Platinum(II) phosphonate complexes derived from endo-8-camphanylphosphonic acid

The reactions of cis-[PtCl₂L₂] [L = PPh₃, PMe₂Ph or L₂ = Ph₂P(CH₂)₂PPh₂ (dppe)] with endo-8-camphanylphosphonic acid (CamPO₃H₂) and Ag₂O in refluxing dichloromethane gave platinum(II) phosphonate complexes [Pt(O₃PCam)L₂]. The X-ray crystal structure of [Pt(O₃PCam)(PPh₃)₂]•₂CHCl₃ shows that the bulky camphanyl group, rather than being directed away from the platinum, is instead directed into a pocket formed by the Pt and the two PPh₃ ligands. This allows the O₃P–CH₂ group to have a preferred staggered conformation. The complexes were studied in detail by NMR spectroscopy, which demonstrates non-fluxional behaviour for the sterically bulky PPh₃ and dppe derivatives, which contain inequivalent phosphine ligands in their ³¹P NMR spectra. These findings are backed up by theoretical calculations on the PPh₃ and PPhMe₂ derivatives, which show, respectively, high and low energy barriers to rotation of the camphanyl group in the PPh₃ and PPhMe₂ complexes. The X-ray crystal structure of CamPO₃H₂ is also reported, and consists of hydrogen-bonded hexameric aggregates, which assemble to form a columnar structure containing hydrophilic phosphonic acid channels surrounded by a sheath of bulky, hydrophobic camphanyl groups

Carotid Atheroma Rupture Observed In Vivo and FSI-Predicted Stress Distribution Based on Pre-rupture Imaging

Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid–structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture

A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.

PurposeCabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.MethodsThis was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR).ResultsSixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa.ConclusionsDespite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib

Gold, power, protest: Digital and social media and protests against large-scale mining projects in Colombia

Colombia’s Internet connectivity has increased immensely. Colombia has also ‘opened for business’, leading to an influx of extractive projects to which social movements object heavily. Studies on the role of digital media in political mobilisation in developing countries are still scarce. Using surveys, interviews, and reviews of literature, policy papers, website and social media content, this study examines the role of digital and social media in social movement organisations and asks how increased digital connectivity can help spread knowledge and mobilise mining protests. Results show that the use of new media in Colombia is hindered by socioeconomic constraints, fear of oppression, the constraints of keyboard activism and strong hierarchical power structures within social movements. Hence, effects on political mobilisation are still limited. Social media do not spontaneously produce non-hierarchical knowledge structures. Attention to both internal and external knowledge sharing is therefore conditional to optimising digital and social media use

Estimating the Location and Spatial Extent of a Covert Anthrax Release

Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. A back-calculation method is developed allowing the characterization of the release based on the data on the first few observed cases of the subsequent outbreak, meteorological data, population densities, and data on population travel patterns. We evaluate this method on small simulated anthrax outbreaks (about 25–35 cases) and show that it could date and localize a release after a few cases have been observed, although misspecifications of the spore dispersion model, or the within-host dynamics model, on which the method relies can bias the estimates. Our method could also provide an estimate of the outbreak's geographical extent and, as a consequence, could help to identify populations at risk and, therefore, requiring prophylactic treatment. Our analysis demonstrates that while estimates based on the first ten or 15 observed cases were more accurate and less sensitive to model misspecifications than those based on five cases, overall mortality is minimized by targeting prophylactic treatment early on the basis of estimates made using data on the first five cases. The method we propose could provide early estimates of the time, strength, and location of an aerosolized anthrax release and the geographical extent of the subsequent outbreak. In addition, estimates of release features could be used to parameterize more detailed models allowing the simulation of control strategies and intervention logistics

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

RITUAL, TIME, AND ENTERNITY

It is argued here that the construction of time and eternity are among ritual's entailments. In dividing continuous duration into distinct periods ritual distinguishes two temporal conditions: (1) that prevailing in mundane periods and (2) that prevailing during the intervals between them. Differences in the frequency, length, and relationship among the rituals constituting different liturgical orders are considered, as are differences between mundane periods and ritual's intervals with respect to social relations, cognitive modes, meaningfulness, and typical interactive frequencies. Periods, it is observed, relate to intervals as everchanging to never-changing, and close relationships of never changing to eternity, eternity to sanctity, and sanctity to truth are proposed. In the argument that ritual's “times out of time” really are outside mundane time, similarities to the operations of digital computers and Herbert Simon's discussion of interaction frequencies in the organization of matter are noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72989/1/j.1467-9744.1992.tb00996.x.pd

ASKAP HI imaging of the galaxy group IC 1459

© 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. We present HI imaging of the galaxy group IC 1459 carried out with six antennas of the Australian Square Kilometre Array Pathfinder equipped with phased-array feeds. We detect and resolve HI in 11 galaxies down to a column density of ~1020 cm-2 inside a ~6 deg2 field and with a resolution of ~1 arcmin on the sky and ~8 kms-1 in velocity. We present HI images, velocity fields and integrated spectra of all detections, and highlight the discovery of three HI clouds - two in the proximity of the galaxy IC 5270 and one close to NGC 7418. Each cloud has an HI mass of ~109 M? and accounts for ~15 per cent of the HI associated with its host galaxy. Available images at ultraviolet, optical and infrared wavelengths do not reveal any clear stellar counterpart of any of the clouds, suggesting that they are not gas-rich dwarf neighbours of IC 5270 and NGC 7418. Using Parkes data, we find evidence of additional extended, low-column-density HI emission around IC 5270, indicating that the clouds are the tip of the iceberg of a larger system of gas surrounding this galaxy. This result adds to the body of evidence on the presence of intragroup gas within the IC 1459 group. Altogether, the HI found outside galaxies in this group amounts to several times 109 M?, at least 10 per cent of the HI contained inside galaxies. This suggests a substantial flow of gas in and out of galaxies during the several billion years of the group's evolution