) structures. Early work focused on reducing ligand-ligand repulsion through strong hydrogen bonding with the organic cation in order to manipulate the Cu(II) coordination sphere. However, many unique structures have been found in which quaternary pyridinium cations were employed-including the remarkable thermochromic compound (1,2,6-trimethylpyridinium)2CuCl4- in which strong hydrogen bonding is absent. More recently aminopyridinium cations, which further increase structural diversity not only through the possibility of having mono- or di-protonated cations but also the ability of monoprotonated cations to coordinate to the Cu(II) center through the amino group, have been investigated

1,2-Diiodo-4,5-dimethyl­benzene

The structure of the title compound, C8H8I2, conforms closely to the mm2 symmetry expected for the free mol­ecule and is the first reported structure of a diiodo­dimethyl­benzene. Repulsion by neighboring I atoms and the neighboring methyl groups opposite to them results in a slight elongation of the mol­ecule along the approximate twofold rotation axis that bis­ects the ring between the two I atoms. In the extended structure, the mol­ecules form inversion-related pairs which are organized in approximately hexa­gonal close-packed layers and the layers then stacked so that mol­ecules in neighboring layers abut head-to-tail in a manner that optimizes dipole–dipole inter­actions

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

A Novel Method to Adjust Efficacy Estimates for Uptake of Other Active Treatments in Long-Term Clinical Trials

BACKGROUND: When rates of uptake of other drugs differ between treatment arms in long-term trials, the true benefit or harm of the treatment may be underestimated. Methods to allow for such contamination have often been limited by failing to preserve the randomization comparisons. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, patients were randomized to fenofibrate or placebo, but during the trial many started additional drugs, particularly statins, more so in the placebo group. The effects of fenofibrate estimated by intention-to-treat were likely to have been attenuated. We aimed to quantify this effect and to develop a method for use in other long-term trials. METHODOLOGY/PRINCIPAL FINDINGS: We applied efficacies of statins and other cardiovascular drugs from meta-analyses of randomized trials to adjust the effect of fenofibrate in a penalized Cox model. We assumed that future cardiovascular disease events were reduced by an average of 24% by statins, and 20% by a first other major cardiovascular drug. We applied these estimates to each patient who took these drugs for the period they were on them. We also adjusted the analysis by the rate of discontinuing fenofibrate. Among 4,900 placebo patients, average statin use was 16% over five years. Among 4,895 assigned fenofibrate, statin use was 8% and nonuse of fenofibrate was 10%. In placebo patients, use of cardiovascular drugs was 1% to 3% higher. Before adjustment, fenofibrate was associated with an 11% reduction in coronary events (coronary heart disease death or myocardial infarction) (P = 0.16) and an 11% reduction in cardiovascular disease events (P = 0.04). After adjustment, the effects of fenofibrate on coronary events and cardiovascular disease events were 16% (P = 0.06) and 15% (P = 0.008), respectively. CONCLUSIONS/SIGNIFICANCE: This novel application of a penalized Cox model for adjustment of a trial estimate of treatment efficacy incorporates evidence-based estimates for other therapies, preserves comparisons between the randomized groups, and is applicable to other long-term trials. In the FIELD study example, the effects of fenofibrate on the risks of coronary heart disease and cardiovascular disease events were underestimated by up to one-third in the original analysis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64783481

Epigenetic regulation of F2RL3 associates with myocardial infarction and platelet function

DNA hypomethylation at the F2RL3 (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. F2RL3 encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease. METHODS: We conducted multiple independent experiments to assess whether DNA hypomethylation at F2RL3 in response to smoking is associated with risk of myocardial infarction via changes to platelet reactivity. Using cohort data (N=3205), we explored the relationship between smoking, DNA hypomethylation at F2RL3, and myocardial infarction. We compared platelet reactivity in individuals with low versus high DNA methylation at F2RL3 (N=41). We used an in vitro model to explore the biological response of F2RL3 to cigarette smoke extract. Finally, a series of reporter constructs were used to investigate how differential methylation could impact F2RL3 gene expression. RESULTS: Observationally, DNA methylation at F2RL3 mediated an estimated 34% of the smoking effect on increased risk of myocardial infarction. An association between methylation group (low/high) and platelet reactivity was observed in response to PAR4 (protease-activated receptor 4) stimulation. In cells, cigarette smoke extract exposure was associated with a 4.9% to 9.3% reduction in DNA methylation at F2RL3 and a corresponding 1.7-(95% CI, 1.2–2.4, P=0.04) fold increase in F2RL3 mRNA. Results from reporter assays suggest the exon 2 region of F2RL3 may help control gene expression. CONCLUSIONS: Smoking-induced epigenetic DNA hypomethylation at F2RL3 appears to increase PAR4 expression with potential downstream consequences for platelet reactivity. Combined evidence here not only identifies F2RL3 DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing F2RL3 regulation in a similar manner

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary